The virus–receptor interaction in the replication of feline immunodeficiency virus (FIV)☆

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Willett, Brian J; Hosie, Margaret J

2013-01-01

The feline and human immunodeficiency viruses (FIV and HIV) target helper T cells selectively, and in doing so they induce a profound immune dysfunction. The primary determinant of HIV cell tropism is the expression pattern of the primary viral receptor CD4 and co-receptor(s), such as CXCR4 and CCR5. FIV employs a distinct strategy to target helper T cells; a high affinity interaction with CD134 (OX40) is followed by binding of the virus to its sole co-receptor, CXCR4. Recent studies have demonstrated that the way in which FIV interacts with its primary receptor, CD134, alters as infection progresses, changing the cell tropism of the virus. This review examines the contribution of the virus–receptor interaction to replication in vivo as well as the significance of these findings to the development of vaccines and therapeutics. PMID:23992667

A Naturally Occurring Domestic Cat APOBEC3 Variant Confers Resistance to Feline Immunodeficiency Virus Infection.

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Yoshikawa, Rokusuke; Izumi, Taisuke; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Ren, Fengrong; Carpenter, Michael A; Ikeda, Terumasa; Münk, Carsten; Harris, Reuben S; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei

2016-01-01

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) DNA cytosine deaminases can be incorporated into progeny virions and inhibit lentiviral replication. On the other hand, viral infectivity factor (Vif) of lentiviruses antagonizes A3-mediated antiviral activities by degrading A3 proteins. It is known that domestic cat (Felis catus) APOBEC3Z3 (A3Z3), the ortholog of human APOBEC3H, potently suppresses the infectivity of vif-defective feline immunodeficiency virus (FIV). Although a recent report has shown that domestic cat encodes 7 haplotypes (hap I to hap VII) of A3Z3, the relevance of A3Z3 polymorphism in domestic cats with FIV Vif has not yet been addressed. In this study, we demonstrated that these feline A3Z3 variants suppress vif-defective FIV infectivity. We also revealed that codon 65 of feline A3Z3 is a positively selected site and that A3Z3 hap V is subject to positive selection during evolution. It is particularly noteworthy that feline A3Z3 hap V is resistant to FIV Vif-mediated degradation and still inhibits vif-proficient viral infection. Moreover, the side chain size, but not the hydrophobicity, of the amino acid at position 65 determines the resistance to FIV Vif-mediated degradation. Furthermore, phylogenetic analyses have led to the inference that feline A3Z3 hap V emerged approximately 60,000 years ago. Taken together, these findings suggest that feline A3Z3 hap V may have been selected for escape from an ancestral FIV. This is the first evidence for an evolutionary "arms race" between the domestic cat and its cognate lentivirus. Gene diversity and selective pressure are intriguing topics in the field of evolutionary biology. A direct interaction between a cellular protein and a viral protein can precipitate an evolutionary arms race between host and virus. One example is primate APOBEC3G, which potently restricts the replication of primate lentiviruses (e.g., human immunodeficiency virus type 1 [HIV-1] and simian

Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

OpenAIRE

Jiae Kim; Jiae Kim; Kristina K. Peachman; Kristina K. Peachman; Ousman Jobe; Ousman Jobe; Elaine B. Morrison; Atef Allam; Atef Allam; Linda Jagodzinski; Sofia A. Casares; Mangala Rao

2017-01-01

Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP) models for studying human immunodeficiency virus (HIV)-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several...

Cellular Restriction Factors of Feline Immunodeficiency Virus

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Zielonka, Jörg; Münk, Carsten

2011-01-01

Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating. Of particular importance are the cellular proteins APOBEC3, TRIM5α and tetherin/BST-2. In general, lentiviruses counteract or escape their species’ own variant of the restriction factor, but are targeted by the orthologous proteins of distantly related species. Most of the knowledge regarding lentiviral restriction factors has been obtained in the HIV-1 system; however, much less is known about their effects on other lentiviruses. We describe here the molecular mechanisms that explain how FIV maintains its replication in feline cells, but is largely prevented from cross-species infections by cellular restriction factors. PMID:22069525

The impact of early immune destruction on the kinetics of postacute viral replication in rhesus monkey infected with the simian-human immunodeficiency virus 89.6P

International Nuclear Information System (INIS)

Zhang Zhiqiang; Schleif, William A.; Casimiro, Danilo R.; Handt, Larry; Chen, Minchun; Davies, Mary-Ellen; Liang Xiaoping; Fu Tongming; Tang Aimin; Wilson, Keith A.; McElhaugh, Michael; Carella, Anthony; Tan, Charles; Connolly, Brett; Hill, Susan; Klein, Hilton; Emini, Emilio A.; Shiver, John W.

2004-01-01

Set-point viral load is positively correlated with the extent of initial viral replication in pathogenic simian-human immunodeficiency virus (SHIV) infection. To elucidate the mechanisms underlying the correlation, we conducted a systematic investigation in rhesus monkeys infected with the highly pathogenic SHIV 89.6P. This model is widely used in the preclinical evaluation of AIDS vaccine candidates and a thorough understanding of the model's biology is important to the proper interpretation of these evaluations. We found that the levels of peak viremia were positively correlated not only with the levels of set-point viremia but, importantly, with the extent of initial overall immune destruction as indicated by the degree of CD4 + T cell depletion and lymph node germinal center (GC) formation. The extent of initial overall immune destruction was inversely correlated with subsequent development and maintenance of virus-specific cellular and humoral immune responses. Thus, these data suggest that the extent of early immune damage determines the development and durability of virus-specific immunity, thereby playing a critical role in establishing the levels of set-point viral replication in SHIV infection. Vaccines that limit both the initial viral replication and the extent of early immune damage will therefore mediate long-term virus replication control and mitigation of long-term immune destruction in this model of immunodeficiency virus infection

Cyclin A degradation by primate cytomegalovirus protein pUL21a counters its innate restriction of virus replication.

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Nicolas Caffarelli

Full Text Available Cyclin A is critical for cellular DNA synthesis and S phase progression of the cell cycle. Human cytomegalovirus (HCMV can reduce cyclin A levels and block cellular DNA synthesis, and cyclin A overexpression can repress HCMV replication. This interaction has only been previously observed in HCMV as murine CMV does not downregulate cyclin A, and the responsible viral factor has not been identified. We previously reported that the HCMV protein pUL21a disrupted the anaphase-promoting complex (APC, but a point mutant abrogating this activity did not phenocopy a UL21a-deficient virus, suggesting that pUL21a has an additional function. Here we identified a conserved arginine-x-leucine (RxL cyclin-binding domain within pUL21a, which allowed pUL21a to interact with cyclin A and target it for proteasome degradation. Homologous pUL21a proteins from both chimpanzee and rhesus CMVs also contained the RxL domain and similarly degraded cyclin A, indicating that this function is conserved in primate CMVs. The RxL point mutation disabled the virus' ability to block cellular DNA synthesis and resulted in a growth defect similar to pUL21a-deficient virus. Importantly, knockdown of cyclin A rescued growth of UL21a-deficient virus. Together, these data show that during evolution, the pUL21a family proteins of primate CMVs have acquired a cyclin-binding domain that targets cyclin A for degradation, thus neutralizing its restriction on virus replication. Finally, the combined proteasome-dependent degradation of pUL21a and its cellular targets suggests that pUL21a may act as a novel suicide protein, targeting its protein cargos for destruction.

Functions of alternative Replication Protein A (aRPA) in initiation and elongation

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Mason, Aaron C.; Roy, Rupa; Simmons, Daniel T.; Wold, Marc S.

2010-01-01

Replication protein A (RPA) is a single-stranded DNA-binding complex that is essential for DNA replication, repair and recombination in eukaryotic cells. In addition to this canonical complex, we have recently characterized an alternative Replication Protein A complex (aRPA) that is unique to primates. aRPA is composed of three subunits: RPA1 and RPA3, also present in canonical RPA, and a primate-specific subunit RPA4, homologous to canonical RPA2. aRPA has biochemical properties similar to t...

Nonhuman Primate Models of Hepatitis A Virus and Hepatitis E Virus Infections.

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Lanford, Robert E; Walker, Christopher M; Lemon, Stanley M

2018-04-23

Although phylogenetically unrelated, human hepatitis viruses share an exclusive or near exclusive tropism for replication in differentiated hepatocytes. This narrow tissue tropism may contribute to the restriction of the host ranges of these viruses to relatively few host species, mostly nonhuman primates. Nonhuman primate models thus figure prominently in our current understanding of the replication and pathogenesis of these viruses, including the enterically transmitted hepatitis A virus (HAV) and hepatitis E virus (HEV), and have also played major roles in vaccine development. This review draws comparisons of HAV and HEV infection from studies conducted in nonhuman primates, and describes how such studies have contributed to our current understanding of the biology of these viruses. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Identifying recombinants in human and primate immunodeficiency virus sequence alignments using quartet scanning

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Martin Darren P

2009-04-01

Full Text Available Abstract Background Recombination has a profound impact on the evolution of viruses, but characterizing recombination patterns in molecular sequences remains a challenging endeavor. Despite its importance in molecular evolutionary studies, identifying the sequences that exhibit such patterns has received comparatively less attention in the recombination detection framework. Here, we extend a quartet-mapping based recombination detection method to enable identification of recombinant sequences without prior specifications of either query and reference sequences. Through simulations we evaluate different recombinant identification statistics and significance tests. We compare the quartet approach with triplet-based methods that employ additional heuristic tests to identify parental and recombinant sequences. Results Analysis of phylogenetic simulations reveal that identifying the descendents of relatively old recombination events is a challenging task for all methods available, and that quartet scanning performs relatively well compared to the triplet based methods. The use of quartet scanning is further demonstrated by analyzing both well-established and putative HIV-1 recombinant strains. In agreement with recent findings, we provide evidence that the presumed circulating recombinant CRF02_AG is a 'pure' lineage, whereas the presumed parental lineage subtype G has a recombinant origin. We also demonstrate HIV-1 intrasubtype recombination, confirm the hybrid origin of SIV in chimpanzees and further disentangle the recombinant history of SIV lineages in a primate immunodeficiency virus data set. Conclusion Quartet scanning makes a valuable addition to triplet-based methods for identifying recombinant sequences without prior specifications of either query and reference sequences. The new method is available in the VisRD v.3.0 package http://www.cmp.uea.ac.uk/~vlm/visrd.

Cellular Restriction Factors of Feline Immunodeficiency Virus

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Carsten Münk

2011-10-01

Full Text Available Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors or inhibit viral replication (restriction factors. Similar to Human immunodeficiency virus type 1 (HIV-1, the cat lentivirus Feline immunodeficiency virus (FIV is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating. Of particular importance are the cellular proteins APOBEC3, TRIM5α and tetherin/BST-2. In general, lentiviruses counteract or escape their species’ own variant of the restriction factor, but are targeted by the orthologous proteins of distantly related species. Most of the knowledge regarding lentiviral restriction factors has been obtained in the HIV-1 system; however, much less is known about their effects on other lentiviruses. We describe here the molecular mechanisms that explain how FIV maintains its replication in feline cells, but is largely prevented from cross-species infections by cellular restriction factors.

Intrinsic Stability of Episomal Circles Formed during Human Immunodeficiency Virus Type 1 Replication

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Pierson, TheodoreC.; Kieffer, Tara L.; Ruff, Christian T.; Buck, Christopher; Gange, Stephen J.; Siliciano, Robert F.

2002-01-01

The development of surrogate markers capable of detecting residual ongoing human immunodeficiency virus type 1 (HIV-1) replication in patients receiving highly active antiretroviral therapy is an important step in understanding viral dynamics and in developing new treatment strategies. In this study, we evaluated the utility of circular forms of the viral genome for the detection of recent infection of cells by HIV-1. We measured the fate of both one-long terminal repeat (1-LTR) and 2-LTR circles following in vitro infection of logarithmically growing CD4+ T cells under conditions in which cell death was not a significant contributing factor. Circular forms of the viral genome were found to be highly stable and to decrease in concentration only as a function of dilution resulting from cell division. We conclude that these DNA circles are not intrinsically unstable in all cell types and suggest that the utility of 2-LTR circle assays in measuring recent HIV-1 infection of susceptible cells in vivo needs to be reevaluated. PMID:11907256

Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines

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Kuate, Seraphin; Stahl-Hennig, Christiane; Haaft, Peter ten; Heeney, Jonathan; Ueberla, Klaus

2003-01-01

To reduce the risks associated with live-attenuated immunodeficiency virus vaccines, single-cycle immunodeficiency viruses (SCIVs) were developed by primer complementation and production of the vaccine in the absence of vif in a vif-independent cell line. After a single intravenous injection of SCIVs into rhesus monkeys, peak viral RNA levels of 10 3 to 10 4 copies/ml plasma were observed, indicating efficient expression of SCIV in the vaccinee. After booster immunizations with SCIVs, SIV-specific humoral and cellular immune responses were observed. Although the vaccine doses used in this pilot study could not protect vaccinees from subsequent intravenous challenge with pathogenic SIVmac239, our results demonstrate that the novel SCIV approach allows us to uncouple in vivo expression levels from the viral replicative capacity facilitating the analysis of the relationship between viral expression levels or viral genes and immune responses induced by SIV

Comparative Immunogenicity in Rhesus Monkeys of DNA Plasmid, Recombinant Vaccinia Virus, and Replication-Defective Adenovirus Vectors Expressing a Human Immunodeficiency Virus Type 1 gag Gene

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Casimiro, Danilo R.; Chen, Ling; Fu, Tong-Ming; Evans, Robert K.; Caulfield, Michael J.; Davies, Mary-Ellen; Tang, Aimin; Chen, Minchun; Huang, Lingyi; Harris, Virginia; Freed, Daniel C.; Wilson, Keith A.; Dubey, Sheri; Zhu, De-Min; Nawrocki, Denise

2003-01-01

Cellular immune responses, particularly those associated with CD3+ CD8+ cytotoxic T lymphocytes (CTL), play a primary role in controlling viral infection, including persistent infection with human immunodeficiency virus type 1 (HIV-1). Accordingly, recent HIV-1 vaccine research efforts have focused on establishing the optimal means of eliciting such antiviral CTL immune responses. We evaluated several DNA vaccine formulations, a modified vaccinia virus Ankara vector, and a replication-defecti...

Pharmacological inhibition of feline immunodeficiency virus (FIV).

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Mohammadi, Hakimeh; Bienzle, Dorothee

2012-05-01

Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS) in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1) inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus membrane with the cell membrane; (3) blockade of reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and viral DNA integration into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats.

Evolutionary and Functional Analysis of Old World Primate TRIM5 Reveals the Ancient Emergence of Primate Lentiviruses and Convergent Evolution Targeting a Conserved Capsid Interface.

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Kevin R McCarthy

2015-08-01

Full Text Available The widespread distribution of lentiviruses among African primates, and the lack of severe pathogenesis in many of these natural reservoirs, are taken as evidence for long-term co-evolution between the simian immunodeficiency viruses (SIVs and their primate hosts. Evidence for positive selection acting on antiviral restriction factors is consistent with virus-host interactions spanning millions of years of primate evolution. However, many restriction mechanisms are not virus-specific, and selection cannot be unambiguously attributed to any one type of virus. We hypothesized that the restriction factor TRIM5, because of its unique specificity for retrovirus capsids, should accumulate adaptive changes in a virus-specific fashion, and therefore, that phylogenetic reconstruction of TRIM5 evolution in African primates should reveal selection by lentiviruses closely related to modern SIVs. We analyzed complete TRIM5 coding sequences of 22 Old World primates and identified a tightly-spaced cluster of branch-specific adaptions appearing in the Cercopithecinae lineage after divergence from the Colobinae around 16 million years ago. Functional assays of both extant TRIM5 orthologs and reconstructed ancestral TRIM5 proteins revealed that this cluster of adaptations in TRIM5 specifically resulted in the ability to restrict Cercopithecine lentiviruses, but had no effect (positive or negative on restriction of other retroviruses, including lentiviruses of non-Cercopithecine primates. The correlation between lineage-specific adaptations and ability to restrict viruses endemic to the same hosts supports the hypothesis that lentiviruses closely related to modern SIVs were present in Africa and infecting the ancestors of Cercopithecine primates as far back as 16 million years ago, and provides insight into the evolution of TRIM5 specificity.

Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication

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Watanabe, Mamoru; Chen, Zheng W.; Tsubota, Hiroshi; Lord, C.I.; Levine, C.G.; Letvin, N.L.

1991-01-01

Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIV mac ) demonstrate significant virologic and clinical improvement as a result of treatment with human recombinant soluble CD4 (rsCD4). The authors show that human rsCD4 does not efficiently inhibit SIV mac replication in bone marrow macrophages of rhesus monkeys and does not significantly augment bone marrow hematopoietic colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys does exhibit significant anti-SIV mac activity in vitro. Plasma of these animals efficiently blocks SIV mac replicaton in peripheral blood lymphocytes and bone marrow macrophages. It also increases granulocyte/macrophage colony formation in vitro by bone marrow cells of SIV mac -infected monkeys. This plasma and the IgG fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule, exhibit binding to CD4 + but not CD8 + concanavalin A-activated rhesus monkey peripheral blood lymphocytes, and precipitate the CD4 molecule from surface-labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti-viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4-immunized monkey. These studies raise the possibility that a modified human CD4 molecule serving as an immunogen might elicit an antibody response that could potentially induce a beneficial therapeutic response in human immunodeficiency virus-infected individuals

Replicating rather than nonreplicating adenovirus-human immunodeficiency virus recombinant vaccines are better at eliciting potent cellular immunity and priming high-titer antibodies.

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Peng, Bo; Wang, Liqun Rejean; Gómez-Román, Victor Raúl; Davis-Warren, Alberta; Montefiori, David C; Kalyanaraman, V S; Venzon, David; Zhao, Jun; Kan, Elaine; Rowell, Thomas J; Murthy, Krishna K; Srivastava, Indresh; Barnett, Susan W; Robert-Guroff, Marjorie

2005-08-01

A major challenge in combating the human immunodeficiency virus (HIV) epidemic is the development of vaccines capable of inducing potent, persistent cellular immunity and broadly reactive neutralizing antibody responses to HIV type 1 (HIV-1). We report here the results of a preclinical trial using the chimpanzee model to investigate a combination vaccine strategy involving sequential priming immunizations with different serotypes of adenovirus (Ad)/HIV-1(MN)env/rev recombinants and boosting with an HIV envelope subunit protein, oligomeric HIV(SF162) gp140deltaV2. The immunogenicities of replicating and nonreplicating Ad/HIV-1(MN)env/rev recombinants were compared. Replicating Ad/HIV recombinants were better at eliciting HIV-specific cellular immune responses and better at priming humoral immunity against HIV than nonreplicating Ad-HIV recombinants carrying the same gene insert. Enhanced cellular immunity was manifested by a greater frequency of HIV envelope-specific gamma interferon-secreting peripheral blood lymphocytes and better priming of T-cell proliferative responses. Enhanced humoral immunity was seen in higher anti-envelope binding and neutralizing antibody titers and better induction of antibody-dependent cellular cytotoxicity. More animals primed with replicating Ad recombinants mounted neutralizing antibodies against heterologous R5 viruses after one or two booster immunizations with the mismatched oligomeric HIV-1(SF162) gp140deltaV2 protein. These results support continued development of the replicating Ad-HIV recombinant vaccine approach and suggest that the use of replicating vectors for other vaccines may prove fruitful.

Pharmacological Inhibition of Feline Immunodeficiency Virus (FIV

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Dorothee Bienzle

2012-04-01

Full Text Available Feline immunodeficiency virus (FIV is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV. Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1 inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2 inhibition of fusion of the virus membrane with the cell membrane; (3 blockade of reverse transcription of viral genomic RNA; (4 interruption of nuclear translocation and viral DNA integration into host genomes; (5 prevention of viral transcript processing and nuclear export; and (6 inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats.

Simian Immunodeficiency Virus (SIV-Specific Chimeric Antigen Receptor-T Cells Engineered to Target B Cell Follicles and Suppress SIV Replication

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Kumudhini Preethi Haran

2018-03-01

Full Text Available There is a need to develop improved methods to treat and potentially cure HIV infection. During chronic HIV infection, replication is concentrated within T follicular helper cells (Tfh located within B cell follicles, where low levels of virus-specific CTL permit ongoing viral replication. We previously showed that elevated levels of simian immunodeficiency virus (SIV-specific CTL in B cell follicles are linked to both decreased levels of viral replication in follicles and decreased plasma viral loads. These findings provide the rationale to develop a strategy for targeting follicular viral-producing (Tfh cells using antiviral chimeric antigen receptor (CAR T cells co-expressing the follicular homing chemokine receptor CXCR5. We hypothesize that antiviral CAR/CXCR5-expressing T cells, when infused into an SIV-infected animal or an HIV-infected individual, will home to B cell follicles, suppress viral replication, and lead to long-term durable remission of SIV and HIV. To begin to test this hypothesis, we engineered gammaretroviral transduction vectors for co-expression of a bispecific anti-SIV CAR and rhesus macaque CXCR5. Viral suppression by CAR/CXCR5-transduced T cells was measured in vitro, and CXCR5-mediated migration was evaluated using both an in vitro transwell migration assay, as well as a novel ex vivo tissue migration assay. The functionality of the CAR/CXCR5 T cells was demonstrated through their potent suppression of SIVmac239 and SIVE660 replication in in vitro and migration to the ligand CXCL13 in vitro, and concentration in B cell follicles in tissues ex vivo. These novel antiviral immunotherapy products have the potential to provide long-term durable remission (functional cure of HIV and SIV infections.

Vaccines. An Ebola whole-virus vaccine is protective in nonhuman primates.

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Marzi, Andrea; Halfmann, Peter; Hill-Batorski, Lindsay; Feldmann, Friederike; Shupert, W Lesley; Neumann, Gabriele; Feldmann, Heinz; Kawaoka, Yoshihiro

2015-04-24

Zaire ebolavirus is the causative agent of the current outbreak of hemorrhagic fever disease in West Africa. Previously, we showed that a whole Ebola virus (EBOV) vaccine based on a replication-defective EBOV (EBOVΔVP30) protects immunized mice and guinea pigs against lethal challenge with rodent-adapted EBOV. Here, we demonstrate that EBOVΔVP30 protects nonhuman primates against lethal infection with EBOV. Although EBOVΔVP30 is replication-incompetent, we additionally inactivated the vaccine with hydrogen peroxide; the chemically inactivated vaccine remained antigenic and protective in nonhuman primates. EBOVΔVP30 thus represents a safe, efficacious, whole-EBOV vaccine candidate that differs from other EBOV vaccine platforms in that it presents all viral proteins and the viral RNA to the host immune system, which might contribute to protective immune responses. Copyright © 2015, American Association for the Advancement of Science.

Genotyping of TRIM5 locus in northern pig-tailed macaques (Macaca leonina, a primate species susceptible to Human Immunodeficiency Virus type 1 infection

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Jiang Xue-Long

2009-06-01

Full Text Available Abstract Background The pig-tailed macaques are the only Old World monkeys known to be susceptible to human immunodeficiency virus type 1 (HIV-1 infection. We have previously reported that the TRIM5-Cyclophilin A (TRIMCyp fusion in pig-tailed macaques (Macaca nemestrina is dysfunctional in restricting HIV-1, which may explain why pig-tailed macaques are susceptible to HIV-1 infection. Similar results have also been reported by other groups. However, according to the current primate taxonomy, the previously reported M. nemestrina are further classified into three species, which all belong to the Macaca spp. This calls for the need to look into the previous studies in more details. Results The local species Northern pig-tailed macaque (M. leonina was analyzed for the correlation of TRIM5 structure and HIV-1 infection. Eleven M. leonina animals were analyzed, and all of them were found to possess TRIM5-CypA fusion at the TRIM5 locus. The transcripts encoding the dysfunctional TRIM5-CypA should result from the G-to-T mutation in the 3'-splicing site of intron 6. Polymorphism in the putative TRIMCyp recognition domain was observed. The peripheral blood mononuclear cells (PBMCs of M. leonina were susceptible to HIV-1 infection. Consistent with the previous results, expression of the M. leonina TRIMCyp in HeLa-T4 cells rendered the cells resistant to HIV-2ROD but not to SIVmac239 infection. Conclusion The susceptibility of M. leonina to HIV-1 infection is due to the dysfunctional TRIM5-CypA fusion in the TRIM5 locus. This finding should broaden our perspective in developing better HIV/AIDS non-human primate animal models.

Replication-dependent 65R→K reversion in human immunodeficiency virus type 1 reverse transcriptase double mutant K65R + L74V

International Nuclear Information System (INIS)

Sharma, Prem L.; Nurpeisov, Viktoria; Lee, Kimberly; Skaggs, Sara; Di San Filippo, Christina Amat; Schinazi, Raymond F.

2004-01-01

Understanding of the mechanisms of interaction among nucleoside reverse transcriptase inhibitor (NRTI)-selected mutations in the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) coding sequence is essential for the design of newer drugs and for enhancing our vision of the structure function relationship among amino acids of the polymerase domain of HIV-1. Although several nucleoside reverse transcriptase inhibitors select RT mutations K65R and L74V, the combination of 65R + 74V is rare in clinics. A novel NRTI (-)-β-D-dioxolane-guanosine (DXG) is known to select in vitro either the 65R or 74V mutant virus (Antimicrob. Agents Chemother. 44 (2000) 1783). These mutations were not selected together during repeated passaging of the HIV-1 in the presence of this drug. To analyze the impact of these RT mutations on viral replication, a double mutant containing K65R + L74V was created by site-directed mutagenesis in a pNL4-3 background. Replication kinetic assays revealed that the mutant K65R + L74V is unstable, and 65R→K reversion occurs during replication of virus in phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear (PBM) cells in the absence of selection pressure. Replication kinetic assays in MT-2 cells demonstrated that double mutant 65R + 74V is highly attenuated for replication and the initiation of reversion is related to the increase in RT activity. Additionally, the suppression of viral replication in the presence of DXG or under suboptimal human recombinant interleukin-2 leads to minimal or no 65R→K reversion. These observations provide evidence that 65R→K reversion in the double mutant 65R + 74V is dependent on a specific rate of viral replication in a pNL4-3 background. A similar phenomenon may occur in vivo, which may have implications for treatment management strategies

Spatial analysis of feline immunodeficiency virus infection in cougars.

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Wheeler, David C; Waller, Lance A; Biek, Roman

2010-07-01

The cougar (Puma concolor) is a large predatory feline found widely in the Americas that is susceptible to feline immunodeficiency virus (FIV), a fast-evolving lentivirus found in wild feline species that is analogous to simian immunodeficiency viruses in wild primates and belongs to the same family of viruses as human immunodeficiency virus. FIV infection in cougars can lead to a weakened immune system that creates opportunities for other infecting agents. FIV prevalence and lineages have been studied previously in several areas in the western United States, but typically without spatially explicit statistical techniques. To describe the distribution of FIV in a sample of cougars located in the northern Rocky Mountain region of North America, we first used kernel density ratio estimation to map the log relative risk of FIV. The risk surface showed a significant cluster of FIV in northwestern Montana. We also used Bayesian cluster models for genetic data to investigate the spatial structure of the feline immunodeficiency virus with virus genetic sequence data. A result of the models was two spatially distinct FIV lineages that aligned considerably with an interstate highway in Montana. Our results suggest that the use of spatial information and models adds novel insight when investigating an infectious animal disease. The results also suggest that the influence of landscape features likely plays an important role in the spatiotemporal spread of an infectious disease within wildlife populations.

High throughput generation and characterization of replication-competent clade C transmitter-founder simian human immunodeficiency viruses.

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Debashis Dutta

Full Text Available Traditional restriction endonuclease-based cloning has been routinely used to generate replication-competent simian-human immunodeficiency viruses (SHIV and simian tropic HIV (stHIV. This approach requires the existence of suitable restriction sites or the introduction of nucleotide changes to create them. Here, using an In-Fusion cloning technique that involves homologous recombination, we generated SHIVs and stHIVs based on epidemiologically linked clade C transmitted/founder HIV molecular clones from Zambia. Replacing vif from these HIV molecular clones with vif of SIVmac239 resulted in chimeric genomes used to generate infectious stHIV viruses. Likewise, exchanging HIV env genes and introducing N375 mutations to enhance macaque CD4 binding site and cloned into a SHIVAD8-EO backbone. The generated SHIVs and stHIV were infectious in TZMbl and ZB5 cells, as well as macaque PBMCs. Therefore, this method can replace traditional methods and be a valuable tool for the rapid generation and testing of molecular clones of stHIV and SHIV based on primary clinical isolates will be valuable to generate rapid novel challenge viruses for HIV vaccine/cure studies.

Exosomes from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells License Quiescent CD4+ T Lymphocytes To Replicate HIV-1 through a Nef- and ADAM17-Dependent Mechanism

OpenAIRE

Arenaccio, Claudia; Chiozzini, Chiara; Columba-Cabezas, Sandra; Manfredi, Francesco; Affabris, Elisabetta; Baur, Andreas; Federico, Maurizio

2014-01-01

Resting CD4+ T lymphocytes resist human immunodeficiency virus (HIV) infection. Here, we provide evidence that exosomes from HIV-1-infected cells render resting human primary CD4+ T lymphocytes permissive to HIV-1 replication. These results were obtained with transwell cocultures of HIV-1-infected cells with quiescent CD4+ T lymphocytes in the presence of inhibitors of exosome release and were confirmed using exosomes purified from supernatants of HIV-1-infected primary CD4+ T lymphocytes. We...

A brief history of the discovery of natural simian immunodeficiency virus (SIV) infections in captive sooty mangabey monkeys.

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Gormus, Bobby J; Martin, Louis N; Baskin, Gary B

2004-01-01

Experimental leprosy studies using Mycobacterium leprae inoculum isolated from a sooty mangabey monkey (SMM) resulted in the accidental discovery that SMM's asymptomatically carry simian immunodeficiency virus (SIV) that is pathogenic in macaques. We showed that the SMM virus, SIVDelta, was antigenically related to SIVmac, which had been identified in macaques, and to the human immunodeficiency virus (HIV). Similar asymptomatic natural SIV infections had been reported in African green monkeys (AGM). Our results together with observations of others led us to propose that both SIVmac and SIVDelta originated in SMM and that SIV emerged in humans as a result of early African nonhuman primate SIV trans-species infections in humans.

Effects of integration and replication on transcription of the HIV-1 long terminal repeat

NARCIS (Netherlands)

Jeang, K. T.; Berkhout, B.; Dropulic, B.

1993-01-01

The activity of a promoter is influenced by chromosomal and cell cycle/replication context. We analyzed the influences of integration and replication on transcription of the human immunodeficiency virus (HIV)-1 long terminal repeat (LTR). We found that one requirement for Tat trans-activated

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review.

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Eckstrand, Chrissy D; Sparger, Ellen E; Murphy, Brian G

2017-08-01

Infection with feline immunodeficiency virus (FIV), a lentivirus similar to human immunodeficiency virus (HIV), results in lifelong viral persistence and progressive immunopathology in the cat. FIV has the ability to infect and produce infectious virus in a number of different cell types. FIV provirus can also be maintained in a replication-competent but transcriptionally quiescent state, facilitating viral persistence over time. Immediately after the initial infection, FIV infection quickly disseminates to many anatomical compartments within the host including lymphoid organs, gastrointestinal tract and brain. Collectively, the anatomic and cellular compartments that harbour FIV provirus constitute the viral reservoir and contain foci of both ongoing viral replication and transcriptionally restricted virus that may persist over time. The relative importance of the different phenotypes observed for infected cells, anatomic compartment, replication status and size of the reservoir represent crucial areas of investigation for developing effective viral suppression and eradication therapies. In this review, we discuss what is currently known about FIV reservoirs, and emphasize the utility of the FIV-infected cat as a model for the HIV-infected human.

Mechanism of feline immunodeficiency virus envelope glycoprotein-mediated fusion

International Nuclear Information System (INIS)

Garg, Himanshu; Fuller, Frederick J.; Tompkins, Wayne A.F.

2004-01-01

Feline immunodeficiency virus (FIV) shares remarkable homology to primate lentiviruses, human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). The process of lentiviral env glycoprotein-mediated fusion of membranes is essential for viral entry and syncytia formation. A detailed understanding of this phenomenon has helped identify new targets for antiviral drug development. Using a model based on syncytia formation between FIV env-expressing cells and a feline CD4+ T cell line we have studied the mechanism of FIV env-mediated fusion. Using this model we show that FIV env-mediated fusion mechanism and kinetics are similar to HIV env. Syncytia formation could be blocked by CXCR4 antagonist AMD3100, establishing the importance of this receptor in FIV gp120 binding. Interestingly, CXCR4 alone was not sufficient to allow fusion by a primary isolate of FIV, as env glycoprotein from FIV-NCSU 1 failed to induce syncytia in several feline cell lines expressing CXCR4. Syncytia formation could be inhibited at a post-CXCR4 binding step by synthetic peptide T1971, which inhibits interaction of heptad repeat regions of gp41 and formation of the hairpin structure. Finally, using site-directed mutagenesis, we also show that a conserved tryptophan-rich region in the membrane proximal ectodomain of gp41 is critical for fusion, possibly at steps post hairpin structure formation

Replicative senescence of T cells: does the Hayflick Limit lead to immune exhaustion?

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Effros, R B; Pawelec, G

1997-09-01

Extensive in vitro research on fibroblasts has defined numerous genetic and phenotypic changes associated with replicative senescence. Identification of T-cell replicative senescence as a feature of human immunodeficiency virus (HIV) disease and ageing suggests this phenomenon merits more careful consideration by immunologists, especially with regard to chronic infection, memory and adoptive immunotherapy.

Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.

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Dunn, Glynis; Klapsa, Dimitra; Wilton, Thomas; Stone, Lindsay; Minor, Philip D; Martin, Javier

2015-08-01

There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era.

PrimateLit Database

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Primate Info Net Related Databases NCRR PrimateLit: A bibliographic database for primatology Top of any problems with this service. We welcome your feedback. The PrimateLit database is no longer being Resources, National Institutes of Health. The database is a collaborative project of the Wisconsin Primate

Role of the DIS hairpin in replication of human immunodeficiency virus type 1

NARCIS (Netherlands)

Berkhout, B.; van Wamel, J. L.

1996-01-01

The virion-associated genome of human immunodeficiency virus type 1 consists of a noncovalently linked dimer of two identical, unspliced RNA molecules. A hairpin structure within the untranslated leader transcript is postulated to play a role in RNA dimerization through base pairing of the

Evaluation of a multiple-cycle, recombinant virus, growth competition assay that uses flow cytometry to measure replication efficiency of human immunodeficiency virus type 1 in cell culture.

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Dykes, Carrie; Wang, Jiong; Jin, Xia; Planelles, Vicente; An, Dong Sung; Tallo, Amanda; Huang, Yangxin; Wu, Hulin; Demeter, Lisa M

2006-06-01

Human immunodeficiency virus type 1 (HIV-1) replication efficiency or fitness, as measured in cell culture, has been postulated to correlate with clinical outcome of HIV infection, although this is still controversial. One limitation is the lack of high-throughput assays that can measure replication efficiency over multiple rounds of replication. We have developed a multiple-cycle growth competition assay to measure HIV-1 replication efficiency that uses flow cytometry to determine the relative proportions of test and reference viruses, each of which expresses a different reporter gene in place of nef. The reporter genes are expressed on the surface of infected cells and are detected by commercially available fluorescence-labeled antibodies. This method is less labor-intensive than those that require isolation and amplification of nucleic acids. The two reporter gene products are detected with similar specificity and sensitivity, and the proportion of infected cells in culture correlates with the amount of viral p24 antigen produced in the culture supernatant. HIV replication efficiencies of six different drug-resistant site-directed mutants were reproducibly quantified and were similar to those obtained with a growth competition assay in which the relative proportion of each variant was measured by sequence analysis, indicating that recombination between the pol and reporter genes was negligible. This assay also reproducibly quantified the relative fitness conferred by protease and reverse transcriptase sequences containing multiple drug resistance mutations, amplified from patient plasma. This flow cytometry-based growth competition assay offers advantages over current assays for HIV replication efficiency and should prove useful for the evaluation of patient samples in clinical trials.

Immunovirological analyses of chronically simian immunodeficiency virus SIVmnd-1- and SIVmnd-2-infected mandrills (Mandrillus sphinx).

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Apetrei, Cristian; Sumpter, Beth; Souquiere, Sandrine; Chahroudi, Ann; Makuwa, Maria; Reed, Patricia; Ribeiro, Ruy M; Pandrea, Ivona; Roques, Pierre; Silvestri, Guido

2011-12-01

Simian immunodeficiency virus (SIV) infection in African nonhuman primate (NHP) natural hosts is usually nonpathogenic, despite high levels of virus replication. We have previously shown that chronic SIV infection in sooty mangabeys (SMs) and African green monkeys (AGMs) is associated with low levels of immune activation and bystander T cell apoptosis. To compare these features with those observed in another natural host, the mandrill (MND), we conducted a cross-sectional survey of the 23 SIV-infected and 25 uninfected MNDs from the only semifree colony of mandrills available worldwide. Viral loads (VLs) were determined and phenotypic and functional analysis of peripheral blood- and lymph node-derived lymphocytes was performed. We found that mandrills chronically infected with SIVmnd-1 or SIVmnd-2 have similar levels of viral replication, and we observed a trend toward lower CD4+ T cell counts in chronically SIVmnd-2-infected MNDs than SIVmnd-1-infected MNDs. No correlation between CD4+ T cell counts and VLs in SIV-infected MNDs could be established. Of note, the levels of T cell activation, proliferation, and apoptosis were comparable between SIVmnd-1- and SIVmnd-2-infected MNDs and to those observed in uninfected animals, with the only exception being an increase in tumor necrosis factor alpha-producing CD8+ T cells in SIVmnd-2-infected MNDs. Overall, these findings recapitulate previous observations in SIV-infected SMs and AGMs and lend further evidence to the hypothesis that low levels of immune activation protect natural SIV hosts from disease progression.

Induction of Mucosal and Systemic Immunity to a Recombinant Simian Immunodeficiency Viral Protein

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Lehner, T.; Bergmeier, L. A.; Panagiotidi, C.; Tao, L.; Brookes, R.; Klavinskis, L. S.; Walker, P.; Walker, J.; Ward, R. G.; Hussain, L.; Gearing, A. J. H.; Adams, S. E.

1992-11-01

Heterosexual transmission through the cervico-vaginal mucosa is the principal route of human immunodeficiency virus (HIV) infection in Africa and is increasing in the United States and Europe. Vaginal immunization with simian immunodeficiency virus (SIV) had not yet been studied in nonhuman primates. Immune responses in macaques were investigated by stimulation of the genital and gut-associated lymphoid tissue with a recombinant, particulate SIV antigen. Vaginal, followed by oral, administration of the vaccine elicited three types of immunity: (i) gag protein p27-specific, secretory immunoglobulin A (IgA) and immunoglobulin G (IgG) in the vaginal fluid, (ii) specific CD4^+ T cell proliferation and helper function in B cell p27-specific IgA synthesis in the genital lymph nodes, and (iii) specific serum IgA and IgG, with CD4^+ T cell proliferative and helper functions in the circulating blood.

Suppression of feline immunodeficiency virus infection in vivo by 9-(2-phosphonomethoxyethyl)adenine

NARCIS (Netherlands)

Horzinek, M.C.; Egberink, H.F.; Borst, M.; Niphuis, H.; Balzarini, J.; Neu, H.; Schellekens, H.; Clercq, H. de; Koolen, M.J.M.

1990-01-01

The acyclic purine nucleoside analogue 9-(2-phosphonomethoxyethyl)adenine [PMEA; formerly referred to as 9-(2-phosphonylmethoxyethyl)adenine] is a potent and selective inhibitor of human immunodeficiency virus replication in vitro and of Moloney murine sarcoma virus-induced tumor formation in mice.

Understanding the Process of Envelope Glycoprotein Incorporation into Virions in Simian and Feline Immunodeficiency Viruses

Directory of Open Access Journals (Sweden)

José L. Affranchino

2014-01-01

Full Text Available The lentiviral envelope glycoproteins (Env mediate virus entry by interacting with specific receptors present at the cell surface, thereby determining viral tropism and pathogenesis. Therefore, Env incorporation into the virions formed by assembly of the viral Gag polyprotein at the plasma membrane of the infected cells is a key step in the replication cycle of lentiviruses. Besides being useful models of human immunodeficiency virus (HIV infections in humans and valuable tools for developing AIDS therapies and vaccines, simian and feline immunodeficiency viruses (SIV and FIV, respectively are relevant animal retroviruses; the study of which provides important information on how lentiviral replication strategies have evolved. In this review, we discuss the molecular mechanisms underlying the incorporation of the SIV and FIV Env glycoproteins into viral particles.

Impending extinction crisis of the world’s primates: Why primates matter

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Estrada, Alejandro; Garber, Paul A.; Rylands, Anthony B.; Roos, Christian; Fernandez-Duque, Eduardo; Di Fiore, Anthony; Nekaris, K. Anne-Isola; Nijman, Vincent; Heymann, Eckhard W.; Lambert, Joanna E.; Rovero, Francesco; Barelli, Claudia; Setchell, Joanna M.; Gillespie, Thomas R.; Mittermeier, Russell A.; Arregoitia, Luis Verde; de Guinea, Miguel; Gouveia, Sidney; Dobrovolski, Ricardo; Shanee, Sam; Shanee, Noga; Boyle, Sarah A.; Fuentes, Agustin; MacKinnon, Katherine C.; Amato, Katherine R.; Meyer, Andreas L. S.; Wich, Serge; Sussman, Robert W.; Pan, Ruliang; Kone, Inza; Li, Baoguo

2017-01-01

Nonhuman primates, our closest biological relatives, play important roles in the livelihoods, cultures, and religions of many societies and offer unique insights into human evolution, biology, behavior, and the threat of emerging diseases. They are an essential component of tropical biodiversity, contributing to forest regeneration and ecosystem health. Current information shows the existence of 504 species in 79 genera distributed in the Neotropics, mainland Africa, Madagascar, and Asia. Alarmingly, ~60% of primate species are now threatened with extinction and ~75% have declining populations. This situation is the result of escalating anthropogenic pressures on primates and their habitats—mainly global and local market demands, leading to extensive habitat loss through the expansion of industrial agriculture, large-scale cattle ranching, logging, oil and gas drilling, mining, dam building, and the construction of new road networks in primate range regions. Other important drivers are increased bushmeat hunting and the illegal trade of primates as pets and primate body parts, along with emerging threats, such as climate change and anthroponotic diseases. Often, these pressures act in synergy, exacerbating primate population declines. Given that primate range regions overlap extensively with a large, and rapidly growing, human population characterized by high levels of poverty, global attention is needed immediately to reverse the looming risk of primate extinctions and to attend to local human needs in sustainable ways. Raising global scientific and public awareness of the plight of the world’s primates and the costs of their loss to ecosystem health and human society is imperative. PMID:28116351

Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides.

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Jamie L Schafer

2015-09-01

Full Text Available Natural killer (NK cell responses in primates are regulated in part through interactions between two highly polymorphic molecules, the killer-cell immunoglobulin-like receptors (KIRs on NK cells and their major histocompatibility complex (MHC class I ligands on target cells. We previously reported that the binding of a common MHC class I molecule in the rhesus macaque, Mamu-A1*002, to the inhibitory receptor Mamu-KIR3DL05 is stabilized by certain simian immunodeficiency virus (SIV peptides, but not by others. Here we investigated the functional implications of these interactions by testing SIV peptides bound by Mamu-A1*002 for the ability to modulate Mamu-KIR3DL05+ NK cell responses. Twenty-eight of 75 SIV peptides bound by Mamu-A1*002 suppressed the cytolytic activity of primary Mamu-KIR3DL05+ NK cells, including three immunodominant CD8+ T cell epitopes previously shown to stabilize Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. Substitutions at C-terminal positions changed inhibitory peptides into disinhibitory peptides, and vice versa, without altering binding to Mamu-A1*002. The functional effects of these peptide variants on NK cell responses also corresponded to their effects on Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. In assays with mixtures of inhibitory and disinhibitory peptides, low concentrations of inhibitory peptides dominated to suppress NK cell responses. Consistent with the inhibition of Mamu-KIR3DL05+ NK cells by viral epitopes presented by Mamu-A1*002, SIV replication was significantly higher in Mamu-A1*002+ CD4+ lymphocytes co-cultured with Mamu-KIR3DL05+ NK cells than with Mamu-KIR3DL05- NK cells. These results demonstrate that viral peptides can differentially affect NK cell responses by modulating MHC class I interactions with inhibitory KIRs, and provide a mechanism by which immunodeficiency viruses may evade NK cell responses.

Olive baboons: a non-human primate model for testing dengue virus type 2 replication.

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Valdés, Iris; Gil, Lázaro; Castro, Jorge; Odoyo, Damián; Hitler, Rikoi; Munene, Elephas; Romero, Yaremis; Ochola, Lucy; Cosme, Karelia; Kariuki, Thomas; Guillén, Gerardo; Hermida, Lisset

2013-12-01

This study evaluated the use of a non-human primate, the olive baboon (Papio anubis), as a model of dengue infection. Olive baboons closely resemble humans genetically and physiologically and have been used extensively for assessing novel vaccine formulations. Two doses of dengue virus type 2 (DENV-2) were tested in baboons: 10(3) and 10(4) pfu. Similarly, African green monkeys received the same quantity of virus and acted as positive controls. Following exposure, high levels of viremia were detected in both animal species. There was a trend to detect more days of viremia and more homogeneous viral titers in animals receiving the low viral dose. In addition, baboons infected with the virus generally exhibited positive virus isolation 1 day later than African green monkeys. Humoral responses consisting of antiviral and neutralizing antibodies were detected in all animals after infection. We conclude that baboons provide an alternative non-human primate species for experimental DENV-2 infection and we recommend their use for further tests of vaccines, administering the lowest dose assayed: 10(3) pfu. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Vorinostat Renders the Replication-Competent Latent Reservoir of Human Immunodeficiency Virus (HIV Vulnerable to Clearance by CD8 T Cells

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Julia A. Sung

2017-09-01

Full Text Available Latently human immunodeficiency virus (HIV-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen production sufficient in quantity and duration to allow for recognition and clearance of persisting infection, we developed a latency clearance assay (LCA. The LCA is a quantitative viral outgrowth assay (QVOA that includes the addition of immune effectors capable of clearing cells expressing viral antigen. Here we show a reduction in the recovery of replication-competent virus from VOR exposed resting CD4 T cells following addition of immune effectors for a discrete period. Take home message: VOR exposure leads to sufficient production of viral protein on the cell surface, creating a window of vulnerability within this latent reservoir in antiretroviral therapy (ART-suppressed HIV-infected individuals that allows the clearance of latently infected cells by an array of effector mechanisms.

Moderate restriction of macrophage-tropic human immunodeficiency virus type 1 by SAMHD1 in monocyte-derived macrophages.

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Taya, Kahoru; Nakayama, Emi E; Shioda, Tatsuo

2014-01-01

Macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains are able to grow to high titers in human monocyte-derived macrophages. However, it was recently reported that cellular protein SAMHD1 restricts HIV-1 replication in human cells of the myeloid lineage, including monocyte-derived macrophages. Here we show that degradation of SAMHD1 in monocyte-derived macrophages was associated with moderately enhanced growth of the macrophage-tropic HIV-1 strain. SAMHD1 degradation was induced by treating target macrophages with vesicular stomatitis virus glycoprotein-pseudotyped human immunodeficiency virus type 2 (HIV-2) particles containing viral protein X. For undifferentiated monocytes, HIV-2 particle treatment allowed undifferentiated monocytes to be fully permissive for productive infection by the macrophage-tropic HIV-1 strain. In contrast, untreated monocytes were totally resistant to HIV-1 replication. These results indicated that SAMHD1 moderately restricts even a macrophage-tropic HIV-1 strain in monocyte-derived macrophages, whereas the protein potently restricts HIV-1 replication in undifferentiated monocytes.

Efficacy of Antiviral Drugs against Feline Immunodeficiency Virus

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Katrin Hartmann

2015-12-01

Full Text Available Feline immunodeficiency virus (FIV is one of the most common infectious agents affecting cats worldwide .FIV and human immunodeficiency virus (HIV share many properties: both are lifelong persistent lentiviruses that are similar genetically and morphologically and both viruses propagate in T-lymphocytes, macrophages, and neural cells. Experimentally infected cats have measurable immune suppression, which sometimes progresses to an acquired immunodeficiency syndrome. A transient initial state of infection is followed by a long latent stage with low virus replication and absence of clinical signs. In the terminal stage, both viruses can cause severe immunosuppression. Thus, FIV infection in cats has become an important natural model for studying HIV infection in humans, especially for evaluation of antiviral compounds. Of particular importance for chemotherapeutic studies is the close similarity between the reverse transcriptase (RT of FIV and HIV, which results in high in vitro susceptibility of FIV to many RT-targeted antiviral compounds used in the treatment of HIV-infected patients. Thus, the aim of this article is to provide an up-to-date review of studies on antiviral treatment of FIV, focusing on commercially available compounds for human or animal use.

Strain-specific viral distribution and neuropathology of feline immunodeficiency virus.

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Miller, Craig; Bielefeldt-Ohmann, Helle; MacMillan, Martha; Huitron-Resendiz, Salvador; Henriksen, Steven; Elder, John; VandeWoude, Susan

2011-10-15

Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats, and is the causative agent of feline AIDS. Similar to human immunodeficiency virus (HIV), the pathogenesis of FIV involves infection of lymphocytes and macrophages, and results in chronic progressive immune system collapse and death. Neuropathologic correlates of FIV infection have not yet been elucidated, and may be relevant to understanding HIV-associated neurologic disease (neuroAIDS). As in HIV, FIV strains have been shown to express differential tendencies towards development of clinical neuroAIDS. To interrogate viral genetic determinants that might contribute to neuropathogenicity, cats were exposed to two well-characterized FIV strains with divergent clinical phenotypes and a chimeric strain as follows: FIV(PPR) (PPR, relatively apathogenic but associated with neurologic manifestations), FIV(C36) (C36, immunopathogenic but without associated neurologic disease), and Pcenv (a chimeric virus consisting of a PPR backbone with substituted C36 env region). A sham inoculum control group was also included. Peripheral nerve conduction velocity, CNS imaging studies, viral loads and hematologic analysis were performed over a 12 month period. At termination of the study (350 days post-inoculation), brain sections were obtained from four anatomic locations known to be involved in human and primate lentiviral neuroAIDS. Histological and immunohistochemical evaluation with seven markers of inflammation revealed that Pcenv infection resulted in mild inflammation of the CNS, microglial activation, neuronal degeneration and apoptosis, while C36 and PPR strains induced minimal neuropathologic changes. Conduction velocity aberrations were noted peripherally in all three groups at 63 weeks post-infection. Pcenv viral load in this study was intermediate to the parental strains (C36 demonstrating the highest viral load and PPR the lowest). These results collectively suggest that (i) 3' C36

Estrogen regulation of microcephaly genes and evolution of brain sexual dimorphism in primates.

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Shi, Lei; Lin, Qiang; Su, Bing

2015-06-30

Sexual dimorphism in brain size is common among primates, including humans, apes and some Old World monkeys. In these species, the brain size of males is generally larger than that of females. Curiously, this dimorphism has persisted over the course of primate evolution and human origin, but there is no explanation for the underlying genetic controls that have maintained this disparity in brain size. In the present study, we tested the effect of the female hormone (estradiol) on seven genes known to be related to brain size in both humans and nonhuman primates, and we identified half estrogen responsive elements (half EREs) in the promoter regions of four genes (MCPH1, ASPM, CDK5RAP2 and WDR62). Likewise, at sequence level, it appears that these half EREs are generally conserved across primates. Later testing via a reporter gene assay and cell-based endogenous expression measurement revealed that estradiol could significantly suppress the expression of the four affected genes involved in brain size. More intriguingly, when the half EREs were deleted from the promoters, the suppression effect disappeared, suggesting that the half EREs mediate the regulation of estradiol on the brain size genes. We next replicated these experiments using promoter sequences from chimpanzees and rhesus macaques, and observed a similar suppressive effect of estradiol on gene expression, suggesting that this mechanism is conserved among primate species that exhibit brain size dimorphism. Brain size dimorphism among certain primates, including humans, is likely regulated by estrogen through its sex-dependent suppression of brain size genes during development.

Molecular investigation of the evolutionary history and diversity of primate T-lymphotropic virus types 1 and 3

NARCIS (Netherlands)

Van Dooren, Sonia Jeanne Albertine

2005-01-01

The Primate T-lymphotropic viruses (PTLV) comprise a group of complex retroviruses that infect both humans (HTLV) and simians (STLV) and have been associated with leukaemia or lymphoma and with neurological disorders. PTLVs have a peculiar replication strategy: their way of life is mainly determined

Feline immunodeficiency virus envelope glycoproteins antagonize tetherin through a distinctive mechanism that requires virion incorporation.

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Morrison, James H; Guevara, Rebekah B; Marcano, Adriana C; Saenz, Dyana T; Fadel, Hind J; Rogstad, Daniel K; Poeschla, Eric M

2014-03-01

BST2/tetherin inhibits the release of enveloped viruses from cells. Primate lentiviruses have evolved specific antagonists (Vpu, Nef, and Env). Here we characterized tetherin proteins of species representing both branches of the order Carnivora. Comparison of tiger and cat (Feliformia) to dog and ferret (Caniformia) genes demonstrated that the tiger and cat share a start codon mutation that truncated most of the tetherin cytoplasmic tail early in the Feliformia lineage (19 of 27 amino acids, including the dual tyrosine motif). Alpha interferon (IFN-α) induced tetherin and blocked feline immunodeficiency virus (FIV) replication in lymphoid and nonlymphoid feline cells. Budding of bald FIV and HIV particles was blocked by carnivore tetherins. However, infectious FIV particles were resistant, and spreading FIV replication was uninhibited. Antagonism mapped to the envelope glycoprotein (Env), which rescued FIV from carnivore tetherin restriction when expressed in trans but, in contrast to known antagonists, did not rescue noncognate particles. Also unlike the primate lentiviral antagonists, but similar to the Ebola virus glycoprotein, FIV Env did not reduce intracellular or cell surface tetherin levels. Furthermore, FIV-enveloped FIV particles actually required tetherin for optimal release from cells. The results show that FIV Envs mediate a distinctive tetherin evasion. Well adapted to a phylogenetically ancient tetherin tail truncation in the Felidae, it requires functional virion incorporation of Env, and it shields the budding particle without downregulating plasma membrane tetherin. Moreover, FIV has evolved dependence on this protein: particles containing FIV Env need tetherin for optimal release from the cell, while Env(-) particles do not. HIV-1 antagonizes the restriction factor tetherin with the accessory protein Vpu, while HIV-2 and the filovirus Ebola use their envelope (Env) glycoproteins for this purpose. It turns out that the FIV tetherin antagonist is

Stability of the gorilla microbiome despite simian immunodeficiency virus infection.

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Moeller, Andrew H; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H; Ochman, Howard

2015-02-01

Simian immunodeficiency viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in faecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we examine the effects of SIVgor, a close relative of SIVcpz of chimpanzees and HIV-1 of humans, on the gut bacterial communities residing within wild gorillas, revealing that gorilla gut microbiomes are exceptionally robust to SIV infection. In contrast to the microbiomes of HIV-1-infected humans and SIVcpz-infected chimpanzees, SIVgor-infected gorilla microbiomes exhibit neither rises in the frequencies of opportunistic pathogens nor elevated rates of microbial turnover within individual hosts. Regardless of SIV infection status, gorilla microbiomes assort into enterotypes, one of which is compositionally analogous to those identified in humans and chimpanzees. The other gorilla enterotype appears specialized for a leaf-based diet and is enriched in environmentally derived bacterial genera. We hypothesize that the acquisition of this gorilla-specific enterotype was enabled by lowered immune system control over the composition of the microbiome. Our results indicate differences between the pathology of SIVgor and SIVcpz/HIV-1 infections, demonstrating the utility of investigating host microbial ecology as a means for studying disease in wild primates of high conservation priority. © 2014 John Wiley & Sons Ltd.

Nutritional contributions of insects to primate diets: implications for primate evolution.

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Rothman, Jessica M; Raubenheimer, David; Bryer, Margaret A H; Takahashi, Maressa; Gilbert, Christopher C

2014-06-01

Insects and other invertebrates form a portion of many living and extinct primate diets. We review the nutritional profiles of insects in comparison with other dietary items, and discuss insect nutrients in relation to the nutritional needs of living primates. We find that insects are incorporated into some primate diets as staple foods whereby they are the majority of food intake. They can also be incorporated as complements to other foods in the diet, providing protein in a diet otherwise dominated by gums and/or fruits, or be incorporated as supplements to likely provide an essential nutrient that is not available in the typical diet. During times when they are very abundant, such as in insect outbreaks, insects can serve as replacements to the usual foods eaten by primates. Nutritionally, insects are high in protein and fat compared with typical dietary items like fruit and vegetation. However, insects are small in size and for larger primates (>1 kg) it is usually nutritionally profitable only to consume insects when they are available in large quantities. In small quantities, they may serve to provide important vitamins and fatty acids typically unavailable in primate diets. In a brief analysis, we found that soft-bodied insects are higher in fat though similar in chitin and protein than hard-bodied insects. In the fossil record, primates can be defined as soft- or hard-bodied insect feeders based on dental morphology. The differences in the nutritional composition of insects may have implications for understanding early primate evolution and ecology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Modification of a loop sequence between α-helices 6 and 7 of virus capsid (CA protein in a human immunodeficiency virus type 1 (HIV-1 derivative that has simian immunodeficiency virus (SIVmac239 vif and CA α-helices 4 and 5 loop improves replication in cynomolgus monkey cells

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Adachi Akio

2009-08-01

Full Text Available Abstract Background Human immunodeficiency virus type 1 (HIV-1 productively infects only humans and chimpanzees but not cynomolgus or rhesus monkeys while simian immunodeficiency virus isolated from macaque (SIVmac readily establishes infection in those monkeys. Several HIV-1 and SIVmac chimeric viruses have been constructed in order to develop an animal model for HIV-1 infection. Construction of an HIV-1 derivative which contains sequences of a SIVmac239 loop between α-helices 4 and 5 (L4/5 of capsid protein (CA and the entire SIVmac239 vif gene was previously reported. Although this chimeric virus could grow in cynomolgus monkey cells, it did so much more slowly than did SIVmac. It was also reported that intrinsic TRIM5α restricts the post-entry step of HIV-1 replication in rhesus and cynomolgus monkey cells, and we previously demonstrated that a single amino acid in a loop between α-helices 6 and 7 (L6/7 of HIV type 2 (HIV-2 CA determines the susceptibility of HIV-2 to cynomolgus monkey TRIM5α. Results In the study presented here, we replaced L6/7 of HIV-1 CA in addition to L4/5 and vif with the corresponding segments of SIVmac. The resultant HIV-1 derivatives showed enhanced replication capability in established T cell lines as well as in CD8+ cell-depleted primary peripheral blood mononuclear cells from cynomolgus monkey. Compared with the wild type HIV-1 particles, the viral particles produced from a chimeric HIV-1 genome with those two SIVmac loops were less able to saturate the intrinsic restriction in rhesus monkey cells. Conclusion We have succeeded in making the replication of simian-tropic HIV-1 in cynomolgus monkey cells more efficient by introducing into HIV-1 the L6/7 CA loop from SIVmac. It would be of interest to determine whether HIV-1 derivatives with SIVmac CA L4/5 and L6/7 can establish infection of cynomolgus monkeys in vivo.

Effects of the deletion of early region 4 (E4 open reading frame 1 (orf1, orf1-2, orf1-3 and orf1-4 on virus-host cell interaction, transgene expression, and immunogenicity of replicating adenovirus HIV vaccine vectors.

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Michael A Thomas

Full Text Available The global health burden engendered by human immunodeficiency virus (HIV-induced acquired immunodeficiency syndrome (AIDS is a sobering reminder of the pressing need for a preventative vaccine. In non-human primate models replicating adenovirus (Ad-HIV/SIV recombinant vaccine vectors have been shown to stimulate potent immune responses culminating in protection against challenge exposures. Nonetheless, an increase in the transgene carrying capacity of these Ad vectors, currently limited to approximately 3000 base pairs, would greatly enhance their utility. Using a replicating, E3-deleted Ad type 5 host range mutant (Ad5 hr encoding full-length single-chain HIVBaLgp120 linked to the D1 and D2 domains of rhesus macaque CD4 (rhFLSC we systematically deleted the genes encoding early region 4 open reading frame 1 (E4orf1 through E4orf4. All the Ad-rhFLSC vectors produced similar levels of viral progeny. Cell cycle analysis of infected human and monkey cells revealed no differences in virus-host interaction. The parental and E4-deleted viruses expressed comparable levels of the transgene with kinetics similar to Ad late proteins. Similar levels of cellular immune responses and transgene-specific antibodies were elicited in vaccinated mice. However, differences in recognition of Ad proteins and induced antibody subtypes were observed, suggesting that the E4 gene products might modulate antibody responses by as yet unknown mechanisms. In short, we have improved the transgene carrying capacity by one thousand base pairs while preserving the replicability, levels of transgene expression, and immunogenicity critical to these vaccine vectors. This additional space allows for flexibility in vaccine design that could not be obtained with the current vector and as such should facilitate the goal of improving vaccine efficacy. To the best of our knowledge, this is the first report describing the effects of these E4 deletions on transgene expression and

Effects of the deletion of early region 4 (E4) open reading frame 1 (orf1), orf1-2, orf1-3 and orf1-4 on virus-host cell interaction, transgene expression, and immunogenicity of replicating adenovirus HIV vaccine vectors.

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Thomas, Michael A; Song, Rui; Demberg, Thorsten; Vargas-Inchaustegui, Diego A; Venzon, David; Robert-Guroff, Marjorie

2013-01-01

The global health burden engendered by human immunodeficiency virus (HIV)-induced acquired immunodeficiency syndrome (AIDS) is a sobering reminder of the pressing need for a preventative vaccine. In non-human primate models replicating adenovirus (Ad)-HIV/SIV recombinant vaccine vectors have been shown to stimulate potent immune responses culminating in protection against challenge exposures. Nonetheless, an increase in the transgene carrying capacity of these Ad vectors, currently limited to approximately 3000 base pairs, would greatly enhance their utility. Using a replicating, E3-deleted Ad type 5 host range mutant (Ad5 hr) encoding full-length single-chain HIVBaLgp120 linked to the D1 and D2 domains of rhesus macaque CD4 (rhFLSC) we systematically deleted the genes encoding early region 4 open reading frame 1 (E4orf1) through E4orf4. All the Ad-rhFLSC vectors produced similar levels of viral progeny. Cell cycle analysis of infected human and monkey cells revealed no differences in virus-host interaction. The parental and E4-deleted viruses expressed comparable levels of the transgene with kinetics similar to Ad late proteins. Similar levels of cellular immune responses and transgene-specific antibodies were elicited in vaccinated mice. However, differences in recognition of Ad proteins and induced antibody subtypes were observed, suggesting that the E4 gene products might modulate antibody responses by as yet unknown mechanisms. In short, we have improved the transgene carrying capacity by one thousand base pairs while preserving the replicability, levels of transgene expression, and immunogenicity critical to these vaccine vectors. This additional space allows for flexibility in vaccine design that could not be obtained with the current vector and as such should facilitate the goal of improving vaccine efficacy. To the best of our knowledge, this is the first report describing the effects of these E4 deletions on transgene expression and immunogenicity in a

Comparative evaluation of oral and intranasal priming with replication-competent adenovirus 5 host range mutant (Ad5hr)-simian immunodeficiency virus (SIV) recombinant vaccines on immunogenicity and protective efficacy against SIV(mac251).

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Zhou, Qifeng; Hidajat, Rachmat; Peng, Bo; Venzon, David; Aldrich, M Kristine; Richardson, Ersell; Lee, Eun Mi; Kalyanaraman, V S; Grimes, George; Gómez-Román, V Raúl; Summers, L Ebonita; Malkevich, Nina; Robert-Guroff, Marjorie

2007-11-19

Oral, replication-competent Ad-HIV vaccines are advancing to human trials. Previous evaluation of protective efficacy in non-human primates has primarily followed upper respiratory tract administrations. Here we compared sequential oral (O/O) versus intranasal/oral (I/O) priming of rhesus macaques with Ad5 host range mutant-SIV recombinants expressing SIV env/rev, gag, and nef genes followed by boosting with SIV gp120 protein. Cellular immune responses in PBMC were stronger and more frequent after I/O administration. Both groups developed mucosal immunity, including memory cells in bronchial alveolar lavage, and gut-homing receptors on PBMC. Following intrarectal SIV(mac251) challenge, both groups exhibited equivalent, significant protection and robust post-challenge cellular immunity. Our results illustrate the promise of oral replication-competent Ad-recombinant vaccines. Pre-challenge PBMC ELISPOT and proliferative responses did not predict protection in the O/O group, highlighting the need for simple, non-invasive methods to reliably assess mucosal immunity.

No need to replace an "anomalous" primate (Primates) with an "anomalous" bear (Carnivora, Ursidae).

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Gutiérrez, Eliécer E; Pine, Ronald H

2015-01-01

By means of mitochondrial 12S rRNA sequencing of putative "yeti", "bigfoot", and other "anomalous primate" hair samples, a recent study concluded that two samples, presented as from the Himalayas, do not belong to an "anomalous primate", but to an unknown, anomalous type of ursid. That is, that they match 12S rRNA sequences of a fossil Polar Bear (Ursusmaritimus), but neither of modern Polar Bears, nor of Brown Bears (Ursusarctos), the closest relative of Polar Bears, and one that occurs today in the Himalayas. We have undertaken direct comparison of sequences; replication of the original comparative study; inference of phylogenetic relationships of the two samples with respect to those from all extant species of Ursidae (except for the Giant Panda, Ailuropodamelanoleuca) and two extinct Pleistocene species; and application of a non-tree-based population aggregation approach for species diagnosis and identification. Our results demonstrate that the very short fragment of the 12S rRNA gene sequenced by Sykes et al. is not sufficiently informative to support the hypotheses provided by these authors with respect to the taxonomic identity of the individuals from which these sequences were obtained. We have concluded that there is no reason to believe that the two samples came from anything other than Brown Bears. These analyses afforded an opportunity to test the monophyly of morphologically defined species and to comment on both their phylogenetic relationships and future efforts necessary to advance our understanding of ursid systematics.

Fangchinoline inhibits human immunodeficiency virus type 1 replication by interfering with gp160 proteolytic processing.

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Zhitao Wan

Full Text Available The introduction of highly active antiretroviral therapy has led to a significant reduction in the morbidity and mortality of acquired immunodeficiency syndrome patients. However, the emergence of drug resistance has resulted in the failure of treatments in large numbers of patients and thus necessitates the development of new classes of anti-HIV drugs. In this study, more than 200 plant-derived small-molecule compounds were evaluated in a cell-based HIV-1 antiviral screen, resulting in the identification of a novel HIV-1 inhibitor (fangchinoline. Fangchinoline, a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae, exhibited antiviral activity against HIV-1 laboratory strains NL4-3, LAI and BaL in MT-4 and PM1 cells with a 50% effective concentration ranging from 0.8 to 1.7 µM. Mechanism-of-action studies showed that fangchinoline did not exhibit measurable antiviral activity in TZM-b1 cells but did inhibit the production of infectious virions in HIV-1 cDNA transfected 293T cells, which suggests that the compound targets a late event in infection cycle. Furthermore, the antiviral effect of fangchinoline seems to be HIV-1 envelope-dependent, as the production of infectious HIV-1 particles packaged with a heterologous envelope, the vesicular stomatitis virus G glycoprotein, was unaffected by fangchinoline. Western blot analysis of HIV envelope proteins expressed in transfected 293T cells and in isolated virions showed that fangchinoline inhibited HIV-1 gp160 processing, resulting in reduced envelope glycoprotein incorporation into nascent virions. Collectively, our results demonstrate that fangchinoline inhibits HIV-1 replication by interfering with gp160 proteolytic processing. Fangchinoline may serve as a starting point for developing a new HIV-1 therapeutic approach.

Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

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Kim, Jiae; Peachman, Kristina K.; Jobe, Ousman; Morrison, Elaine B.; Allam, Atef; Jagodzinski, Linda; Casares, Sofia A.; Rao, Mangala

2017-01-01

Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP) models for studying human immunodeficiency virus (HIV)-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several different types of humanized mice have been developed with varying levels of reconstitution of human CD45+ cells. In this study, we utilized humanized Rag1KO.IL2RγcKO.NOD mice expressing HLA class II (DR4) molecule (DRAG mice) infused with HLA-matched hematopoietic stem cells from umbilical cord blood to study early events after HIV-1 infection, since the mucosal tissues of these mice are highly enriched for human lymphocytes and express the receptors and coreceptors needed for HIV-1 entry. We examined the various tissues on days 4, 7, 14, and 21 after an intravaginal administration of a single dose of purified primary HIV-1. Plasma HIV-1 RNA was detected as early as day 7, with 100% of the animals becoming plasma RNA positive by day 21 post-infection. Single cells were isolated from lymph nodes, bone marrow, spleen, gut, female reproductive tissue, and brain and analyzed for gag RNA and strong stop DNA by quantitative (RT)-PCR. Our data demonstrated the presence of HIV-1 viral RNA and DNA in all of the tissues examined and that the virus was replication competent and spread rapidly. Bone marrow, gut, and lymph nodes were viral RNA positive by day 4 post-infection, while other tissues and plasma became positive typically between 7 and 14 days post-infection. Interestingly, the brain was the last tissue to become HIV-1 viral RNA and DNA positive by day 21 post-infection. These data support the notion that humanized DRAG mice could serve as an excellent model for studying the

Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

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Jiae Kim

2017-10-01

Full Text Available Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP models for studying human immunodeficiency virus (HIV-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several different types of humanized mice have been developed with varying levels of reconstitution of human CD45+ cells. In this study, we utilized humanized Rag1KO.IL2RγcKO.NOD mice expressing HLA class II (DR4 molecule (DRAG mice infused with HLA-matched hematopoietic stem cells from umbilical cord blood to study early events after HIV-1 infection, since the mucosal tissues of these mice are highly enriched for human lymphocytes and express the receptors and coreceptors needed for HIV-1 entry. We examined the various tissues on days 4, 7, 14, and 21 after an intravaginal administration of a single dose of purified primary HIV-1. Plasma HIV-1 RNA was detected as early as day 7, with 100% of the animals becoming plasma RNA positive by day 21 post-infection. Single cells were isolated from lymph nodes, bone marrow, spleen, gut, female reproductive tissue, and brain and analyzed for gag RNA and strong stop DNA by quantitative (RT-PCR. Our data demonstrated the presence of HIV-1 viral RNA and DNA in all of the tissues examined and that the virus was replication competent and spread rapidly. Bone marrow, gut, and lymph nodes were viral RNA positive by day 4 post-infection, while other tissues and plasma became positive typically between 7 and 14 days post-infection. Interestingly, the brain was the last tissue to become HIV-1 viral RNA and DNA positive by day 21 post-infection. These data support the notion that humanized DRAG mice could serve as an excellent model

Ex-vivo expansion of nonhuman primate CD34+ cells by stem cell factor Sall4B

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Bin Shen

2016-10-01

Full Text Available Abstract Background Hematopoietic CD34+ stem cells are widely used in the clinical therapy of complicated blood diseases. Stem cell factor Sall4B is a zinc finger transcription factor that plays a vital role in hematopoietic stem cell expansion. The purpose of our current study is to further evaluate how Sall4B might affect the expansion of CD34+ cells derived from nonhuman primates. Methods Sall4B was overexpressed in nonhuman primate bone marrow-derived CD34+ cells via a lentiviral transduction system. The granulocyte–erythrocyte–macrophage–megakaryocyte colony-forming unit (CFU assay evaluated the differentiation potential of primate CD34+ cells that were expanded with Sall4B. Furthermore, an in-vivo murine system was employed to evaluate the hematopoietic potential of primate Sall4B-expanded CD34+ cells. Results Overexpression of Sall4B promoted ex-vivo nonhuman primate CD34+ cell expansion by 9.21 ± 1.94-fold on day 9, whereas lentiviral transduction without Sall4B expanded cells by only 2.95 ± 0.77-fold. Sall4B maintained a significant percentage of CD34+ cells as well. The CFU assay showed that the Sall4B-expanded CD34+ cells still possessed multilineage differentiation potential. A study using nonobese diabetic/severe combined immunodeficiency (NOD/SCID mice in vivo revealed that Sall4B led to an increase in the number of repopulating cells and the 9-day-old Sall4B-transduced CD34+ cells still possess self-renewal and multilineage differentiation capacity in vivo, which are similar stemness characteristics to those in freshly isolated primate bone marrow-derived CD34+ cells. Conclusions We investigated the expansion of nonhuman primate bone marrow-derived CD34+ cells using the Sall4B lentiviral overexpression approach; our findings provide a new perspective on mechanisms of rapid stem cell proliferation. The utilization of Sall4B to expand CD34+ cells on a large scale through use of suitable model systems would prove

Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization.

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Maxfield, Lori F; Abbink, Peter; Stephenson, Kathryn E; Borducchi, Erica N; Ng'ang'a, David; Kirilova, Marinela M; Paulino, Noelix; Boyd, Michael; Shabram, Paul; Ruan, Qian; Patel, Mayank; Barouch, Dan H

2015-11-01

Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors. Copyright © 2015, Maxfield et al.

Feline Immunodeficiency Virus Cross-Species Transmission: Implications for Emergence of New Lentiviral Infections.

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Lee, Justin; Malmberg, Jennifer L; Wood, Britta A; Hladky, Sahaja; Troyer, Ryan; Roelke, Melody; Cunningham, Mark; McBride, Roy; Vickers, Winston; Boyce, Walter; Boydston, Erin; Serieys, Laurel; Riley, Seth; Crooks, Kevin; VandeWoude, Sue

2017-03-01

Owing to a complex history of host-parasite coevolution, lentiviruses exhibit a high degree of species specificity. Given the well-documented viral archeology of human immunodeficiency virus (HIV) emergence following human exposures to simian immunodeficiency virus (SIV), an understanding of processes that promote successful cross-species lentiviral transmissions is highly relevant. We previously reported natural cross-species transmission of a subtype of feline immunodeficiency virus, puma lentivirus A (PLVA), between bobcats ( Lynx rufus ) and mountain lions ( Puma concolor ) for a small number of animals in California and Florida. In this study, we investigate host-specific selection pressures, within-host viral fitness, and inter- versus intraspecies transmission patterns among a larger collection of PLV isolates from free-ranging bobcats and mountain lions. Analyses of proviral and viral RNA levels demonstrate that PLVA fitness is severely restricted in mountain lions compared to that in bobcats. We document evidence of diversifying selection in three of six PLVA genomes from mountain lions, but we did not detect selection among 20 PLVA isolates from bobcats. These findings support the hypothesis that PLVA is a bobcat-adapted virus which is less fit in mountain lions and under intense selection pressure in the novel host. Ancestral reconstruction of transmission events reveals that intraspecific PLVA transmission has occurred among panthers ( Puma concolor coryi ) in Florida following the initial cross-species infection from bobcats. In contrast, interspecific transmission from bobcats to mountain lions predominates in California. These findings document outcomes of cross-species lentiviral transmission events among felids that compare to the emergence of HIV from nonhuman primates. IMPORTANCE Cross-species transmission episodes can be singular, dead-end events or can result in viral replication and spread in the new species. The factors that determine which

Electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins

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Katarzyna eBozek

2012-06-01

Full Text Available Human immunodeficiency virus type 2 (HIV-2 and simian immunodeficiency virus isolated from a macaque monkey (SIVmac are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm. Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5α, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh monkey TRIM5α, while that of SIVmac strain 239 (SIVmac239 is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5α, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5α-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5. As L4/5 is one of the major determinants of Rh TRIM5α sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5α may show complementarity to the HIV-2 GH123 capsid surface charge distribution.

Transmission of MDR MRSA between primates, their environment and personnel at a United States primate centre.

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Soge, Olusegun O; No, David; Michael, Karen E; Dankoff, Jennifer; Lane, Jennifer; Vogel, Keith; Smedley, Jeremy; Roberts, Marilyn C

2016-10-01

MDR MRSA isolates cultured from primates, their facility and primate personnel from the Washington National Primate Research Center were characterized to determine whether they were epidemiologically related to each other and if they represented common local human-associated MRSA strains. Human and primate nasal and composite environmental samples were collected, enriched and selected on medium supplemented with oxacillin and polymyxin B. Isolates were biochemically verified as Staphylococcus aureus and screened for the mecA gene. Selected isolates were characterized using SCCmec typing, MLST and WGS. Nasal cultures were performed on 596 primates and 105 (17.6%) were MRSA positive. Two of 79 (2.5%) personnel and two of 56 (3.6%) composite primate environmental facility samples were MRSA positive. Three MRSA isolates from primates, one MRSA from personnel, two environmental MRSA and one primate MSSA were ST188 and were the same strain type by conventional typing methods. ST188 isolates were related to a 2007 ST188 human isolate from Hong Kong. Both MRSA isolates from out-of-state primates had a novel MLST type, ST3268, and an unrelated group. All isolates carried ≥1 other antibiotic resistance gene(s), including tet(38), the only tet gene identified. ST188 is very rare in North America and has almost exclusively been identified in people from Pan-Asia, while ST3268 is a newly reported MRSA type. The data suggest that the primate MDR MRSA was unlikely to come from primate centre employees. Captive primates are likely to be an unappreciated source of MRSA. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Variability of bio-clinical parameters in Chinese-origin Rhesus macaques infected with simian immunodeficiency virus: a nonhuman primate AIDS model.

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Song Chen

Full Text Available BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs infected with simian immunodeficiency virus (SIV have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL FINDINGS: By randomizing 150 (78 male and 72 female Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group challenged with intrarectal (i.r. SIVmac239, intravenous (i.v. SIVmac239, or i.v. SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1-2 weeks. Plasma viral load (VL peaked at weeks 1-2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68. The rates of progression to AIDS or death were more rapid in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with i.r. or i.v. SIVmac239. The variability (standard deviation in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (i.r. or i.v. than in those infected with SIVmac251 (i.v., allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies.

Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates.

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Saunders, Kevin O; Santra, Sampa; Parks, Robert; Yates, Nicole L; Sutherland, Laura L; Scearce, Richard M; Balachandran, Harikrishnan; Bradley, Todd; Goodman, Derrick; Eaton, Amanda; Stanfield-Oakley, Sherry A; Tartaglia, James; Phogat, Sanjay; Pantaleo, Giuseppe; Esteban, Mariano; Gomez, Carmen E; Perdiguero, Beatriz; Jacobs, Bertram; Kibler, Karen; Korber, Bette; Montefiori, David C; Ferrari, Guido; Vandergrift, Nathan; Liao, Hua-Xin; Tomaras, Georgia D; Haynes, Barton F

2018-04-15

A preventive human immunodeficiency virus type 1 (HIV-1) vaccine is an essential part of the strategy to eradicate AIDS. A critical question is whether antibodies that do not neutralize primary isolate (tier 2) HIV-1 strains can protect from infection. In this study, we investigated the ability of an attenuated poxvirus vector (NYVAC) prime-envelope gp120 boost to elicit potentially protective antibody responses in a rhesus macaque model of mucosal simian-human immunodeficiency virus (SHIV) infection. NYVAC vector delivery of a group M consensus envelope, trivalent mosaic envelopes, or a natural clade B isolate B.1059 envelope elicited antibodies that mediated neutralization of tier 1 viruses, cellular cytotoxicity, and phagocytosis. None of the macaques made neutralizing antibodies against the tier 2 SHIV SF162P3 used for mucosal challenge. Significant protection from infection was not observed for the three groups of vaccinated macaques compared to unvaccinated macaques, although binding antibody to HIV-1 Env correlated with decreased viremia after challenge. Thus, NYVAC Env prime-gp120 boost vaccination elicited polyfunctional, nonneutralizing antibody responses with minimal protective activity against tier 2 SHIV mucosal challenge. IMPORTANCE The antibody responses that confer protection against HIV-1 infection remain unknown. Polyfunctional antibody responses correlated with time to infection in previous macaque studies. Determining the ability of vaccines to induce these types of responses is critical for understanding how to improve upon the one efficacious human HIV-1 vaccine trial completed thus far. We characterized the antibody responses induced by a NYVAC-protein vaccine and determined the protective capacity of polyfunctional antibody responses in an R5, tier 2 mucosal SHIV infection model. Copyright © 2018 American Society for Microbiology.

Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the G protein of vesicular stomatitis virus

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Kuate, Seraphin; Stahl-Hennig, Christiane; Stoiber, Heribert; Nchinda, Godwin; Floto, Anja; Franz, Monika; Sauermann, Ulrike; Bredl, Simon; Deml, Ludwig; Ignatius, Ralf; Norley, Steve; Racz, Paul; Tenner-Racz, Klara; Steinman, Ralph M.; Wagner, Ralf; Uberla, Klaus

2006-01-01

Vaccination with exogenous antigens such as recombinant viral proteins, immunodeficiency virus-derived whole inactivated virus particles, or virus-like particles (VLP) has generally failed to provide sufficient protection in animal models for AIDS. Pseudotyping VLPs with the vesicular stomatitis virus G protein (VSV-G), which is known to mediate entry into dendritic cells, might allow more efficient stimulation of immune responses. Therefore, we pseudotyped noninfectious immunodeficiency virus-like particles with VSV-G and carried out a preliminary screen of their immunogenicity and vaccination efficacy. Incorporation of VSV-G into HIV-1 VLPs led to hundred-fold higher antibody titers to HIV-1 Gag and enhancement of T cell responses in mice. Repeated vaccination of rhesus monkeys for 65 weeks with VSV-G pseudotyped simian immunodeficiency virus (SIV)-like particles (VLP[G]) provided initial evidence for efficient suppression of viral load after mucosal challenge with the SIVmac239 virus. Challenge of monkeys after a 28 week vaccination regimen with VLP[G] led to a reduction in peak viremia, but persistent suppression of viral load was not achieved. Due to limitations in the number of animals available for this study, improved efficacy of VSV-G pseudotyped VLPs in nonhuman primates could not be demonstrated. However, mouse experiments revealed that pseudotyping of VLPs with fusion-competent VSV-G clearly improves their immunogenicity. Additional strategies, particularly adjuvants, should be considered to provide greater protection against a challenge with pathogenic immunodeficiency virus

A molecular phylogeny of living primates.

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Perelman, Polina; Johnson, Warren E; Roos, Christian; Seuánez, Hector N; Horvath, Julie E; Moreira, Miguel A M; Kessing, Bailey; Pontius, Joan; Roelke, Melody; Rumpler, Yves; Schneider, Maria Paula C; Silva, Artur; O'Brien, Stephen J; Pecon-Slattery, Jill

2011-03-01

Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb) from 186 primates representing 61 (~90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species.

A Molecular Phylogeny of Living Primates

Science.gov (United States)

Perelman, Polina; Johnson, Warren E.; Roos, Christian; Seuánez, Hector N.; Horvath, Julie E.; Moreira, Miguel A. M.; Kessing, Bailey; Pontius, Joan; Roelke, Melody; Rumpler, Yves; Schneider, Maria Paula C.; Silva, Artur; O'Brien, Stephen J.; Pecon-Slattery, Jill

2011-01-01

Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (∼8 Mb) from 186 primates representing 61 (∼90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species. PMID:21436896

A molecular phylogeny of living primates.

Directory of Open Access Journals (Sweden)

Polina Perelman

2011-03-01

Full Text Available Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb from 186 primates representing 61 (~90% of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species.

Raptors and primate evolution.

Science.gov (United States)

McGraw, W Scott; Berger, Lee R

2013-01-01

Most scholars agree that avoiding predators is a central concern of lemurs, monkeys, and apes. However, given uncertainties about the frequency with which primates actually become prey, the selective importance of predation in primate evolution continues to be debated. Some argue that primates are often killed by predators, while others maintain that such events are relatively rare. Some authors have contended that predation's influence on primate sociality has been trivial; others counter that predation need not occur often to be a powerful selective force. Given the challenges of documenting events that can be ephemeral and irregular, we are unlikely ever to amass the volume of systematic, comparative data we have on such topics as feeding, social dynamics, or locomotor behavior. Nevertheless, a steady accumulation of field observations, insight gained from natural experiments, and novel taphonomic analyses have enhanced understanding of how primates interact with several predators, especially raptors, the subject of this review. Copyright © 2013 Wiley Periodicals, Inc.

Characteristics of primary infection of a European human immunodeficiency virus type 1 clade B isolate in chimpanzees

NARCIS (Netherlands)

Bogers, W. M.; Koornstra, W. H.; Dubbes, R. H.; ten Haaft, P. J.; Verstrepen, B. E.; Jhagjhoorsingh, S. S.; Haaksma, A. G.; Niphuis, H.; Laman, J. D.; Norley, S.; Schuitemaker, H.; Goudsmit, J.; Hunsmann, G.; Heeney, J. L.; Wigzell, H.

1998-01-01

The aim of the study was to select, from a panel of candidate European human immunodeficiency virus type 1 (HIV-1) clade B primary virus isolates, one isolate based on replication properties in chimpanzee peripheral blood mononuclear cells (PBMC). Secondly, to evaluate the in vivo kinetics of

Suppression of Coronavirus Replication by Cyclophilin Inhibitors

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Takashi Sasaki

2013-05-01

Full Text Available Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS, feline infectious peritonitis (FIP, mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA, could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.

Optimization of the doxycycline-dependent simian immunodeficiency virus through in vitro evolution

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Piatak Mike

2008-06-01

Full Text Available Abstract Background Vaccination of macaques with live attenuated simian immunodeficiency virus (SIV provides significant protection against the wild-type virus. The use of a live attenuated human immunodeficiency virus (HIV as AIDS vaccine in humans is however considered unsafe because of the risk that the attenuated virus may accumulate genetic changes during persistence and evolve to a pathogenic variant. We earlier presented a conditionally live HIV-1 variant that replicates exclusively in the presence of doxycycline (dox. Replication of this vaccine strain can be limited to the time that is needed to provide full protection through transient dox administration. Since the effectiveness and safety of such a conditionally live virus vaccine should be tested in macaques, we constructed a similar dox-dependent SIV variant. The Tat-TAR transcription control mechanism in this virus was inactivated through mutation and functionally replaced by the dox-inducible Tet-On regulatory system. This SIV-rtTA variant replicated in a dox-dependent manner in T cell lines, but not as efficiently as the parental SIVmac239 strain. Since macaque studies will likely require an efficiently replicating variant, we set out to optimize SIV-rtTA through in vitro viral evolution. Results Upon long-term culturing of SIV-rtTA, additional nucleotide substitutions were observed in TAR that affect the structure of this RNA element but that do not restore Tat binding. We demonstrate that the bulge and loop mutations that we had introduced in the TAR element of SIV-rtTA to inactivate the Tat-TAR mechanism, shifted the equilibrium between two alternative conformations of TAR. The additional TAR mutations observed in the evolved variants partially or completely restored this equilibrium, which suggests that the balance between the two TAR conformations is important for efficient viral replication. Moreover, SIV-rtTA acquired mutations in the U3 promoter region. We demonstrate

An integrated chemical biology approach reveals the mechanism of action of HIV replication inhibitors.

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Pagano, Nicholas; Teriete, Peter; Mattmann, Margrith E; Yang, Li; Snyder, Beth A; Cai, Zhaohui; Heil, Marintha L; Cosford, Nicholas D P

2017-12-01

Continuous flow (microfluidic) chemistry was employed to prepare a small focused library of dihydropyrimidinone (DHPM) derivatives. Compounds in this class have been reported to exhibit activity against the human immunodeficiency virus (HIV), but their molecular target had not been identified. We tested the initial set of DHPMs in phenotypic assays providing a hit (1i) that inhibited the replication of the human immunodeficiency virus HIV in cells. Flow chemistry-driven optimization of 1i led to the identification of HIV replication inhibitors such as 1l with cellular potency comparable with the clinical drug nevirapine (NVP). Mechanism of action (MOA) studies using cellular and biochemical assays coupled with 3D fingerprinting and in silico modeling demonstrated that these drug-like probe compounds exert their effects by inhibiting the viral reverse transcriptase polymerase (RT). This led to the design and synthesis of the novel DHPM 1at that inhibits the replication of drug resistant strains of HIV. Our work demonstrates that combining flow chemistry-driven analogue refinement with phenotypic assays, in silico modeling and MOA studies is a highly effective strategy for hit-to-lead optimization applicable to the discovery of future therapeutic agents. Copyright © 2017. Published by Elsevier Ltd.

The Molecular Biology of Feline Immunodeficiency Virus (FIV

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Andrew M. L. Lever

2011-11-01

Full Text Available Feline immunodeficiency virus (FIV is widespread in feline populations and causes an AIDS-like illness in domestic cats. It is highly prevalent in several endangered feline species. In domestic cats FIV infection is a valuable small animal model for HIV infection. In recent years there has been a significant increase in interest in FIV, in part to exploit this, but also because of the potential it has as a human gene therapy vector. Though much less studied than HIV there are many parallels in the replication of the two viruses, but also important differences and, despite their likely common origin, the viruses have in some cases used alternative strategies to overcome similar problems. Recent advances in understanding the structure and function of FIV RNA and proteins and their interactions has enhanced our knowledge of FIV replication significantly, however, there are still many gaps. This review summarizes our current knowledge of FIV molecular biology and its similarities with, and differences from, other lentiviruses.

The molecular biology of feline immunodeficiency virus (FIV).

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Kenyon, Julia C; Lever, Andrew M L

2011-11-01

Feline immunodeficiency virus (FIV) is widespread in feline populations and causes an AIDS-like illness in domestic cats. It is highly prevalent in several endangered feline species. In domestic cats FIV infection is a valuable small animal model for HIV infection. In recent years there has been sa significant increase in interest in FIV, in part to exploit this, but also because of the potential it has as a human gene therapy vector. Though much less studied than HIV there are many parallels in the replication of the two viruses, but also important differences and, despite their likely common origin, the viruses have in some cases used alternative strategies to overcome similar problems. Recent advances in understanding the structure and function of FIV RNA and proteins and their interactions has enhanced our knowledge of FIV replication significantly, however, there are still many gaps. This review summarizes our current knowledge of FIV molecular biology and its similarities with, and differences from, other lentiviruses.

The evolution of neocortex in primates.

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Kaas, Jon H

2012-01-01

We can learn about the evolution of neocortex in primates through comparative studies of cortical organization in primates and those mammals that are the closest living relatives of primates, in conjunction with brain features revealed by the skull endocasts of fossil archaic primates. Such studies suggest that early primates had acquired a number of features of neocortex that now distinguish modern primates. Most notably, early primates had an array of new visual areas, and those visual areas widely shared with other mammals had been modified. Posterior parietal cortex was greatly expanded with sensorimotor modules for reaching, grasping, and personal defense. Motor cortex had become more specialized for hand use, and the functions of primary motor cortex were enhanced by the addition and development of premotor and cingulate motor areas. Cortical architecture became more varied, and cortical neuron populations became denser overall than in nonprimate ancestors. Primary visual cortex had the densest population of neurons, and this became more pronounced in the anthropoid radiation. Within the primate clade, considerable variability in cortical size, numbers of areas, and architecture evolved. Copyright © 2012 Elsevier B.V. All rights reserved.

The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication.

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Hill-Batorski, Lindsay; Halfmann, Peter; Neumann, Gabriele; Kawaoka, Yoshihiro

2013-12-01

Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection.

2',3'-Dideoxycytidine and human immunodeficiency virus reverse transcriptase

International Nuclear Information System (INIS)

Starnes, M.C.

1988-01-01

2',3'-Dideoxycytidine (ddCyd) is a candidate for clinical trial in the treatment of Acquired Immunodeficiency Syndrome, as a result of its potent inhibition of Human Immunodeficiency Virus (HIV) replication. The cellular metabolism and cytotoxicity of ddCyd are, as well as the interaction of ddCTP and other nucleotide and pyrophosphate analogs with mammalian DNA polymerases and HIV reverse transcriptase (RT). In addition, some structural and functional characteristics of HIV RT are described. 5 μM ddCyd reduced Molt 4 cell division by 50% during a 48 h continuous exposure; however, a 24 h exposure to 0.5 μM ddCyd reduced clonogenic survival by 50%. [ 14 C]-dThd incorporation into DNA was reduced during exposure to ddCyd. Acid-soluble ddCyd metabolites were ddCMP, ddCDP, and ddCTP. Initial ddCyd phosphorylation was catalyzed primarily by cytoplasmic dCyd kinase, and ddCyd was not a substrate for human Cyd-dCyd deaminase. Metabolism of ddCyd was identical in mock and HIV infected H9 cells

Secondary expansion of the transient subplate zone in the developing cerebrum of human and nonhuman primates

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Duque, Alvaro; Krsnik, Zeljka; Kostović, Ivica; Rakic, Pasko

2016-01-01

The subplate (SP) was the last cellular compartment added to the Boulder Committee’s list of transient embryonic zones [Bystron I, Blakemore C, Rakic P (2008) Nature Rev Neurosci 9(2):110–122]. It is highly developed in human and nonhuman primates, but its origin, mode, and dynamics of development, resolution, and eventual extinction are not well understood because human postmortem tissue offers only static descriptive data, and mice cannot serve as an adequate experimental model for the distinct regional differences in primates. Here, we take advantage of the large and slowly developing SP in macaque monkey to examine the origin, settling pattern, and subsequent dispersion of the SP neurons in primates. Monkey embryos exposed to the radioactive DNA replication marker tritiated thymidine ([3H]dT, or TdR) at early embryonic ages were killed at different intervals postinjection to follow postmitotic cells' positional changes. As expected in primates, most SP neurons generated in the ventricular zone initially migrate radially, together with prospective layer 6 neurons. Surprisingly, mostly during midgestation, SP cells become secondarily displaced and widespread into the expanding SP zone, which becomes particularly wide subjacent to the association cortical areas and underneath the summit of its folia. We found that invasion of monoamine, basal forebrain, thalamocortical, and corticocortical axons is mainly responsible for this region-dependent passive dispersion of the SP cells. Histologic and immunohistochemical comparison with the human SP at corresponding fetal ages indicates that the same developmental events occur in both primate species. PMID:27503885

Formation of RNA Granule-Derived Capsid Assembly Intermediates Appears To Be Conserved between Human Immunodeficiency Virus Type 1 and the Nonprimate Lentivirus Feline Immunodeficiency Virus.

Science.gov (United States)

Reed, Jonathan C; Westergreen, Nick; Barajas, Brook C; Ressler, Dylan T B; Phuong, Daryl J; Swain, John V; Lingappa, Vishwanath R; Lingappa, Jaisri R

2018-05-01

During immature capsid assembly in cells, human immunodeficiency virus type 1 (HIV-1) Gag co-opts a host RNA granule, forming a pathway of intracellular assembly intermediates containing host components, including two cellular facilitators of assembly, ABCE1 and DDX6. A similar assembly pathway has been observed for other primate lentiviruses. Here we asked whether feline immunodeficiency virus (FIV), a nonprimate lentivirus, also forms RNA granule-derived capsid assembly intermediates. First, we showed that the released FIV immature capsid and a large FIV Gag-containing intracellular complex are unstable during analysis, unlike for HIV-1. We identified harvest conditions, including in situ cross-linking, that overcame this problem, revealing a series of FIV Gag-containing complexes corresponding in size to HIV-1 assembly intermediates. Previously, we showed that assembly-defective HIV-1 Gag mutants are arrested at specific assembly intermediates; here we identified four assembly-defective FIV Gag mutants, including three not previously studied, and demonstrated that they appear to be arrested at the same intermediate as the cognate HIV-1 mutants. Further evidence that these FIV Gag-containing complexes correspond to assembly intermediates came from coimmunoprecipitations demonstrating that endogenous ABCE1 and the RNA granule protein DDX6 are associated with FIV Gag, as shown previously for HIV-1 Gag, but are not associated with a ribosomal protein, at steady state. Additionally, we showed that FIV Gag associates with another RNA granule protein, DCP2. Finally, we validated the FIV Gag-ABCE1 and FIV Gag-DCP2 interactions with proximity ligation assays demonstrating colocalization in situ Together, these data support a model in which primate and nonprimate lentiviruses form intracellular capsid assembly intermediates derived from nontranslating host RNA granules. IMPORTANCE Like HIV-1 Gag, FIV Gag assembles into immature capsids; however, it is not known whether

Hands of early primates.

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Boyer, Doug M; Yapuncich, Gabriel S; Chester, Stephen G B; Bloch, Jonathan I; Godinot, Marc

2013-12-01

Questions surrounding the origin and early evolution of primates continue to be the subject of debate. Though anatomy of the skull and inferred dietary shifts are often the focus, detailed studies of postcrania and inferred locomotor capabilities can also provide crucial data that advance understanding of transitions in early primate evolution. In particular, the hand skeleton includes characteristics thought to reflect foraging, locomotion, and posture. Here we review what is known about the early evolution of primate hands from a comparative perspective that incorporates data from the fossil record. Additionally, we provide new comparative data and documentation of skeletal morphology for Paleogene plesiadapiforms, notharctines, cercamoniines, adapines, and omomyiforms. Finally, we discuss implications of these data for understanding locomotor transitions during the origin and early evolutionary history of primates. Known plesiadapiform species cannot be differentiated from extant primates based on either intrinsic hand proportions or hand-to-body size proportions. Nonetheless, the presence of claws and a different metacarpophalangeal [corrected] joint form in plesiadapiforms indicate different grasping mechanics. Notharctines and cercamoniines have intrinsic hand proportions with extremely elongated proximal phalanges and digit rays relative to metacarpals, resembling tarsiers and galagos. But their hand-to-body size proportions are typical of many extant primates (unlike those of tarsiers, and possibly Teilhardina, which have extremely large hands). Non-adapine adapiforms and omomyids exhibit additional carpal features suggesting more limited dorsiflexion, greater ulnar deviation, and a more habitually divergent pollex than observed plesiadapiforms. Together, features differentiating adapiforms and omomyiforms from plesiadapiforms indicate increased reliance on vertical prehensile-clinging and grasp-leaping, possibly in combination with predatory behaviors in

42 CFR 71.53 - Nonhuman primates.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Nonhuman primates. 71.53 Section 71.53 Public... FOREIGN QUARANTINE Importations § 71.53 Nonhuman primates. (a) Definitions. As used in this section the... nonhuman primates from a foreign country within a period of 31 days, beginning with the importation date...

Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates.

Science.gov (United States)

Ault, Alida; Tennant, Sharon M; Gorres, J Patrick; Eckhaus, Michael; Sandler, Netanya G; Roque, Annelys; Livio, Sofie; Bao, Saran; Foulds, Kathryn E; Kao, Shing-Fen; Roederer, Mario; Schmidlein, Patrick; Boyd, Mary Adetinuke; Pasetti, Marcela F; Douek, Daniel C; Estes, Jacob D; Nabel, Gary J; Levine, Myron M; Rao, Srinivas S

2013-12-02

Nontyphoidal Salmonella (NTS) serovars are a common cause of acute food-borne gastroenteritis worldwide and can cause invasive systemic disease in young infants, the elderly, and immunocompromised hosts, accompanied by high case fatality. Vaccination against invasive NTS disease is warranted where the disease incidence and mortality are high and multidrug resistance is prevalent, as in sub-Saharan Africa. Live-attenuated vaccines that mimic natural infection constitute one strategy to elicit protection. However, they must particularly be shown to be adequately attenuated for consideration of immunocompromised subjects. Accordingly, we examined the safety and tolerability of an oral live attenuated Salmonella typhimurium vaccine candidate, CVD 1921, in an established chronic simian immunodeficiency virus (SIV)-infected rhesus macaque model. We evaluated clinical parameters, histopathology, and measured differences in mucosal permeability to wild-type and vaccine strains. Compared to the wild-type S. typhimurium strain I77 in both SIV-infected and SIV-uninfected nonhuman primate hosts, this live-attenuated vaccine shows reduced shedding and systemic spread, exhibits limited pathological disease manifestations in the digestive tract, and induces low levels of cellular infiltration in tissues. Furthermore, wild-type S. typhimurium induces increased intestinal epithelial damage and permeability, with infiltration of neutrophils and macrophages in both SIV-infected and SIV-uninfected nonhuman primates compared to the vaccine strain. Based on shedding, systemic spread, and histopathology, the live-attenuated S. typhimurium strain CVD 1921 appears to be safe and well-tolerated in the nonhuman primate model, including chronically SIV-infected rhesus macaques. Copyright © 2013. Published by Elsevier Ltd.

Primates in peril: the significance of Brazil, Madagascar, Indonesia and the Democratic Republic of the Congo for global primate conservation

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Mittermeier, Russell A.; Wich, Serge; Gouveia, Sidney; Dobrovolski, Ricardo; Nijman, Vincent; Rylands, Anthony B.; Johnson, Steig; Rodrigues de Melo, Fabiano; Schwitzer, Christoph; Roos, Christian; Cheyne, Susan M.; Martins Kierulff, Maria Cecilia; Raharivololona, Brigitte; Ratsimbazafy, Jonah; Supriatna, Jatna; Boonratana, Ramesh; Wedana, Made; Setiawan, Arif

2018-01-01

Primates occur in 90 countries, but four—Brazil, Madagascar, Indonesia, and the Democratic Republic of the Congo (DRC)—harbor 65% of the world’s primate species (439) and 60% of these primates are Threatened, Endangered, or Critically Endangered (IUCN Red List of Threatened Species 2017-3). Considering their importance for global primate conservation, we examine the anthropogenic pressures each country is facing that place their primate populations at risk. Habitat loss and fragmentation are main threats to primates in Brazil, Madagascar, and Indonesia. However, in DRC hunting for the commercial bushmeat trade is the primary threat. Encroachment on primate habitats driven by local and global market demands for food and non-food commodities hunting, illegal trade, the proliferation of invasive species, and human and domestic-animal borne infectious diseases cause habitat loss, population declines, and extirpation. Modeling agricultural expansion in the 21st century for the four countries under a worst-case-scenario, showed a primate range contraction of 78% for Brazil, 72% for Indonesia, 62% for Madagascar, and 32% for DRC. These pressures unfold in the context of expanding human populations with low levels of development. Weak governance across these four countries may limit effective primate conservation planning. We examine landscape and local approaches to effective primate conservation policies and assess the distribution of protected areas and primates in each country. Primates in Brazil and Madagascar have 38% of their range inside protected areas, 17% in Indonesia and 14% in DRC, suggesting that the great majority of primate populations remain vulnerable. We list the key challenges faced by the four countries to avert primate extinctions now and in the future. In the short term, effective law enforcement to stop illegal hunting and illegal forest destruction is absolutely key. Long-term success can only be achieved by focusing local and global public

Primates in peril: the significance of Brazil, Madagascar, Indonesia and the Democratic Republic of the Congo for global primate conservation.

Science.gov (United States)

Estrada, Alejandro; Garber, Paul A; Mittermeier, Russell A; Wich, Serge; Gouveia, Sidney; Dobrovolski, Ricardo; Nekaris, K A I; Nijman, Vincent; Rylands, Anthony B; Maisels, Fiona; Williamson, Elizabeth A; Bicca-Marques, Julio; Fuentes, Agustin; Jerusalinsky, Leandro; Johnson, Steig; Rodrigues de Melo, Fabiano; Oliveira, Leonardo; Schwitzer, Christoph; Roos, Christian; Cheyne, Susan M; Martins Kierulff, Maria Cecilia; Raharivololona, Brigitte; Talebi, Mauricio; Ratsimbazafy, Jonah; Supriatna, Jatna; Boonratana, Ramesh; Wedana, Made; Setiawan, Arif

2018-01-01

Primates occur in 90 countries, but four-Brazil, Madagascar, Indonesia, and the Democratic Republic of the Congo (DRC)-harbor 65% of the world's primate species (439) and 60% of these primates are Threatened, Endangered, or Critically Endangered (IUCN Red List of Threatened Species 2017-3). Considering their importance for global primate conservation, we examine the anthropogenic pressures each country is facing that place their primate populations at risk. Habitat loss and fragmentation are main threats to primates in Brazil, Madagascar, and Indonesia. However, in DRC hunting for the commercial bushmeat trade is the primary threat. Encroachment on primate habitats driven by local and global market demands for food and non-food commodities hunting, illegal trade, the proliferation of invasive species, and human and domestic-animal borne infectious diseases cause habitat loss, population declines, and extirpation. Modeling agricultural expansion in the 21st century for the four countries under a worst-case-scenario, showed a primate range contraction of 78% for Brazil, 72% for Indonesia, 62% for Madagascar, and 32% for DRC. These pressures unfold in the context of expanding human populations with low levels of development. Weak governance across these four countries may limit effective primate conservation planning. We examine landscape and local approaches to effective primate conservation policies and assess the distribution of protected areas and primates in each country. Primates in Brazil and Madagascar have 38% of their range inside protected areas, 17% in Indonesia and 14% in DRC, suggesting that the great majority of primate populations remain vulnerable. We list the key challenges faced by the four countries to avert primate extinctions now and in the future. In the short term, effective law enforcement to stop illegal hunting and illegal forest destruction is absolutely key. Long-term success can only be achieved by focusing local and global public

78 FR 29755 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

Science.gov (United States)

2013-05-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure... an opportunity for public comment on human immunodeficiency virus (HIV) Patient-Focused Drug...

A Mitogenomic Phylogeny of Living Primates

Science.gov (United States)

Finstermeier, Knut; Zinner, Dietmar; Brameier, Markus; Meyer, Matthias; Kreuz, Eva; Hofreiter, Michael; Roos, Christian

2013-01-01

Primates, the mammalian order including our own species, comprise 480 species in 78 genera. Thus, they represent the third largest of the 18 orders of eutherian mammals. Although recent phylogenetic studies on primates are increasingly built on molecular datasets, most of these studies have focused on taxonomic subgroups within the order. Complete mitochondrial (mt) genomes have proven to be extremely useful in deciphering within-order relationships even up to deep nodes. Using 454 sequencing, we sequenced 32 new complete mt genomes adding 20 previously not represented genera to the phylogenetic reconstruction of the primate tree. With 13 new sequences, the number of complete mt genomes within the parvorder Platyrrhini was widely extended, resulting in a largely resolved branching pattern among New World monkey families. We added 10 new Strepsirrhini mt genomes to the 15 previously available ones, thus almost doubling the number of mt genomes within this clade. Our data allow precise date estimates of all nodes and offer new insights into primate evolution. One major result is a relatively young date for the most recent common ancestor of all living primates which was estimated to 66-69 million years ago, suggesting that the divergence of extant primates started close to the K/T-boundary. Although some relationships remain unclear, the large number of mt genomes used allowed us to reconstruct a robust primate phylogeny which is largely in agreement with previous publications. Finally, we show that mt genomes are a useful tool for resolving primate phylogenetic relationships on various taxonomic levels. PMID:23874967

78 FR 46969 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

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2013-08-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure... for the notice of public meeting entitled ``Human Immunodeficiency Virus (HIV) Patient-Focused Drug...

Property in Nonhuman Primates

Science.gov (United States)

Brosnan, Sarah F.

2011-01-01

Property is rare in most nonhuman primates, most likely because their lifestyles are not conducive to it. Nonetheless, just because these species do not frequently maintain property does not mean that they lack the propensity to do so. Primates show respect for possession, as well as behaviors related to property, such as irrational decision…

Captivity humanizes the primate microbiome.

Science.gov (United States)

Clayton, Jonathan B; Vangay, Pajau; Huang, Hu; Ward, Tonya; Hillmann, Benjamin M; Al-Ghalith, Gabriel A; Travis, Dominic A; Long, Ha Thang; Tuan, Bui Van; Minh, Vo Van; Cabana, Francis; Nadler, Tilo; Toddes, Barbara; Murphy, Tami; Glander, Kenneth E; Johnson, Timothy J; Knights, Dan

2016-09-13

The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome.

Strategies for B-cell receptor repertoire analysis in Primary Immunodeficiencies:From severe combined immunodeficiency to common variable immunodeficiency

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Hanna eIJspeert

2015-04-01

Full Text Available The antigen receptor repertoires of B and T cells form the basis of the adaptive immune response. The repertoires should be sufficiently diverse to recognize all possible pathogens. However, careful selection is needed to prevent responses to self or harmless antigens. Limited antigen receptor repertoire diversity leads to immunodeficiency, whereas unselected or misdirected repertoires can result in autoimmunity. The antigen receptor repertoire harbors information about abnormalities in many immunological disorders. Recent developments in next generation sequencing allow the analysis of the antigen receptor repertoire in much greater detail than ever before. Analyzing the antigen receptor repertoire in patients with mutations in genes responsible for the generation of the antigen receptor repertoire will give new insights into repertoire formation and selection. In this perspective we describe strategies and considerations for analysis of the naive and antigen selected B-cell repertoires in primary immunodeficiency (PID patients with a focus on severe combined immunodeficiency (SCID and common variable immunodeficiency (CVID.

Vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates.

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Thomas W Geisbert

2008-11-01

Full Text Available Ebola virus (EBOV is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVDeltaG/ZEBOVGP in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV. All six animals showed no evidence of illness associated with the VSVDeltaG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV.

Vif of Feline Immunodeficiency Virus from Domestic Cats Protects against APOBEC3 Restriction Factors from Many Felids▿

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Zielonka, Jörg; Marino, Daniela; Hofmann, Henning; Yuhki, Naoya; Löchelt, Martin; Münk, Carsten

2010-01-01

To get more insight into the role of APOBEC3 (A3) cytidine deaminases in the species-specific restriction of feline immunodeficiency virus (FIV) of the domestic cat, we tested the A3 proteins present in big cats (puma, lion, tiger, and lynx). These A3 proteins were analyzed for expression and sensitivity to the Vif protein of FIV. While A3Z3s and A3Z2-Z3s inhibited Δvif FIV, felid A3Z2s did not show any antiviral activity against Δvif FIV or wild-type (wt) FIV. All felid A3Z3s and A3Z2-Z3s were sensitive to Vif of the domestic cat FIV. Vif also induced depletion of felid A3Z2s. Tiger A3s showed a moderate degree of resistance against the Vif-mediated counter defense. These findings may imply that the A3 restriction system does not play a major role to prevent domestic cat FIV transmission to other Felidae. In contrast to the sensitive felid A3s, many nonfelid A3s actively restricted wt FIV replication. To test whether VifFIV can protect also the distantly related human immunodeficiency virus type 1 (HIV-1), a chimeric HIV-1.VifFIV was constructed. This HIV-1.VifFIV was replication competent in nonpermissive feline cells expressing human CD4/CCR5 that did not support the replication of wt HIV-1. We conclude that the replication of HIV-1 in some feline cells is inhibited only by feline A3 restriction factors and the absence of the appropriate receptor or coreceptor. PMID:20444897

Vif of feline immunodeficiency virus from domestic cats protects against APOBEC3 restriction factors from many felids.

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Zielonka, Jörg; Marino, Daniela; Hofmann, Henning; Yuhki, Naoya; Löchelt, Martin; Münk, Carsten

2010-07-01

To get more insight into the role of APOBEC3 (A3) cytidine deaminases in the species-specific restriction of feline immunodeficiency virus (FIV) of the domestic cat, we tested the A3 proteins present in big cats (puma, lion, tiger, and lynx). These A3 proteins were analyzed for expression and sensitivity to the Vif protein of FIV. While A3Z3s and A3Z2-Z3s inhibited Deltavif FIV, felid A3Z2s did not show any antiviral activity against Deltavif FIV or wild-type (wt) FIV. All felid A3Z3s and A3Z2-Z3s were sensitive to Vif of the domestic cat FIV. Vif also induced depletion of felid A3Z2s. Tiger A3s showed a moderate degree of resistance against the Vif-mediated counter defense. These findings may imply that the A3 restriction system does not play a major role to prevent domestic cat FIV transmission to other Felidae. In contrast to the sensitive felid A3s, many nonfelid A3s actively restricted wt FIV replication. To test whether Vif(FIV) can protect also the distantly related human immunodeficiency virus type 1 (HIV-1), a chimeric HIV-1.Vif(FIV) was constructed. This HIV-1.Vif(FIV) was replication competent in nonpermissive feline cells expressing human CD4/CCR5 that did not support the replication of wt HIV-1. We conclude that the replication of HIV-1 in some feline cells is inhibited only by feline A3 restriction factors and the absence of the appropriate receptor or coreceptor.

Perceptions of nonhuman primates in human-wildlife conflict scenarios.

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Hill, Catherine M; Webber, Amanda D

2010-09-01

Nonhuman primates (referred to as primates in this study) are sometimes revered as gods, abhorred as evil spirits, killed for food because they damage crops, or butchered for sport. Primates' perceived similarity to humans places them in an anomalous position. While some human groups accept the idea that primates "straddle" the human-nonhuman boundary, for others this resemblance is a violation of the human-animal divide. In this study we use two case studies to explore how people's perceptions of primates are often influenced by these animals' apparent similarity to humans, creating expectations, founded within a "human morality" about how primates should interact with people. When animals transgress these social rules, they are measured against the same moral framework as humans. This has implications for how people view and respond to certain kinds of primate behaviors, their willingness to tolerate co-existence with primates and their likely support for primate conservation initiatives. 2010 Wiley-Liss, Inc.

SIVdrl detection in captive mandrills: are mandrills infected with a third strain of simian immunodeficiency virus?

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Osterhaus Albert DME

2004-11-01

Full Text Available Abstract A pol-fragment of simian immunodeficiency virus (SIV that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus was detected in two mandrills (Mandrillus sphinx from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely to be hybrids. Their mitochondrial haplotype suggested that they descended from founder animals in Cameroon or northern Gabon, close to the habitat of the drill. SIVdrl has once before been found in a wild-caught mandrill from the same region, indicating that mandrills are naturally infected with a SIVdrl-like virus. This suggests that mandrills are the first primate species to be infected with three strains of SIV: SIVmnd1, SIVmnd2, and SIVdrl.

Social knowledge and signals in primates.

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Bergman, Thore J; Sheehan, Michael J

2013-07-01

Primates are notable for having a rich and detailed understanding of their social environment and there has been great interest in the evolution and function of social knowledge in primates. Indeed, primates have been shown to have impressive understandings of not only other group members but also the complex relationships among them. To be useful, however, social knowledge requires memories from previous encounters and observations about individual traits that are stable. Here, we argue that social systems or traits that make social knowledge more costly or less accurate will favor signals that either supplement or replace social knowledge. Thus, the relationship between signals and social knowledge can be complementary or antagonistic depending on the type of signal. Our goal in this review is to elucidate the relationships between signals and social knowledge in primates. We categorize signals into three types, each with different relationships to social knowledge. (1) Identity signals directly facilitate social knowledge, (2) current-state signals supplement information gained through social knowledge, and (3) badges of status replace social knowledge. Primates rely extensively on identity information, but it remains to be determined to what extent this is based on receiver perception of individual variation or senders using identity signals. Primates frequently utilize current-state signals including signals of intent to augment their interactions with familiar individuals. Badges of status are rare in primates, and the cases where they are used point to a functional and evolutionary trade-off between badges of status and social knowledge. However, the nature of this relationship needs further exploration. © 2012 Wiley Periodicals, Inc.

Special issue: Comparative biogeography of Neotropical primates.

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Lynch Alfaro, Jessica W; Cortés-Ortiz, Liliana; Di Fiore, Anthony; Boubli, Jean P

2015-01-01

New research presented in this special issue of Molecular Phylogenetics and Evolution on the "Phylogeny and Biogeography of Neotropical Primates" greatly improves our understanding of the evolutionary history of the New World monkeys and provides insights into the multiple platyrrhine radiations, diversifications, extinctions, and recolonizations that have taken place over time and over space in the Neotropics. Here, we synthesize genetic and biogeographic research from the past several years to construct an overarching hypothesis for platyrrhine evolution. We also highlight continuing controversies in Neotropical primate biogeography, such as whether the location of origin of platyrrhines was Africa or Asia; whether Patagonian fossil primates are stem or crown platyrrhines; and whether cis- and trans-Andean Neotropical primates were subject to vicariance through Andes mountain building, or instead diversified through isolation in mountain valleys after skirting around the Andes on the northwestern coast of South America. We also consider the role of the Amazon River and its major tributaries in shaping platyrrhine biodiversity, and how and when primates from the Amazon reached the Atlantic Forest. A key focus is on primate colonizations and extirpations in Central America, the Andes, and the seasonally dry tropical forests and savannas (such as the Llanos, Caatinga, and Cerrado habitats), all ecosystems that have been understudied up until now for primates. We suggest that most primates currently inhabiting drier open habitats are relatively recent arrivals, having expanded from rainforest habitats in the Pleistocene. We point to the Pitheciidae as the taxonomic group most in need of further phylogenetic and biogeographic research. Additionally, genomic studies on the Platyrrhini are deeply needed and are expected to bring new surprises and insights to the field of Neotropical primate biogeography. Copyright © 2014 Elsevier Inc. All rights reserved.

A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates.

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Sha, Jian; Kirtley, Michelle L; Klages, Curtis; Erova, Tatiana E; Telepnev, Maxim; Ponnusamy, Duraisamy; Fitts, Eric C; Baze, Wallace B; Sivasubramani, Satheesh K; Lawrence, William S; Patrikeev, Igor; Peel, Jennifer E; Andersson, Jourdan A; Kozlova, Elena V; Tiner, Bethany L; Peterson, Johnny W; McWilliams, David; Patel, Snehal; Rothe, Eric; Motin, Vladimir L; Chopra, Ashok K

2016-07-01

Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Conserved residues in the coiled-coil pocket of human immunodeficiency virus type 1 gp41 are essential for viral replication and interhelical interaction

International Nuclear Information System (INIS)

Mo Hongmei; Konstantinidis, Alex K.; Stewart, Kent D.; Dekhtyar, Tatyana; Ng, Teresa; Swift, Kerry; Matayoshi, Edmund D.; Kati, Warren; Kohlbrenner, William; Molla, Akhteruzzaman

2004-01-01

The human immunodeficiency virus type 1 (HIV-1) gp41 plays an important role in mediating the fusion of HIV with host cells. During the fusion process, three N-terminal helices and three C-terminal helices pack in an anti-parallel direction to form a six-helix bundle. X-ray crystallographic analysis of the gp41 core demonstrated that within each coiled-coil interface, there is a deep and large pocket, formed by a cluster of residues in the N-helix coiled-coil. In this report, we systematically analyzed the role of seven conserved residues that are either lining or packing this pocket on the infectivity and interhelical interaction using novel approaches. Our results show that residues L568, V570, W571, and K574 of the N-helix that are lining the side chain and right wall of the pocket are important for establishing a productive infection. Mutations V570A and W571A completely abolished replication, while replication of the L568A and K574A mutants was significantly attenuated relative to wild type. Similarly, residues W628, W631, and I635 of the C-helix that insert into the pocket are essential for infectivity. The impaired infectivity of these seven mutants is in part attributed to the loss in binding affinity of the interhelical interaction. Molecular modeling of the crystal structure of the coiled-coil further shows that alanine substitution of those residues disrupts the hydrophobic interaction between the N- and C-helix. These results suggest that the conserved residues in the coiled-coil domain play a key role in HIV infection and this coiled-coil pocket is a good target for development of inhibitors against HIV. In addition, our data indicate that the novel fluorescence polarization assay described in this study could be valuable in screening for inhibitors that block the interhelical interaction and HIV entry

Feline immunodeficiency virus OrfA alters gene expression of splicing factors and proteasome-ubiquitination proteins

International Nuclear Information System (INIS)

Sundstrom, Magnus; Chatterji, Udayan; Schaffer, Lana; Rozieres, Sohela de; Elder, John H.

2008-01-01

Expression of the feline immunodeficiency virus (FIV) accessory protein OrfA (or Orf2) is critical for efficient viral replication in lymphocytes, both in vitro and in vivo. OrfA has been reported to exhibit functions in common with the human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) accessory proteins Vpr and Tat, although the function of OrfA has not been fully explained. Here, we use microarray analysis to characterize how OrfA modulates the gene expression profile of T-lymphocytes. The primary IL-2-dependent T-cell line 104-C1 was transduced to express OrfA. Functional expression of OrfA was demonstrated by trans complementation of the OrfA-defective clone, FIV-34TF10. OrfA-expressing cells had a slightly reduced cell proliferation rate but did not exhibit any significant alteration in cell cycle distribution. Reverse-transcribed RNA from cells expressing green fluorescent protein (GFP) or GFP + OrfA were hybridized to Affymetrix HU133 Plus 2.0 microarray chips representing more than 47,000 genome-wide transcripts. By using two statistical approaches, 461 (Rank Products) and 277 (ANOVA) genes were identified as modulated by OrfA expression. The functional relevance of the differentially expressed genes was explored by Ingenuity Pathway Analysis. The analyses revealed alterations in genes critical for RNA post-transcriptional modifications and protein ubiquitination as the two most significant functional outcomes of OrfA expression. In these two groups, several subunits of the spliceosome, cellular splicing factors and family members of the proteasome-ubiquitination system were identified. These findings provide novel information on the versatile function of OrfA during FIV infection and indicate a fine-tuning mechanism of the cellular environment by OrfA to facilitate efficient FIV replication

Learning about Severe Combined Immunodeficiency (SCID)

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... immunodeficiency From The Journal of Allergy and Clinical Immunology Learning About Severe Combined Immunodeficiency (SCID) What is ... immunodeficiency From The Journal of Allergy and Clinical Immunology Get Email Updates Privacy Copyright Contact Accessibility Plug- ...

Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection

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Barbara Tavano

2017-03-01

Full Text Available The human immunodeficiency virus (HIV accesses the central nervous system (CNS early during infection, leading to HIV-associated cognitive impairment and establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory responses in different CNS regions in simian immunodeficiency virus (SIV-infected macaques, a model for HIV infection. We found increased expression of inflammatory genes and perivascular leukocyte infiltration in the midbrain of SIV-infected macaques. Conversely, the frontal lobe showed downregulation of inflammatory genes associated with interferon-γ and interleukin-6 pathways, and absence of perivascular cuffing. These immunologic alterations were not accompanied by differences in SIV transcriptional activity within the tissue. Altered expression of genes associated with neurotoxicity was observed in both midbrain and frontal lobe. The segregation of inflammatory responses to specific regions of the CNS may both account for HIV-associated neurological symptoms and constitute a critical hurdle for HIV eradication by shielding the CNS viral reservoir from antiviral immunity.

Contextualising primate origins--an ecomorphological framework.

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Soligo, Christophe; Smaers, Jeroen B

2016-04-01

Ecomorphology - the characterisation of the adaptive relationship between an organism's morphology and its ecological role - has long been central to theories of the origin and early evolution of the primate order. This is exemplified by two of the most influential theories of primate origins: Matt Cartmill's Visual Predation Hypothesis, and Bob Sussman's Angiosperm Co-Evolution Hypothesis. However, the study of primate origins is constrained by the absence of data directly documenting the events under investigation, and has to rely instead on a fragmentary fossil record and the methodological assumptions inherent in phylogenetic comparative analyses of extant species. These constraints introduce particular challenges for inferring the ecomorphology of primate origins, as morphology and environmental context must first be inferred before the relationship between the two can be considered. Fossils can be integrated in comparative analyses and observations of extant model species and laboratory experiments of form-function relationships are critical for the functional interpretation of the morphology of extinct species. Recent developments have led to important advancements, including phylogenetic comparative methods based on more realistic models of evolution, and improved methods for the inference of clade divergence times, as well as an improved fossil record. This contribution will review current perspectives on the origin and early evolution of primates, paying particular attention to their phylogenetic (including cladistic relationships and character evolution) and environmental (including chronology, geography, and physical environments) contextualisation, before attempting an up-to-date ecomorphological synthesis of primate origins. © 2016 Anatomical Society.

Relationship between current level of immunodeficiency and non-acquired immunodeficiency syndrome-defining malignancies

DEFF Research Database (Denmark)

Reekie, Joanne; Kosa, Csaba; Engsig, Frederik

2010-01-01

In the combined antiretroviral therapy (cART) era, non-acquired immunodeficiency syndrome (AIDS)-defining malignancies account for more morbidity and mortality in human immunodeficiency virus-infected patients than AIDS-defining malignancies. However, conflicting data have been reported...

Post-infection immunodeficiency virus control by neutralizing antibodies.

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Hiroyuki Yamamoto

Full Text Available BACKGROUND: Unlike most acute viral infections controlled with the appearance of virus-specific neutralizing antibodies (NAbs, primary HIV infections are not met with such potent and early antibody responses. This brings into question if or how the presence of potent antibodies can contribute to primary HIV control, but protective efficacies of antiviral antibodies in primary HIV infections have remained elusive; and, it has been speculated that even NAb induction could have only a limited suppressive effect on primary HIV replication once infection is established. Here, in an attempt to answer this question, we examined the effect of passive NAb immunization post-infection on primary viral replication in a macaque AIDS model. METHODS AND FINDINGS: The inoculums for passive immunization with simian immunodeficiency virus mac239 (SIVmac239-specific neutralizing activity were prepared by purifying polyclonal immunoglobulin G from pooled plasma of six SIVmac239-infected rhesus macaques with NAb induction in the chronic phase. Passive immunization of rhesus macaques with the NAbs at day 7 after SIVmac239 challenge resulted in significant reduction of set-point plasma viral loads and preservation of central memory CD4 T lymphocyte counts, despite the limited detection period of the administered NAb responses. Peripheral lymph node dendritic cell (DC-associated viral RNA loads showed a remarkable peak with the NAb administration, and DCs stimulated in vitro with NAb-preincubated SIV activated virus-specific CD4 T lymphocytes in an Fc-dependent manner, implying antibody-mediated virion uptake by DCs and enhanced T cell priming. CONCLUSIONS: Our results present evidence indicating that potent antibody induction post-infection can result in primary immunodeficiency virus control and suggest direct and indirect contribution of its absence to initial control failure in HIV infections. Although difficulty in achieving requisite neutralizing titers for

Common Variable Immunodeficiency Caused by FANC Mutations.

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Sekinaka, Yujin; Mitsuiki, Noriko; Imai, Kohsuke; Yabe, Miharu; Yabe, Hiromasa; Mitsui-Sekinaka, Kanako; Honma, Kenichi; Takagi, Masatoshi; Arai, Ayako; Yoshida, Kenichi; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Muramatsu, Hideki; Kojima, Seiji; Hira, Asuka; Takata, Minoru; Ohara, Osamu; Ogawa, Seishi; Morio, Tomohiro; Nonoyama, Shigeaki

2017-07-01

Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4 + T cells were skewed toward CD45RO + memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using WES, we identified compound heterozygous mutations of FANCE in one patient and homozygous mutation of FANCA in another patient. The impaired function of FANC protein complex was confirmed by a monoubiquitination assay and by chromosome fragility test. We then performed several immunological evaluations including quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have immunological abnormalities, suggesting that such immunological findings may be common in FA patients. These data indicate that FANC mutations are involved in impaired lymphogenesis probably by the accumulation of DNA replication stress, leading to CVID. It is important to diagnose FA because it drastically changes clinical management. We propose that FANC mutations can cause isolated immunodeficiency in addition to bone marrow failure and malignancy.

Primate malarias: Diversity, distribution and insights for zoonotic Plasmodium

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Christina Faust

2015-12-01

Full Text Available Protozoans within the genus Plasmodium are well-known as the causative agents of malaria in humans. Numerous Plasmodium species parasites also infect a wide range of non-human primate hosts in tropical and sub-tropical regions worldwide. Studying this diversity can provide critical insight into our understanding of human malarias, as several human malaria species are a result of host switches from non-human primates. Current spillover of a monkey malaria, Plasmodium knowlesi, in Southeast Asia highlights the permeability of species barriers in Plasmodium. Also recently, surveys of apes in Africa uncovered a previously undescribed diversity of Plasmodium in chimpanzees and gorillas. Therefore, we carried out a meta-analysis to quantify the global distribution, host range, and diversity of known non-human primate malaria species. We used published records of Plasmodium parasites found in non-human primates to estimate the total diversity of non-human primate malarias globally. We estimate that at least three undescribed primate malaria species exist in sampled primates, and many more likely exist in unstudied species. The diversity of malaria parasites is especially uncertain in regions of low sampling such as Madagascar, and taxonomic groups such as African Old World Monkeys and gibbons. Presence–absence data of malaria across primates enables us to highlight the close association of forested regions and non-human primate malarias. This distribution potentially reflects a long coevolution of primates, forest-adapted mosquitoes, and malaria parasites. The diversity and distribution of primate malaria are an essential prerequisite to understanding the mechanisms and circumstances that allow Plasmodium to jump species barriers, both in the evolution of malaria parasites and current cases of spillover into humans.

Measles vaccination of nonhuman primates provides partial protection against infection with canine distemper virus.

Science.gov (United States)

de Vries, Rory D; Ludlow, Martin; Verburgh, R Joyce; van Amerongen, Geert; Yüksel, Selma; Nguyen, D Tien; McQuaid, Stephen; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

2014-04-01

Measles virus (MV) is being considered for global eradication, which would likely reduce compliance with MV vaccination. As a result, children will grow up without MV-specific immunity, creating a potential niche for closely related animal morbilliviruses such as canine distemper virus (CDV). Natural CDV infection causing clinical signs has never been reported in humans, but recent outbreaks in captive macaques have shown that CDV can cause disease in primates. We studied the virulence and tropism of recombinant CDV expressing enhanced green fluorescent protein in naive and measles-vaccinated cynomolgus macaques. In naive animals CDV caused viremia and fever and predominantly infected CD150(+) lymphocytes and dendritic cells. Virus was reisolated from the upper and lower respiratory tracts, but infection of epithelial or neuronal cells was not detectable at the time points examined, and the infections were self-limiting. This demonstrates that CDV readily infects nonhuman primates but suggests that additional mutations are necessary to achieve full virulence in nonnatural hosts. Partial protection against CDV was observed in measles-vaccinated macaques, as demonstrated by accelerated control of virus replication and limited shedding from the upper respiratory tract. While neither CDV infection nor MV vaccination induced detectable cross-reactive neutralizing antibodies, MV-specific neutralizing antibody levels of MV-vaccinated macaques were boosted by CDV challenge infection, suggesting that cross-reactive VN epitopes exist. Rapid increases in white blood cell counts in MV-vaccinated macaques following CDV challenge suggested that cross-reactive cellular immune responses were also present. This study demonstrates that zoonotic morbillivirus infections can be controlled by measles vaccination. Throughout history viral zoonoses have had a substantial impact on human health. Given the drive toward global eradication of measles, it is essential to understand the

Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions.

Science.gov (United States)

Sengupta, Asmita; McConkey, Kim R; Radhakrishna, Sindhu

2015-01-01

Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice.

Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions.

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Asmita Sengupta

Full Text Available Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice.

Human Immune System Mice for the Study of Human Immunodeficiency Virus-Type 1 Infection of the Central Nervous System

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Evering, Teresa H.; Tsuji, Moriya

2018-01-01

Immunodeficient mice transplanted with human cell populations or tissues, also known as human immune system (HIS) mice, have emerged as an important and versatile tool for the in vivo study of human immunodeficiency virus-type 1 (HIV-1) pathogenesis, treatment, and persistence in various biological compartments. Recent work in HIS mice has demonstrated their ability to recapitulate critical aspects of human immune responses to HIV-1 infection, and such studies have informed our knowledge of HIV-1 persistence and latency in the context of combination antiretroviral therapy. The central nervous system (CNS) is a unique, immunologically privileged compartment susceptible to HIV-1 infection, replication, and immune-mediated damage. The unique, neural, and glia-rich cellular composition of this compartment, as well as the important role of infiltrating cells of the myeloid lineage in HIV-1 seeding and replication makes its study of paramount importance, particularly in the context of HIV-1 cure research. Current work on the replication and persistence of HIV-1 in the CNS, as well as cells of the myeloid lineage thought to be important in HIV-1 infection of this compartment, has been aided by the expanded use of these HIS mouse models. In this review, we describe the major HIS mouse models currently in use for the study of HIV-1 neuropathogenesis, recent insights from the field, limitations of the available models, and promising advances in HIS mouse model development. PMID:29670623

Sexual selection and the evolution of brain size in primates.

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Schillaci, Michael A

2006-12-20

Reproductive competition among males has long been considered a powerful force in the evolution of primates. The evolution of brain size and complexity in the Order Primates has been widely regarded as the hallmark of primate evolutionary history. Despite their importance to our understanding of primate evolution, the relationship between sexual selection and the evolutionary development of brain size is not well studied. The present research examines the evolutionary relationship between brain size and two components of primate sexual selection, sperm competition and male competition for mates. Results indicate that there is not a significant relationship between relative brain size and sperm competition as measured by relative testis size in primates, suggesting sperm competition has not played an important role in the evolution of brain size in the primate order. There is, however, a significant negative evolutionary relationship between relative brain size and the level of male competition for mates. The present study shows that the largest relative brain sizes among primate species are associated with monogamous mating systems, suggesting primate monogamy may require greater social acuity and abilities of deception.

B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers.

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Fukazawa, Yoshinori; Lum, Richard; Okoye, Afam A; Park, Haesun; Matsuda, Kenta; Bae, Jin Young; Hagen, Shoko I; Shoemaker, Rebecca; Deleage, Claire; Lucero, Carissa; Morcock, David; Swanson, Tonya; Legasse, Alfred W; Axthelm, Michael K; Hesselgesser, Joseph; Geleziunas, Romas; Hirsch, Vanessa M; Edlefsen, Paul T; Piatak, Michael; Estes, Jacob D; Lifson, Jeffrey D; Picker, Louis J

2015-02-01

Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4(+) follicular helper T (TFH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected TFH cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-TFH cells, with restriction of productive infection to TFH cells resuming upon CD8(+) T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8(+) T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.

Pathogenesis of varicelloviruses in primates.

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Ouwendijk, Werner J D; Verjans, Georges M G M

2015-01-01

Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue, simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and, although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Long-distance calls in Neotropical primates

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Oliveira Dilmar A.G.

2004-01-01

Full Text Available Long-distance calls are widespread among primates. Several studies concentrate on such calls in just one or in few species, while few studies have treated more general trends within the order. The common features that usually characterize these vocalizations are related to long-distance propagation of sounds. The proposed functions of primate long-distance calls can be divided into extragroup and intragroup ones. Extragroup functions relate to mate defense, mate attraction or resource defense, while intragroup functions involve group coordination or alarm. Among Neotropical primates, several species perform long-distance calls that seem more related to intragroup coordination, markedly in atelines. Callitrichids present long-distance calls that are employed both in intragroup coordination and intergroup contests or spacing. Examples of extragroup directed long-distance calls are the duets of titi monkeys and the roars and barks of howler monkeys. Considerable complexity and gradation exist in the long-distance call repertoires of some Neotropical primates, and female long-distance calls are probably more important in non-duetting species than usually thought. Future research must focus on larger trends in the evolution of primate long-distance calls, including the phylogeny of calling repertoires and the relationships between form and function in these signals.

Development of a model for marburgvirus based on severe-combined immunodeficiency mice

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Kalina Warren V

2007-10-01

Full Text Available Abstract The filoviruses, Ebola (EBOV and Marburg (MARV, cause a lethal hemorrhagic fever. Human isolates of MARV are not lethal to immmunocompetent adult mice and, to date, there are no reports of a mouse-adapted MARV model. Previously, a uniformly lethal EBOV-Zaire mouse-adapted virus was developed by performing 9 sequential passages in progressively older mice (suckling to adult. Evaluation of this model identified many similarities between infection in mice and nonhuman primates, including viral tropism for antigen-presenting cells, high viral titers in the spleen and liver, and an equivalent mean time to death. Existence of the EBOV mouse model has increased our understanding of host responses to filovirus infections and likely has accelerated the development of countermeasures, as it is one of the only hemorrhagic fever viruses that has multiple candidate vaccines and therapeutics. Here, we demonstrate that serially passaging liver homogenates from MARV-infected severe combined immunodeficient (scid mice was highly successful in reducing the time to death in scid mice from 50–70 days to 7–10 days after MARV-Ci67, -Musoke, or -Ravn challenge. We performed serial sampling studies to characterize the pathology of these scid mouse-adapted MARV strains. These scid mouse-adapted MARV models appear to have many similar properties as the MARV models previously developed in guinea pigs and nonhuman primates. Also, as shown here, the scid-adapted MARV mouse models can be used to evaluate the efficacy of candidate antiviral therapeutic molecules, such as phosphorodiamidate morpholino oligomers or antibodies.

HIV-1 Replication and the Cellular Eukaryotic Translation Apparatus

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Santiago Guerrero

2015-01-01

Full Text Available Eukaryotic translation is a complex process composed of three main steps: initiation, elongation, and termination. During infections by RNA- and DNA-viruses, the eukaryotic translation machinery is used to assure optimal viral protein synthesis. Human immunodeficiency virus type I (HIV-1 uses several non-canonical pathways to translate its own proteins, such as leaky scanning, frameshifting, shunt, and cap-independent mechanisms. Moreover, HIV-1 modulates the host translation machinery by targeting key translation factors and overcomes different cellular obstacles that affect protein translation. In this review, we describe how HIV-1 proteins target several components of the eukaryotic translation machinery, which consequently improves viral translation and replication.

Changes in soluble factor-mediated CD8+ cell-derived antiviral activity in cynomolgus macaques infected with simian immunodeficiency virus SIVmac251: relationship to biological markers of progression.

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Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

2006-01-01

Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of beta-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and alpha-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells.

Changes in Soluble Factor-Mediated CD8+ Cell-Derived Antiviral Activity in Cynomolgus Macaques Infected with Simian Immunodeficiency Virus SIVmac251: Relationship to Biological Markers of Progression†

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Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

2006-01-01

Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of β-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and α-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells. PMID:16352548

Sexual selection and the evolution of brain size in primates.

Directory of Open Access Journals (Sweden)

Michael A Schillaci

Full Text Available Reproductive competition among males has long been considered a powerful force in the evolution of primates. The evolution of brain size and complexity in the Order Primates has been widely regarded as the hallmark of primate evolutionary history. Despite their importance to our understanding of primate evolution, the relationship between sexual selection and the evolutionary development of brain size is not well studied. The present research examines the evolutionary relationship between brain size and two components of primate sexual selection, sperm competition and male competition for mates. Results indicate that there is not a significant relationship between relative brain size and sperm competition as measured by relative testis size in primates, suggesting sperm competition has not played an important role in the evolution of brain size in the primate order. There is, however, a significant negative evolutionary relationship between relative brain size and the level of male competition for mates. The present study shows that the largest relative brain sizes among primate species are associated with monogamous mating systems, suggesting primate monogamy may require greater social acuity and abilities of deception.

CXCR4 Is Required by a Nonprimate Lentivirus: Heterologous Expression of Feline Immunodeficiency Virus in Human, Rodent, and Feline Cells

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Poeschla, Eric M.; Looney, David J.

1998-01-01

A heterologous feline immunodeficiency virus (FIV) expression system permitted high-level expression of FIV proteins and efficient production of infectious FIV in human cells. These results identify the FIV U3 element as the sole restriction to the productive phase of replication in nonfeline cells. Heterologous FIV expression in a variety of human cell lines resulted in profuse syncytial lysis that was FIV env specific, CD4 independent, and restricted to cells that express CXCR4, the coreceptor for T-cell-line-adapted strains of human immunodeficiency virus. Stable expression of human CXCR4 in CXCR4-negative human and rodent cell lines resulted in extensive FIV Env-mediated, CXCR4-dependent cell fusion and infection. In feline cells, stable overexpression of human CXCR4 resulted in increased FIV infectivity and marked syncytium formation during FIV replication or after infection with FIV Env-expressing vectors. The use of CXCR4 is a fundamental feature of lentivirus biology independent of CD4 and a shared cellular link to infection and cytopathicity for distantly related lentiviruses that cause AIDS. Their conserved use implicates chemokine receptors as primordial lentivirus receptors. PMID:9658135

[Diversity and development of positional behavior in non-human primates].

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Zhang, Jing; Qi, Xiao-Guang; Zhang, Kan; Zhang, Pei; Guo, Song-Tao; Wei, Wei; Li, Bao-Guo

2012-10-01

In long-term evolution, wildlife in general and primates in particular have formed specific patterns of behavior to adapt to a diverse variety of habitat environments. Current research on positional behavior in non-human primates has been found to explain a great deal about primate adaptability diversification, ecology, anatomy and evolution. Here, we summarize the noted classifications and differences in seasonal, site-specific and sex-age positional behaviors while also reviewing the development and status of non-human primate positional behavior research. This review is intended to provide reference for the future research of non-human primates and aid in further research on behavioral ecology of primates.

Loss of memory CD4+ T-cells in semi-wild mandrills (Mandrillus sphinx) naturally infected with species-specific simian immunodeficiency virus SIVmnd-1.

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Greenwood, Edward J D; Schmidt, Fabian; Liégeois, Florian; Kondova, Ivanela; Herbert, Anaïs; Ngoubangoye, Barthelemy; Rouet, François; Heeney, Jonathan L

2014-01-01

Simian immunodeficiency virus (SIV) infection is found in a number of African primate species and is thought to be generally non-pathogenic. However, studies of wild primates are limited to two species, with SIV infection appearing to have a considerably different outcome in each. Further examination of SIV-infected primates exposed to their natural environment is therefore warranted. We performed a large cross-sectional study of a cohort of semi-wild mandrills with naturally occurring SIV infection, including 39 SIV-negative and 33 species-specific SIVmnd-1-infected animals. This study was distinguished from previous reports by considerably greater sample size, examination of exclusively naturally infected animals in semi-wild conditions and consideration of simian T-lymphotropic virus (STLV) status in addition to SIVmnd-1 infection. We found that SIVmnd-1 infection was associated with a significant and progressive loss of memory CD4(+) T-cells. Limited but significant increases in markers of immune activation in the T-cell populations, significant increases in plasma neopterin and changes to B-cell subsets were also observed in SIV-infected animals. However, no increase in plasma soluble CD14 was observed. Histological examination of peripheral lymph nodes suggested that SIVmnd-1 infection was not associated with a significant disruption of the lymph node architecture. Whilst this species has evolved numerous strategies to resist the development of AIDS, significant effects of SIV infection could be observed when examined in a natural environment. STLVmnd-1 infection also had significant effects on some markers relevant to understanding SIV infection and thus should be considered in studies of SIV infection of African primates where present.

Ruxolitinib and Tofacitinib Are Potent and Selective Inhibitors of HIV-1 Replication and Virus Reactivation In Vitro

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Gavegnano, Christina; Detorio, Mervi; Montero, Catherine; Bosque, Alberto; Planelles, Vicente

2014-01-01

The JAK-STAT pathway is activated in both macrophages and lymphocytes upon human immunodeficiency virus type 1 (HIV-1) infection and thus represents an attractive cellular target to achieve HIV suppression and reduced inflammation, which may impact virus sanctuaries. Ruxolitinib and tofacitinib are JAK1/2 inhibitors that are FDA approved for rheumatoid arthritis and myelofibrosis, respectively, but their therapeutic application for treatment of HIV infection was unexplored. Both drugs demonstrated submicromolar inhibition of infection with HIV-1, HIV-2, and a simian-human immunodeficiency virus, RT-SHIV, across primary human or rhesus macaque lymphocytes and macrophages, with no apparent significant cytotoxicity at 2 to 3 logs above the median effective antiviral concentration. Combination of tofacitinib and ruxolitinib increased the efficacy by 53- to 161-fold versus that observed for monotherapy, respectively, and each drug applied alone to primary human lymphocytes displayed similar efficacy against HIV-1 containing various polymerase substitutions. Both drugs inhibited virus replication in lymphocytes stimulated with phytohemagglutinin (PHA) plus interleukin-2 (IL-2), but not PHA alone, and inhibited reactivation of latent HIV-1 at low-micromolar concentrations across the J-Lat T cell latency model and in primary human central memory lymphocytes. Thus, targeted inhibition of JAK provided a selective, potent, and novel mechanism to inhibit HIV-1 replication in lymphocytes and macrophages, replication of drug-resistant HIV-1, and reactivation of latent HIV-1 and has the potential to reset the immunologic milieu in HIV-infected individuals. PMID:24419350

Antibodies specific for hypervariable regions 3 to 5 of the feline immunodeficiency virus envelope glycoprotein are not solely responsible for vaccine-induced acceleration of challenge infection in cats

NARCIS (Netherlands)

W. Huisman (Willem); E.J.A. Schrauwen (Eefje); S.D. Pas (Suzan); J.A. Karlas (Jos); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

2004-01-01

textabstractIn a previous vaccination study in cats, the authors reported on accelerated feline immunodeficiency virus (FIV) replication upon challenge in animals vaccinated with a candidate envelope subunit vaccine. Plasma transfer studies as well as antibody profiles in vaccinated cats indicated a

Contributions of Nonhuman Primates to Research on Aging.

Science.gov (United States)

Didier, E S; MacLean, A G; Mohan, M; Didier, P J; Lackner, A A; Kuroda, M J

2016-03-01

Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements in public health, social services, and health care systems. Comparative studies among a wide range of organisms that include nonhuman primates contribute greatly to our understanding about the basic mechanisms of aging. Based on their genetic and physiologic relatedness to humans, nonhuman primates are especially important for better understanding processes of aging unique to primates, as well as for testing intervention strategies to improve healthy aging and to treat diseases and disabilities in older people. Rhesus and cynomolgus macaques are the predominant monkeys used in studies on aging, but research with lower nonhuman primate species is increasing. One of the priority topics of research about aging in nonhuman primates involves neurologic changes associated with cognitive decline and neurodegenerative diseases. Additional areas of research include osteoporosis, reproductive decline, caloric restriction, and their mimetics, as well as immune senescence and chronic inflammation that affect vaccine efficacy and resistance to infections and cancer. The purpose of this review is to highlight the findings from nonhuman primate research that contribute to our understanding about aging and health span in humans. © The Author(s) 2016.

Scaling of rotational inertia of primate mandibles.

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Ross, Callum F; Iriarte-Diaz, Jose; Platts, Ellen; Walsh, Treva; Heins, Liam; Gerstner, Geoffrey E; Taylor, Andrea B

2017-05-01

The relative importance of pendulum mechanics and muscle mechanics in chewing dynamics has implications for understanding the optimality criteria driving the evolution of primate feeding systems. The Spring Model (Ross et al., 2009b), which modeled the primate chewing system as a forced mass-spring system, predicted that chew cycle time would increase faster than was actually observed. We hypothesized that if mandibular momentum plays an important role in chewing dynamics, more accurate estimates of the rotational inertia of the mandible would improve the accuracy with which the Spring Model predicts the scaling of primate chew cycle period. However, if mass-related momentum effects are of negligible importance in the scaling of primate chew cycle period, this hypothesis would be falsified. We also predicted that greater "robusticity" of anthropoid mandibles compared with prosimians would be associated with higher moments of inertia. From computed tomography scans, we estimated the scaling of the moment of inertia (I j ) of the mandibles of thirty-one species of primates, including 22 anthropoid and nine prosimian species, separating I j into the moment about a transverse axis through the center of mass (I xx ) and the moment of the center of mass about plausible axes of rotation. We found that across primates I j increases with positive allometry relative to jaw length, primarily due to positive allometry of jaw mass and I xx , and that anthropoid mandibles have greater rotational inertia compared with prosimian mandibles of similar length. Positive allometry of I j of primate mandibles actually lowers the predictive ability of the Spring Model, suggesting that scaling of primate chew cycle period, and chewing dynamics in general, are more strongly influenced by factors other than scaling of inertial properties of the mandible, such as the dynamic properties of the jaw muscles and neural control. Differences in cycle period scaling between chewing and locomotion

Influenza Virus Infection in Nonhuman Primates

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Karlsson, Erik A.; Engel, Gregory A.; Feeroz, M.M.; San, Sorn; Rompis, Aida; Lee, Benjamin P. Y.-H.; Shaw, Eric; Oh, Gunwha; Schillaci, Michael A.; Grant, Richard; Heidrich, John; Schultz-Cherry, Stacey

2012-01-01

To determine whether nonhuman primates are infected with influenza viruses in nature, we conducted serologic and swab studies among macaques from several parts of the world. Our detection of influenza virus and antibodies to influenza virus raises questions about the role of nonhuman primates in the ecology of influenza. PMID:23017256

Mycobacterium leprae genomes from naturally infected nonhuman primates.

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Honap, Tanvi P; Pfister, Luz-Andrea; Housman, Genevieve; Mills, Sarah; Tarara, Ross P; Suzuki, Koichi; Cuozzo, Frank P; Sauther, Michelle L; Rosenberg, Michael S; Stone, Anne C

2018-01-01

Leprosy is caused by the bacterial pathogens Mycobacterium leprae and Mycobacterium lepromatosis. Apart from humans, animals such as nine-banded armadillos in the Americas and red squirrels in the British Isles are naturally infected with M. leprae. Natural leprosy has also been reported in certain nonhuman primates, but it is not known whether these occurrences are due to incidental infections by human M. leprae strains or by M. leprae strains specific to nonhuman primates. In this study, complete M. leprae genomes from three naturally infected nonhuman primates (a chimpanzee from Sierra Leone, a sooty mangabey from West Africa, and a cynomolgus macaque from The Philippines) were sequenced. Phylogenetic analyses showed that the cynomolgus macaque M. leprae strain is most closely related to a human M. leprae strain from New Caledonia, whereas the chimpanzee and sooty mangabey M. leprae strains belong to a human M. leprae lineage commonly found in West Africa. Additionally, samples from ring-tailed lemurs from the Bezà Mahafaly Special Reserve, Madagascar, and chimpanzees from Ngogo, Kibale National Park, Uganda, were screened using quantitative PCR assays, to assess the prevalence of M. leprae in wild nonhuman primates. However, these samples did not show evidence of M. leprae infection. Overall, this study adds genomic data for nonhuman primate M. leprae strains to the existing M. leprae literature and finds that this pathogen can be transmitted from humans to nonhuman primates as well as between nonhuman primate species. While the prevalence of natural leprosy in nonhuman primates is likely low, nevertheless, future studies should continue to explore the prevalence of leprosy-causing pathogens in the wild.

The adaptive value of primate color vision for predator detection.

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Pessoa, Daniel Marques Almeida; Maia, Rafael; de Albuquerque Ajuz, Rafael Cavalcanti; De Moraes, Pedro Zurvaino Palmeira Melo Rosa; Spyrides, Maria Helena Constantino; Pessoa, Valdir Filgueiras

2014-08-01

The complex evolution of primate color vision has puzzled biologists for decades. Primates are the only eutherian mammals that evolved an enhanced capacity for discriminating colors in the green-red part of the spectrum (trichromatism). However, while Old World primates present three types of cone pigments and are routinely trichromatic, most New World primates exhibit a color vision polymorphism, characterized by the occurrence of trichromatic and dichromatic females and obligatory dichromatic males. Even though this has stimulated a prolific line of inquiry, the selective forces and relative benefits influencing color vision evolution in primates are still under debate, with current explanations focusing almost exclusively at the advantages in finding food and detecting socio-sexual signals. Here, we evaluate a previously untested possibility, the adaptive value of primate color vision for predator detection. By combining color vision modeling data on New World and Old World primates, as well as behavioral information from human subjects, we demonstrate that primates exhibiting better color discrimination (trichromats) excel those displaying poorer color visions (dichromats) at detecting carnivoran predators against the green foliage background. The distribution of color vision found in extant anthropoid primates agrees with our results, and may be explained by the advantages of trichromats and dichromats in detecting predators and insects, respectively. © 2014 Wiley Periodicals, Inc.

Quality management for the international transportation of non-human primates

Directory of Open Access Journals (Sweden)

David B. Elmore

2008-03-01

Full Text Available Safe and humane transportation of live animals requires dedicated, informed personnel who carefully plan and attend to the details of appropriate animal care and handling throughout the shipping process. Specifically, although transportation of non-human primates shares goals common to all live animal transport, it also poses unique challenges stemming from the nature of these animals. Some of these unique challenges of transporting non-human primates, include the impact of public perception of non-human primates as cargo, maintaining biosecurity of non-human primate cargo, safety of both the non-human primate and public contacts, meeting the vital husbandry needs of varying species of non-human primates and compliance with numerous regulatory agencies, which may have overlapping responsibilities. This discussion will focus on these important considerations, as they relate to the legal international transportation of non-human primates for scientific use.

Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

Energy Technology Data Exchange (ETDEWEB)

Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver [Robert Koch-Institut, Berlin (Germany); Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D. [Paul-Ehrlich-Institut, Langen (Germany); Bannert, Norbert; Kurth, Reinhard [Robert Koch-Institut, Berlin (Germany); Norley, Stephen, E-mail: NorleyS@rki.de [Robert Koch-Institut, Berlin (Germany)

2016-02-15

Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

International Nuclear Information System (INIS)

Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver; Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D.; Bannert, Norbert; Kurth, Reinhard; Norley, Stephen

2016-01-01

Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

Recombinant human parainfluenza virus type 2 with mutations in V that permit cellular interferon signaling are not attenuated in non-human primates

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Schaap-Nutt, Anne; D’Angelo, Christopher; Amaro-Carambot, Emerito; Nolan, Sheila M.; Davis, Stephanie; Wise, Shenelle-Marie; Higgins, Caraline; Bradley, Konrad; Kim, Olivia; Mayor, Reina; Skiadopoulos, Mario H.; Collins, Peter L.; Murphy, Brian R.; Schmidt, Alexander C.

2010-01-01

The HPIV2 V protein inhibits type I interferon (IFN) induction and signaling. To manipulate the V protein, whose coding sequence overlaps that of the polymerase-associated phosphoprotein (P), without altering the P protein, we generated an HPIV2 virus in which P and V are expressed from separate genes (rHPIV2-P+V). rHPIV2-P+V replicated like HPIV2-WT in vitro and in non-human primates. HPIV2-P+V was modified by introducing two separate mutations into the V protein to create rHPIV2-L101E/L102E and rHPIV2-Δ122–127. In contrast to HPIV2-WT, both mutant viruses were unable to degrade STAT2, leaving virus-infected cells susceptible to IFN. Neither mutant, nor HPIV2-WT, induced significant amounts of IFN-β in infected cells. Surprisingly, neither rHPIV2-L101E/L102E nor rHPIV2-Δ122–127 was attenuated in two species of non-human primates. This indicates that loss of HPIV2's ability to inhibit IFN signaling is insufficient to attenuate virus replication in vivo as long as IFN induction is still inhibited. PMID:20667570

Recent advances in primate nutritional ecology.

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Righini, Nicoletta

2017-04-01

Nutritional ecology seeks to explain, in an ecological and evolutionary context, how individuals choose, acquire, and process food to satisfy their nutritional requirements. Historically, studies of primate feeding ecology have focused on characterizing diets in terms of the botanical composition of the plants consumed. Further, dietary studies have demonstrated how patch and food choice in relation to time spent foraging and feeding are influenced by the spatial and temporal distribution of resources and by social factors such as feeding competition, dominance, or partner preferences. From a nutritional perspective, several theories including energy and protein-to-fiber maximization, nutrient mixing, and toxin avoidance, have been proposed to explain the food choices of non-human primates. However, more recently, analytical frameworks such as nutritional geometry have been incorporated into primatology to explore, using a multivariate approach, the synergistic effects of multiple nutrients, secondary metabolites, and energy requirements on primate food choice. Dietary strategies associated with nutrient balancing highlight the tradeoffs that primates face in bypassing or selecting particular feeding sites and food items. In this Special Issue, the authors bring together a set of studies focusing on the nutritional ecology of a diverse set of primate taxa characterized by marked differences in dietary emphasis. The authors present, compare, and discuss the diversity of strategies used by primates in diet selection, and how species differences in ecology, physiology, anatomy, and phylogeny can affect patterns of nutrient choice and nutrient balancing. The use of a nutritionally explicit analytical framework is fundamental to identify the nutritional requirements of different individuals of a given species, and through its application, direct conservation efforts can be applied to regenerate and protect specific foods and food patches that offer the opportunity of a

76 FR 13120 - Requirements for Importers of Nonhuman Primates

Science.gov (United States)

2011-03-10

... Requirements for Importers of Nonhuman Primates AGENCY: Centers for Disease Control and Prevention (CDC... primates (NHPs). Written comments were to be received on or before March 7, 2011. We have received a... regulations (42 CFR 71.53) for the imporation of live nonhuman primates (NHPs) by extending existing...

Domain- and nucleotide-specific Rev response element regulation of feline immunodeficiency virus production

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Na, Hong; Huisman, Willem; Ellestad, Kristofor K.; Phillips, Tom R.; Power, Christopher

2010-01-01

Computational analysis of feline immunodeficiency virus (FIV) RNA sequences indicated that common FIV strains contain a rev response element (RRE) defined by a long unbranched hairpin with 6 stem-loop sub-domains, termed stem-loop A (SLA). To examine the role of the RNA secondary structure of the RRE, mutational analyses were performed in both an infectious FIV molecular clone and a FIV CAT-RRE reporter system. These studies disclosed that the stems within SLA (SA1, 2, 3, 4, and 5) of the RRE were critical but SA6 was not essential for FIV replication and CAT expression. These studies also revealed that the secondary structure rather than an antisense protein (ASP) mediates virus expression and replication in vitro. In addition, a single synonymous mutation within the FIV-RRE, SA3/45, reduced viral reverse transcriptase activity and p24 expression after transfection but in addition also showed a marked reduction in viral expression and production following infection. PMID:20570310

Male germline stem cells in non-human primates

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S. Sharma

2017-09-01

Full Text Available Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs. These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent species; therefore the findings from rodent models cannot be extrapolated to primates. Due to limited availability of human embryonic and testicular samples for research purposes, two non-human primate models (marmoset and macaque monkeys are extensively employed to understand human germline development and differentiation. This review provides a broader introduction to the in vivo and in vitro germline stem cell terminology from primordial to differentiating germ cells. Primordial germ cells (PGCs are the most immature germ cells colonizing the gonad prior to sex differentiation into testes or ovaries. PGC specification and migratory patterns among different primate species are compared in the review. It also reports the distinctions and similarities in expression patterns of pluripotency markers (OCT4A, NANOG, SALL4 and LIN28 during embryonic developmental stages, among marmosets, macaques and humans. This review presents a comparative summary with immunohistochemical and molecular evidence of germ cell marker expression patterns during postnatal developmental stages, among humans and non-human primates. Furthermore, it reports findings from the recent literature investigating the plasticity behavior of germ cells and stem cells in other organs of humans and monkeys. The use of non-human primate models would enable bridging the knowledge gap in primate GSC research and understanding the mechanisms involved in germline development. Reported similarities in regulatory mechanisms and germ cell expression profile in primates demonstrate the preclinical significance of monkey models for development of

Reproductive/developmental toxicity and immunotoxicity assessment in the nonhuman primate model

International Nuclear Information System (INIS)

Buse, Eberhard; Habermann, Gunnar; Osterburg, Ingrid; Korte, Rainhart; Weinbauer, Gerhard F.

2003-01-01

Nonhuman primates are being used increasingly as a non-rodent animal model during preclinical toxicology and safety assessment on the basis of proven similarity and comparability between nonhuman primates and humans. The validity of the nonhuman primate models applies to many aspects of toxicological testing and holds particularly true for the evaluation of reproductive toxicology and developmental toxicology. More recently, the advent of humanized antibodies and vaccines imposed further demand on nonhuman primate models since many immunotherapeutics do not interact with rodent receptors but frequently only cross-react with primate tissue. In this paper we discuss the suitability of primate models for reproductive, developmental and immunotoxicology testing, and present our initial data on the development of lymphatic organs and immune system in a nonhuman primate model

Cancers related to immunodeficiencies : Update and perspectives

NARCIS (Netherlands)

Mortaz, Esmaeil; Tabarsi, Payam; Mansouri, Davod; Khosravi, Adnan; Garssen, Johan; Velayati, Aliakbar; Adcock, Ian M.

2016-01-01

The life span of patients with primary and secondary immunodeficiency is increasing due to recent improvements in therapeutic strategies. While the incidence of primary immunodeficiencies (PIDs) is 1:10,000 births, that of secondary immunodeficiencies are more common and are associated with

Primates' Socio-Cognitive Abilities: What Kind of Comparisons Makes Sense?

Science.gov (United States)

Byrnit, Jill T

2015-09-01

Referential gestures are of pivotal importance to the human species. We effortlessly make use of each others' referential gestures to attend to the same things, and our ability to use these gestures show themselves from very early in life. Almost 20 years ago, James Anderson and colleagues presented an experimental paradigm with which to examine the use of referential gestures in non-human primates: the object-choice task. Since then, numerous object-choice studies have been made, not only with primates but also with a range of other animal taxa. Surprisingly, several non-primate species appear to perform better in the object-choice task than primates do. Different hypotheses have been offered to explain the results. Some of these have employed generalizations about primates or subsets of primate taxa that do not take into account the unparalleled diversity that exists between species within the primate order on parameters relevant to the requirements of the object-choice task, such as social structure, feeding ecology, and general morphology. To examine whether these broad primate generalizations offer a fruitful organizing framework within which to interpret the results, a review was made of all published primate results on the use of gazing and glancing cues with species ordered along the primate phylogenetic tree. It was concluded that differences between species may be larger than differences between ancestry taxa, and it is suggested that we need to start rethinking why we are testing animals on experimental paradigms that do not take into account what are the challenges of their natural habitat.

Diversity, habitat preferences, and conservation of the primates of Southern Assam, India: The story of a primate paradise

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Muhammed Khairujjaman Mazumder

2014-12-01

Full Text Available The southern part of Assam in India, a part of the Indo-Burma Biodiversity hotspot, harbors a myriad number of wild plant and animal species. Although there is only one protected area, the Barail Wildlife Sanctuary (Cachar district and a few reserve forests (RFs, there are as many as eight primates inhabiting the region – a diversity hardly found elsewhere. In addition to the protected area and RFs, tea gardens and secondary forests also serve as habitats for animals. The border areas of the region with the states of Manipur, Mizoram, Meghalaya, and Tripura are among the most important abodes of these primates. Unfortunately, these primates are under constant threat from multiple sources. The present article provides an extensive survey of the available literature on the primates of southern Assam with reference to their distribution, habitat preferences, threats, and conservation. Additionally, data from field observations of the author are also presented.

The ORF59 DNA polymerase processivity factor homologs of Old World primate RV2 rhadinoviruses are highly conserved nuclear antigens expressed in differentiated epithelium in infected macaques

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Burnside Kellie L

2009-11-01

Full Text Available Abstract Background ORF59 DNA polymerase processivity factor of the human rhadinovirus, Kaposi's sarcoma-associated herpesvirus (KSHV, is required for efficient copying of the genome during virus replication. KSHV ORF59 is antigenic in the infected host and is used as a marker for virus activation and replication. Results We cloned, sequenced and expressed the genes encoding related ORF59 proteins from the RV1 rhadinovirus homologs of KSHV from chimpanzee (PtrRV1 and three species of macaques (RFHVMm, RFHVMn and RFHVMf, and have compared them with ORF59 proteins obtained from members of the more distantly-related RV2 rhadinovirus lineage infecting the same non-human primate species (PtrRV2, RRV, MneRV2, and MfaRV2, respectively. We found that ORF59 homologs of the RV1 and RV2 Old World primate rhadinoviruses are highly conserved with distinct phylogenetic clustering of the two rhadinovirus lineages. RV1 and RV2 ORF59 C-terminal domains exhibit a strong lineage-specific conservation. Rabbit antiserum was developed against a C-terminal polypeptide that is highly conserved between the macaque RV2 ORF59 sequences. This anti-serum showed strong reactivity towards ORF59 encoded by the macaque RV2 rhadinoviruses, RRV (rhesus and MneRV2 (pig-tail, with no cross reaction to human or macaque RV1 ORF59 proteins. Using this antiserum and RT-qPCR, we determined that RRV ORF59 is expressed early after permissive infection of both rhesus primary fetal fibroblasts and African green monkey kidney epithelial cells (Vero in vitro. RRV- and MneRV2-infected foci showed strong nuclear expression of ORF59 that correlated with production of infectious progeny virus. Immunohistochemical studies of an MneRV2-infected macaque revealed strong nuclear expression of ORF59 in infected cells within the differentiating layer of epidermis corroborating previous observations that differentiated epithelial cells are permissive for replication of KSHV-like rhadinoviruses

The evolution of primate general and cultural intelligence.

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Reader, Simon M; Hager, Yfke; Laland, Kevin N

2011-04-12

There are consistent individual differences in human intelligence, attributable to a single 'general intelligence' factor, g. The evolutionary basis of g and its links to social learning and culture remain controversial. Conflicting hypotheses regard primate cognition as divided into specialized, independently evolving modules versus a single general process. To assess how processes underlying culture relate to one another and other cognitive capacities, we compiled ecologically relevant cognitive measures from multiple domains, namely reported incidences of behavioural innovation, social learning, tool use, extractive foraging and tactical deception, in 62 primate species. All exhibited strong positive associations in principal component and factor analyses, after statistically controlling for multiple potential confounds. This highly correlated composite of cognitive traits suggests social, technical and ecological abilities have coevolved in primates, indicative of an across-species general intelligence that includes elements of cultural intelligence. Our composite species-level measure of general intelligence, 'primate g(S)', covaried with both brain volume and captive learning performance measures. Our findings question the independence of cognitive traits and do not support 'massive modularity' in primate cognition, nor an exclusively social model of primate intelligence. High general intelligence has independently evolved at least four times, with convergent evolution in capuchins, baboons, macaques and great apes.

The well-being of laboratory non-human primates.

Science.gov (United States)

Baker, Kate C; Dettmer, Amanda M

2017-01-01

The well-being of non-human primates in captivity is of joint concern to scientists, veterinarians, colony managers, caretakers, and researchers working with non-human primates in biomedical research. With increased regulatory, accreditation, and research focus on optimizing the use of social housing for laboratory primates, as well as the advent of techniques to assess indices of chronic stress and related measures of well-being, there is no better time to present the most current advances in the field of non-human primate behavioral management. The collective body of research presented here was inspired in part by a 2014 symposium entitled, "Chronic Hormones and Demographic Variables: Center-Wide Studies on Non-Human Primate Well-Being" held at the American Society of Primatologists' 37th Annual Meeting in Decatur, GA. By aiming to target readership with scientific and/or management oversight of captive primate behavioral management programs, this special issue provides badly-needed guidance for implementing social housing programs in a research environment and leverages collaboration across multiple facilities to address key components of behavioral management, explore refinements in how well-being can be measured, and identify the interrelationships between varying indices. Am. J. Primatol. 79:e22520, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Why is a landscape perspective important in studies of primates?

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Arroyo-Rodríguez, Víctor; Fahrig, Lenore

2014-10-01

With accelerated deforestation and fragmentation through the tropics, assessing the impact that landscape spatial changes may have on biodiversity is paramount, as this information is required to design and implement effective management and conservation plans. Primates are expected to be particularly dependent on the landscape context; yet, our understanding on this topic is limited as the majority of primate studies are at the local scale, meaning that landscape-scale inferences are not possible. To encourage primatologists to assess the impact of landscape changes on primates, and help future studies on the topic, we describe the meaning of a "landscape perspective" and evaluate important assumptions of using such a methodological approach. We also summarize a number of important, but unanswered, questions that can be addressed using a landscape-scale study design. For example, it is still unclear if habitat loss has larger consistent negative effects on primates than habitat fragmentation per se. Furthermore, interaction effects between habitat area and other landscape effects (e.g., fragmentation) are unknown for primates. We also do not know if primates are affected by synergistic interactions among factors at the landscape scale (e.g., habitat loss and diseases, habitat loss and climate change, hunting, and land-use change), or whether landscape complexity (or landscape heterogeneity) is important for primate conservation. Testing for patterns in the responses of primates to landscape change will facilitate the development of new guidelines and principles for improving primate conservation. © 2014 Wiley Periodicals, Inc.

Glycosylphosphatidylinositol-anchored CD4 supports human immunodeficiency virus type 1 replication, but not cytopathic effect, in T-cell transfectants.

OpenAIRE

Marshall, W L; Mittler, E S; Avery, P; Lawrence, J P; Finberg, R W

1994-01-01

Despite equivalent p24 antigen production, HSB-2 T cells expressing glycosylphosphatidylinositol (GPi)-linked CD4 were productively infected without cell death or syncytium formation, unlike HSB-2 transfectants expressing wild-type CD4 (wtCD4). HSB-2 transfectants dually expressing wtCD4 and GPi-linked CD4 formed syncytia and died. Thus, wtCD4 expression is critical for human immunodeficiency virus cytopathic effect in HSB-2 transfectants.

Effect of low-dose gamma radiation on HIV replication in human peripheral blood mononuclear cells

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Xu, Y. [British Columbia Centre for Excellence in HIV/AIDS, British Columbia (Canada); Conway, B. [British Columbia Centre for Excellence in HIV/AIDS, British Columbia (Canada)]|[British Columbia Centre for Excellence in HIV/AIDS, British Columbia (Canada). Dept. of Medicine; Montaner, J.S.G. [British Columbia Centre for Excellence in HIV/AIDS, British Columbia (Canada)]|[British Columbia Centre for Excellence in HIV/AIDS, British Columbia (Canada). Dept. of Medicine]|[Canadian HIV Trials Network, Vancouver (Canada); O`Shaughnessy, M.V. [British Columbia Centre for Excellence in HIV/AIDS, British Columbia (Canada)]|[British Columbia Centre for Excellence in HIV/AIDS, British Columbia (Canada). Faculty of Medicine]|[Canadian HIV Trials Network, Vancouver (Canada); Greenstock, C.L. [AECL Research, Chalk River, Ontario (Canada). Radiation Biology and Health Physics Branch

1996-08-01

Recent studies have demonstrated that UV light and x-irradiation enhance human immunodeficiency virus (HIV) gene expression. There are few published data on related effects of {gamma}-radiation. This may be of clinical relevance, as radiotherapy has been used extensively for the treatment of acquired immunodeficiency syndrome associated conditions. We have studied the effects of {gamma}-radiation on HIV replication in mono-nuclear cells (MC). These cells were obtained from five seronegative healthy donors, exposed to 0-200 cGy {gamma}-radiation, stimulated with phytohemagglutinin-P (PHA-P) for 24 h, infected with a laboratory strain of HIV (HTLV-IIIB, multiplicity of infection = 0.001), then carried in culture for 14 days. Overall, when considering p24 antigen levels on days 7 and 11 in cultures established from cells exposed to 50 cGy, the maximal levels were significantly higher than those measured in the parallel control cultures taken as a whole (P < 0.05), with viral replication enhanced as much as 1000-fold in one case. No significant cytotoxicity was observed following exposure to doses up to 50 cGy. The mechanism of the observed effect remains unknown but may relate to direct gene activation and/or free radical generation, leading to such activation. To date, there is no evidence that viral stimulation occurs following therapeutic radiation in a clinical setting. (author).

Effect of low-dose gamma radiation on HIV replication in human peripheral blood mononuclear cells

International Nuclear Information System (INIS)

Xu, Y.; Conway, B.; O'Shaughnessy, M.V.; Greenstock, C.L.

1996-01-01

Recent studies have demonstrated that UV light and x-irradiation enhance human immunodeficiency virus (HIV) gene expression. There are few published data on related effects of γ-radiation. This may be of clinical relevance, as radiotherapy has been used extensively for the treatment of acquired immunodeficiency syndrome associated conditions. We have studied the effects of γ-radiation on HIV replication in mono-nuclear cells (MC). These cells were obtained from five seronegative healthy donors, exposed to 0-200 cGy γ-radiation, stimulated with phytohemagglutinin-P (PHA-P) for 24 h, infected with a laboratory strain of HIV (HTLV-IIIB, multiplicity of infection = 0.001), then carried in culture for 14 days. Overall, when considering p24 antigen levels on days 7 and 11 in cultures established from cells exposed to 50 cGy, the maximal levels were significantly higher than those measured in the parallel control cultures taken as a whole (P < 0.05), with viral replication enhanced as much as 1000-fold in one case. No significant cytotoxicity was observed following exposure to doses up to 50 cGy. The mechanism of the observed effect remains unknown but may relate to direct gene activation and/or free radical generation, leading to such activation. To date, there is no evidence that viral stimulation occurs following therapeutic radiation in a clinical setting. (author)

Pandemic Swine-Origin H1N1 Influenza Virus Replicates to Higher Levels and Induces More Fever and Acute Inflammatory Cytokines in Cynomolgus versus Rhesus Monkeys and Can Replicate in Common Marmosets.

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Petra Mooij

Full Text Available The close immunological and physiological resemblance with humans makes non-human primates a valuable model for studying influenza virus pathogenesis and immunity and vaccine efficacy against infection. Although both cynomolgus and rhesus macaques are frequently used in influenza virus research, a direct comparison of susceptibility to infection and disease has not yet been performed. In the current study a head-to-head comparison was made between these species, by using a recently described swine-origin pandemic H1N1 strain, A/Mexico/InDRE4487/2009. In comparison to rhesus macaques, cynomolgus macaques developed significantly higher levels of virus replication in the upper airways and in the lungs, involving both peak level and duration of virus production, as well as higher increases in body temperature. In contrast, clinical symptoms, including respiratory distress, were more easily observed in rhesus macaques. Expression of sialyl-α-2,6-Gal saccharides, the main receptor for human influenza A viruses, was 50 to 73 times more abundant in trachea and bronchus of cynomolgus macaques relative to rhesus macaques. The study also shows that common marmosets, a New World non-human primate species, are susceptible to infection with pandemic H1N1. The study results favor the cynomolgus macaque as model for pandemic H1N1 influenza virus research because of the more uniform and high levels of virus replication, as well as temperature increases, which may be due to a more abundant expression of the main human influenza virus receptor in the trachea and bronchi.

Three-dimensional primate molar enamel thickness.

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Olejniczak, Anthony J; Tafforeau, Paul; Feeney, Robin N M; Martin, Lawrence B

2008-02-01

Molar enamel thickness has played an important role in the taxonomic, phylogenetic, and dietary assessments of fossil primate teeth for nearly 90 years. Despite the frequency with which enamel thickness is discussed in paleoanthropological discourse, methods used to attain information about enamel thickness are destructive and record information from only a single plane of section. Such semidestructive planar methods limit sample sizes and ignore dimensional data that may be culled from the entire length of a tooth. In light of recently developed techniques to investigate enamel thickness in 3D and the frequent use of enamel thickness in dietary and phylogenetic interpretations of living and fossil primates, the study presented here aims to produce and make available to other researchers a database of 3D enamel thickness measurements of primate molars (n=182 molars). The 3D enamel thickness measurements reported here generally agree with 2D studies. Hominoids show a broad range of relative enamel thicknesses, and cercopithecoids have relatively thicker enamel than ceboids, which in turn have relatively thicker enamel than strepsirrhine primates, on average. Past studies performed using 2D sections appear to have accurately diagnosed the 3D relative enamel thickness condition in great apes and humans: Gorilla has the relatively thinnest enamel, Pan has relatively thinner enamel than Pongo, and Homo has the relatively thickest enamel. Although the data set presented here has some taxonomic gaps, it may serve as a useful reference for researchers investigating enamel thickness in fossil taxa and studies of primate gnathic biology.

Occurrence and distribution of Indian primates

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Karanth, K.K.; Nichols, J.D.; Hines, J.E.

2010-01-01

Global and regional species conservation efforts are hindered by poor distribution data and range maps. Many Indian primates face extinction, but assessments of population status are hindered by lack of reliable distribution data. We estimated the current occurrence and distribution of 15 Indian primates by applying occupancy models to field data from a country-wide survey of local experts. We modeled species occurrence in relation to ecological and social covariates (protected areas, landscape characteristics, and human influences), which we believe are critical to determining species occurrence in India. We found evidence that protected areas positively influence occurrence of seven species and for some species are their only refuge. We found evergreen forests to be more critical for some primates along with temperate and deciduous forests. Elevation negatively influenced occurrence of three species. Lower human population density was positively associated with occurrence of five species, and higher cultural tolerance was positively associated with occurrence of three species. We find that 11 primates occupy less than 15% of the total land area of India. Vulnerable primates with restricted ranges are Golden langur, Arunachal macaque, Pig-tailed macaque, stump-tailed macaque, Phayre's leaf monkey, Nilgiri langur and Lion-tailed macaque. Only Hanuman langur and rhesus macaque are widely distributed. We find occupancy modeling to be useful in determining species ranges, and in agreement with current species ranking and IUCN status. In landscapes where monitoring efforts require optimizing cost, effort and time, we used ecological and social covariates to reliably estimate species occurrence and focus species conservation efforts. ?? Elsevier Ltd.

Phalangeal morphology of Shanghuang fossil primates.

Science.gov (United States)

Gebo, Daniel L; Dagosto, Marian; Ni, Xijun; Beard, K Christopher

2017-12-01

Here, we describe hundreds of isolated phalanges attributed to middle Eocene fossil primates from the Shanghuang fissure-fillings from southern Jiangsu Province, China. Extending knowledge based on previous descriptions of postcranial material from Shanghuang, this sample of primate finger and toe bones includes proximal phalanges, middle phalanges, and over three hundred nail-bearing distal phalanges. Most of the isolated proximal and middle phalanges fall within the range of small-bodied individuals, suggesting an allocation to the smaller haplorhine primates identified at Shanghuang, including eosimiids. In contrast to the proximal and middle phalanges from Shanghuang, there are a variety of shapes, sizes, and possible taxonomic allocations for the distal phalanges. Two distal phalangeal morphologies are numerically predominant at Shanghuang. The sample of larger bodied specimens is best allocated to the medium-sized adapiform Adapoides while the smaller ones are allocated to eosimiids on the basis of the commonality of dental and tarsal remains of these taxa at Shanghuang. The digit morphology of Adapoides is similar morphologically to that of notharctines and cercamoniines, while eosimiid digit morphology is unlike living anthropoids. Other primate distal phalangeal morphologies at Shanghuang include grooming "claws" as well as specimens attributable to tarsiids, tarsiiforms, the genus Macrotarsius, and a variety of adapiforms. One group of distal phalanges at Shanghuang is morphologically indistinguishable from those of living anthropoids. All of the phalanges suggest long fingers and toes for the fossil primates of Shanghaung, and their digit morphology implies arboreality with well-developed digital flexion and strong, grasping hands and feet. Copyright © 2017 Elsevier Ltd. All rights reserved.

Primates on display: Potential disease consequences beyond bushmeat.

Science.gov (United States)

Muehlenbein, Michael P

2017-01-01

Human interactions with nonhuman primates vary tremendously, from daily cultural engagements and food commodities, to pet ownership and tourist encounters. These interactions provide opportunities for the exchange of pathogenic organisms (both zoonoses and anthroponoses). As exposures are not limited to areas where bushmeat usage continues to be a major problem, we must work to understand better our motivations for engaging in activities like owning primates as pets and having direct physical contact with wild primates within the context of nature-based tourism. These topics, and the theoretical potential for pathogen transmission, are reviewed in the present manuscript. This is followed by a case study utilizing 3845 survey responses collected from four international locations known for primate-based tourism, with results indicating that while a majority of people understand that they can give/get diseases to/from wild primates, a surprising percentage would still touch or feed these animals if given the opportunity. Many people still choose to touch and/or own primates, as their drive to bond with animals outweighs some basic health behaviors. Desires to tame, control, or otherwise establish emotional connections with other species, combined with the central role of touch for exploring our environment, necessitate the development of better communication and educational campaigns to minimize risks of emerging infectious diseases. © 2017 American Association of Physical Anthropologists.

Screening for simian foamy virus infection by using a combined antigen Western blot assay: evidence for a wide distribution among Old World primates and identification of four new divergent viruses

International Nuclear Information System (INIS)

Hussain, Althaf I.; Shanmugam, Vedapuri; Bhullar, Vinod B.; Beer, Brigitte E.; Vallet, Dominique; Gautier-Hion, Annie; Wolfe, Nathan D.; Karesh, William B.; Kilbourn, Annelisa M.; Tooze, Zeena; Heneine, Walid; Switzer, William M.

2003-01-01

Simian foamy viruses (SFVs) belong to a genetically and antigenically diverse class of retroviruses that naturally infect a wide range of nonhuman primates (NHPs) and can also be transmitted to humans occupationally exposed to NHPs. Current serologic detection of SFV infection requires separate Western blot (WB) testing by using two different SFV antigens [SFV AGM (African green monkey) and SFV CPZ (chimpanzee)]. However, this method is labor intensive and validation is limited to only small numbers of NHPs. To facilitate serologic SFV testing, we developed a WB assay that combines antigens from both SFV AGM and SFV CPZ . The combined-antigen WB (CA-WB) assay was validated with 145 serum samples from 129 NHPs (32 African and Asian species) and 16 humans, all with known SFV infection status determined by PCR. Concordant CA-WB results were obtained for all 145 PCR-positive or -negative primate and human specimens, giving the assay a 100% sensitivity and specificity. In addition, no reactivity was observed in sera from persons positive for human immunodeficiency virus or human T cell lymphotropic virus (HIV/HTLV) (n = 25) or HIV/HTLV-negative U.S. blood donors (n = 100). Using the CA-WB assay, we screened 360 sera from 43 Old World primate species and found an SFV prevalence of about 68% in both African and Asian primates. We also isolated SFV from the blood of four seropositive primates (Allenopithecus nigroviridis, Trachypithecus francoisi, Hylobates pileatus, and H. leucogenys) not previously known to be infected with SFV. Phylogenetic analysis of integrase sequences from these isolates confirmed that all four SFVs represent new, distinct, and highly divergent lineages. These results demonstrate the ability of the CA-WB assay to detect infection in a large number of NHP species, including previously uncharacterized infections with divergent SFVs

Human immunodeficiency virus long terminal repeat responds to T-cell activation signals

International Nuclear Information System (INIS)

Tong-Starksen, S.E.; Luciw, P.A.; Peterlin, B.M.

1987-01-01

Human immunodeficiency virus (HIV), the causative agent of AIDS, infects and kills lymphoid cells bearing the CD4 antigen. In an infected cell, a number of cellular as well as HIV-encoded gene products determine the levels of viral gene expression and HIV replication. Efficient HIV replication occurs in activated T cells. Utilizing transient expression assays, the authors show that gene expression directed by the HIV long terminal repeat (LTR) increases in response to T-cell activation signals. The effects of T-cell activation and of the HIV-encoded trans-activator (TAT) are multiplicative. Analysis of mutations and deletions in the HIV LTR reveals that the region responding to T-cell activation signals is located at positions -105 to -80. These sequences are composed of two direct repeats, which are homologous to the core transcriptional enhancer elements in the simian virus 40 genome. The studies reveal that these elements function as the HIV enhancer. By acting directly on the HIV LTR, T-cell activation may play an important role in HIV gene expression and in the activation of latent HIV

New STLV-3 strains and a divergent SIVmus strain identified in non-human primate bushmeat in Gabon

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Liégeois Florian

2012-03-01

Full Text Available Abstract Background Human retroviral infections such as Human Immunodeficiency Virus (HIV or Human T-cell Lymphotropic Virus (HTLV are the result of simian zoonotic transmissions through handling and butchering of Non-Human Primates (NHP or by close contact with pet animals. Recent studies on retroviral infections in NHP bushmeat allowed for the identification of numerous Simian Immunodeficiency Viruses (SIV and Simian T-cell Lymphotropic Viruses (STLV to which humans are exposed. Nevertheless, today, data on simian retroviruses at the primate/hunter interface remain scarce. We conducted a pilot study on 63 blood and/or tissues samples derived from NHP bushmeat seized by the competent authorities in different locations across the country. Results SIV and STLV were detected by antibodies to HIV and HTLV antigens, and PCRs were performed on samples with an HIV or/and HTLV-like or indeterminate profile. Fourteen percent of the samples cross-reacted with HIV antigens and 44% with HTLV antigens. We reported STLV-1 infections in five of the seven species tested. STLV-3 infections, including a new STLV-3 subtype, STLV-1 and -3 co-infections, and triple SIV, STLV-1, STLV-3 infections were observed in red-capped mangabeys (C.torquatus. We confirmed SIV infections by PCR and sequence analyses in mandrills, red-capped mangabeys and showed that mustached monkeys in Gabon are infected with a new SIV strain basal to the SIVgsn/mus/mon lineage that did not fall into the previously described SIVmus lineages reported from the corresponding species in Cameroon. The same monkey (subspecies can thus be carrier of, at least, three distinct SIVs. Overall, the minimal prevalence observed for both STLV and SIV natural infections were 26.9% and 11.1% respectively. Conclusions Overall, these data, obtained from a restricted sampling, highlight the need for further studies on simian retroviruses in sub-Saharan Africa to better understand their evolutionary history and to

Impaired human immunodeficiency virus type 1 replicative fitness in atypical viremic non-progressor individuals

Czech Academy of Sciences Publication Activity Database

Weber, Jan; Gibson, R. M.; Sácká, Lenka; Strunin, Dmytro; Hodek, Jan; Weberová, Jitka; Pávová, Marcela; Alouani, D. J.; Asaad, R.; Rodriguez, B.; Lederman, M. M.; Quinones-Mateu, M. E.

2017-01-01

Roč. 14, Mar 20 (2017), č. článku 15. ISSN 1742-6405 R&D Projects: GA MŠk(CZ) LK11207 Institutional support: RVO:61388963 Keywords : HIV -1 * replicative fitness * disease progression * viremic non-progressors Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 1.605, year: 2016 https://aidsrestherapy.biomedcentral.com/articles/10.1186/s12981-017-0144-0

On folivory, competition, and intelligence: generalisms, overgeneralizations, and models of primate evolution.

Science.gov (United States)

Sayers, Ken

2013-04-01

Considerations of primate behavioral evolution often proceed by assuming the ecological and competitive milieus of particular taxa via their relative exploitation of gross food types, such as fruits versus leaves. Although this "fruit/leaf dichotomy" has been repeatedly criticized, it continues to be implicitly invoked in discussions of primate socioecology and female social relationships and is explicitly invoked in models of brain evolution. An expanding literature suggests that such views have severely limited our knowledge of the social and ecological complexities of primate folivory. This paper examines the behavior of primate folivore-frugivores, with particular emphasis on gray langurs (traditionally, Semnopithecus entellus) within the broader context of evolutionary ecology. Although possessing morphological characteristics that have been associated with folivory and constrained activity patterns, gray langurs are known for remarkable plasticity in ecology and behavior. Their diets are generally quite broad and can be discussed in relation to Liem's Paradox, the odd coupling of anatomical feeding specializations with a generalist foraging strategy. Gray langurs, not coincidentally, inhabit arguably the widest range of habitats for a nonhuman primate, including high elevations in the Himalayas. They provide an excellent focal point for examining the assumptions and predictions of behavioral, socioecological, and cognitive evolutionary models. Contrary to the classical descriptions of the primate folivore, Himalayan and other gray langurs-and, in actuality, many leaf-eating primates-range widely, engage in resource competition (both of which have previously been noted for primate folivores), and solve ecological problems rivaling those of more frugivorous primates (which has rarely been argued for primate folivores). It is maintained that questions of primate folivore adaptation, temperate primate adaptation, and primate evolution more generally cannot be

Using non-human primates to benefit humans: research and organ transplantation.

Science.gov (United States)

Shaw, David; Dondorp, Wybo; de Wert, Guido

2014-11-01

Emerging biotechnology may soon allow the creation of genetically human organs inside animals, with non-human primates (henceforth simply "primates") and pigs being the best candidate species. This prospect raises the question of whether creating organs in primates in order to then transplant them into humans would be more (or less) acceptable than using them for research. In this paper, we examine the validity of the purported moral distinction between primates and other animals, and analyze the ethical acceptability of using primates to create organs for human use.

Postcopulatory sexual selection influences baculum evolution in primates and carnivores.

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Brindle, Matilda; Opie, Christopher

2016-12-14

The extreme morphological variability of the baculum across mammals is thought to be the result of sexual selection (particularly, high levels of postcopulatory selection). However, the evolutionary trajectory of the mammalian baculum is little studied and evidence for the adaptive function of the baculum has so far been elusive. Here, we use Markov chain Monte Carlo methods implemented in a Bayesian phylogenetic framework to reconstruct baculum evolution across the mammalian class and investigate the rate of baculum length evolution within the primate order. We then test the effects of testes mass (postcopulatory sexual selection), polygamy, seasonal breeding and intromission duration on the baculum in primates and carnivores. The ancestral mammal did not have a baculum, but both ancestral primates and carnivores did. No relationship was found between testes mass and baculum length in either primates or carnivores. Intromission duration correlated with baculum presence over the course of primate evolution, and prolonged intromission predicts significantly longer bacula in extant primates and carnivores. Both polygamous and seasonal breeding systems predict significantly longer bacula in primates. These results suggest the baculum plays an important role in facilitating reproductive strategies in populations with high levels of postcopulatory sexual selection. © 2016 The Authors.

Primates and the Evolution of Long-Slow Life Histories

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Jones, James Holland

2011-01-01

Summary Primates are characterized by relatively late ages at first reproduction, long lives and low fertility. Together, these traits define a life-history of reduced reproductive effort. Understanding the optimal allocation of reproductive effort, and specifically reduced reproductive effort, has been one of the key problems motivating the development of life history theory. Because of their unusual constellation of life-history traits, primates play an important role in the continued development of life history theory. In this review, I present the evidence for the reduced reproductive effort life histories of primates and discuss the ways that such life-history tactics are understood in contemporary theory. Such tactics are particularly consistent with the predictions of stochastic demographic models, suggesting a key role for environmental variability in the evolution of primate life histories. The tendency for primates to specialize in high-quality, high-variability food items may make them particularly susceptible to environmental variability and explain their low reproductive-effort tactics. I discuss recent applications of life history theory to human evolution and emphasize the continuity between models used to explain peculiarities of human reproduction and senescence with the long, slow life histories of primates more generally. PMID:21959161

Cooperation and deception in primates.

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Hall, Katie; Brosnan, Sarah F

2017-08-01

Though competition and cooperation are often considered opposing forces in an arms race driving natural selection, many animals, including humans, cooperate in order to mitigate competition with others. Understanding others' psychological states, such as seeing and knowing, others' goals and intentions, and coordinating actions are all important for complex cooperation-as well as for predicting behavior in order to take advantage of others through tactical deception, a form of competition. We outline evidence of primates' understanding of how others perceive the world, and then consider how the evidence from both deception and cooperation fits this framework to give us a more complete understanding of the evolution of complex social cognition in primates. In experimental food competitions, primates flexibly manipulate group-mates' behavior to tactically deceive them. Deception can infiltrate cooperative interactions, such as when one takes an unfair share of meat after a coordinated hunt. In order to counter competition of this sort, primates maintain cooperation through partner choice, partner control, and third party punishment. Yet humans appear to stand alone in their ability to understand others' beliefs, which allows us not only to deceive others with the explicit intent to create a false belief, but it also allows us to put ourselves in others' shoes to determine when cheaters need to be punished, even if we are not directly disadvantaged by the cheater. Copyright © 2016 Elsevier Inc. All rights reserved.

Inhibition of human immunodeficiency virus replication by a dual CCR5/CXCR4 antagonist

DEFF Research Database (Denmark)

Princen, Katrien; Hatse, Sigrid; Vermeire, Kurt

2004-01-01

Here we report that the N-pyridinylmethyl cyclam analog AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2 (50% inhibitory concentration [IC(50)] ranging from 1.2 to 26.5 microM) in various T-cell lines, CCR5...... at the virus entry stage. AMD3451 dose-dependently inhibited the intracellular Ca(2+) signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca(2+) flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells. The compound did...... not interfere with chemokine-induced Ca(2+) signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca(2+) signaling by itself at concentrations up to 400 microM. In freshly isolated monocytes, AMD3451 inhibited the Ca(2+) flux induced by CXCL12 and CCL4...

Oldest known euarchontan tarsals and affinities of Paleocene Purgatorius to Primates.

Science.gov (United States)

Chester, Stephen G B; Bloch, Jonathan I; Boyer, Doug M; Clemens, William A

2015-02-03

Earliest Paleocene Purgatorius often is regarded as the geologically oldest primate, but it has been known only from fossilized dentitions since it was first described half a century ago. The dentition of Purgatorius is more primitive than those of all known living and fossil primates, leading some researchers to suggest that it lies near the ancestry of all other primates; however, others have questioned its affinities to primates or even to placental mammals. Here we report the first (to our knowledge) nondental remains (tarsal bones) attributed to Purgatorius from the same earliest Paleocene deposits that have yielded numerous fossil dentitions of this poorly known mammal. Three independent phylogenetic analyses that incorporate new data from these fossils support primate affinities of Purgatorius among euarchontan mammals (primates, treeshrews, and colugos). Astragali and calcanei attributed to Purgatorius indicate a mobile ankle typical of arboreal euarchontan mammals generally and of Paleocene and Eocene plesiadapiforms specifically and provide the earliest fossil evidence of arboreality in primates and other euarchontan mammals. Postcranial specializations for arboreality in the earliest primates likely played a key role in the evolutionary success of this mammalian radiation in the Paleocene.

Cancers related to Immunodeficiencies:Update and perspectives

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Esmaeil Mortaz

2016-09-01

Full Text Available The life span of patients with primary and secondary immunodeficiency is increasing due to recent improvements in therapeutic strategies. Whilst, the incidence of primary immunodeficiencies (PIDs is 1:10.000 births, that of secondary immunodeficiencies is more common and are associated with post transplantation immune dysfunction or with immunosuppressive medication for human immunodeficiency virus (HIV or with human T-cell lymphotropic virus (HTLV infection.After infection, malignancy is the most prevalent cause of death in both children and adults with primary immunodeficiency disorders (PIDs. PIDs more often associated with cancer include common variable immunodeficiency (CVID, Wiskott Aldrich syndrome (WAS, ataxia-telangiectasia (AT and severe combined immunodeficiency (SCID. This suggests that a protective immune response against both infectious non-self (pathogens and malignant self-challenges (cancer exist. The increased incidence of cancer has been attributed to defective elimination of altered or transformed cells and/or defective immunity towards cancer cells. The concept of abberant immune surveillance occurring in PIDs is supported by evidence in mice and from patients undergoing immunosuppression after transplantation. Here, we discuss the importance of PID defects in the development of malignancies, the current limitations associated with molecular pathogenesis of these diseases and emphasize the need for further knowledge of how specific mutations can modulate the immune system to alter immunosurveillance and thereby play a key role in the etiology of malignancies in PID patients.

Vaccination with Gag, Vif, and Nef gene fragments affords partial control of viral replication after mucosal challenge with SIVmac239.

Science.gov (United States)

Martins, Mauricio A; Wilson, Nancy A; Piaskowski, Shari M; Weisgrau, Kim L; Furlott, Jessica R; Bonaldo, Myrna C; Veloso de Santana, Marlon G; Rudersdorf, Richard A; Rakasz, Eva G; Keating, Karen D; Chiuchiolo, Maria J; Piatak, Michael; Allison, David B; Parks, Christopher L; Galler, Ricardo; Lifson, Jeffrey D; Watkins, David I

2014-07-01

Broadly targeted cellular immune responses are thought to be important for controlling replication of human and simian immunodeficiency viruses (HIV and SIV). However, eliciting such responses by vaccination is complicated by immunodominance, the preferential targeting of only a few of the many possible epitopes of a given antigen. This phenomenon may be due to the coexpression of dominant and subdominant epitopes by the same antigen-presenting cell and may be overcome by distributing these sequences among several different vaccine constructs. Accordingly, we tested whether vaccinating rhesus macaques with "minigenes" encoding fragments of Gag, Vif, and Nef resulted in broadened cellular responses capable of controlling SIV replication. We delivered these minigenes through combinations of recombinant Mycobacterium bovis BCG (rBCG), electroporated recombinant DNA (rDNA) along with an interleukin-12 (IL-12)-expressing plasmid (EP rDNA plus pIL-12), yellow fever vaccine virus 17D (rYF17D), and recombinant adenovirus serotype 5 (rAd5). Although priming with EP rDNA plus pIL-12 increased the breadth of vaccine-induced T-cell responses, this effect was likely due to the improved antigen delivery afforded by electroporation rather than modulation of immunodominance. Indeed, Mamu-A*01(+) vaccinees mounted CD8(+) T cells directed against only one subdominant epitope, regardless of the vaccination regimen. After challenge with SIVmac239, vaccine efficacy was limited to a modest reduction in set point in some of the groups and did not correlate with standard T-cell measurements. These findings suggest that broad T-cell responses elicited by conventional vectors may not be sufficient to substantially contain AIDS virus replication. Immunodominance poses a major obstacle to the generation of broadly targeted, HIV-specific cellular responses by vaccination. Here we attempted to circumvent this phenomenon and thereby broaden the repertoire of SIV-specific cellular responses by

Primate beta oscillations and rhythmic behaviors.

Science.gov (United States)

Merchant, Hugo; Bartolo, Ramón

2018-03-01

The study of non-human primates in complex behaviors such as rhythm perception and entrainment is critical to understand the neurophysiological basis of human cognition. Next to reviewing the role of beta oscillations in human beat perception, here we discuss the role of primate putaminal oscillatory activity in the control of rhythmic movements that are guided by a sensory metronome or internally gated. The analysis of the local field potentials of the behaving macaques showed that gamma-oscillations reflect local computations associated with stimulus processing of the metronome, whereas beta-activity involves the entrainment of large putaminal circuits, probably in conjunction with other elements of cortico-basal ganglia-thalamo-cortical circuit, during internally driven rhythmic tapping. Thus, this review emphasizes the need of parametric neurophysiological observations in non-human primates that display a well-controlled behavior during high-level cognitive processes.

A biochemical defect in the repair of alkylated DNA in cells from an immunodeficient patient (46BR)

International Nuclear Information System (INIS)

Teo, I.A.; Broughton, B.C.; Day, R.S.; James, M.R.; Karran, P.; Mayne, L.V.; Lehmann, A.R.

1983-01-01

The fibroblast cell strain 46BR, derived from an immunodeficient individual, is hypersensitive to the lethal effects of a variety of DNA-damaging agents, this effect being particularly marked for monofunctional methylating agents. After U.V. irradiation 46BR cells show normal unscheduled DNA synthesis, daughter strand repair, and recovery of DNA and RNA synthesis. The inhibition of DNA replicative synthesis by U.V. is slightly less than that of normal cells. After gamma-irradiation the rejoining of strand breaks is normal as are the kinetics of replicative DNA synthesis. Following treatment with dimethylsulphate, replicative DNA synthesis is affected in a similar way to normal cells, unscheduled DNA synthesis may be increased relative to normal cells, but more strand breaks persist in 46BR than in normal cells. In addition 46BR cells are hypersensitive to the toxic effects of 3-aminobenzamide, an inhibitor of ADP-ribosyl transferase. This enzyme is involved in the ligation step of repair of alkylation damage. A hypothesis is presented suggesting that 46BR may be defective in DNA ligase I

Molecular evolution of the primate antiviral restriction factor tetherin.

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Jun Liu

Full Text Available BACKGROUND: Tetherin is a recently identified antiviral restriction factor that restricts HIV-1 particle release in the absence of the HIV-1 viral protein U (Vpu. It is reminiscent of APOBEC3G and TRIM5a that also antagonize HIV. APOBEC3G and TRIM5a have been demonstrated to evolve under pervasive positive selection throughout primate evolution, supporting the red-queen hypothesis. Therefore, one naturally presumes that Tetherin also evolves under pervasive positive selection throughout primate evolution and supports the red-queen hypothesis. Here, we performed a detailed evolutionary analysis to address this presumption. METHODOLOGY/PRINCIPAL FINDINGS: Results of non-synonymous and synonymous substitution rates reveal that Tetherin as a whole experiences neutral evolution rather than pervasive positive selection throughout primate evolution, as well as in non-primate mammal evolution. Sliding-window analyses show that the regions of the primate Tetherin that interact with viral proteins are under positive selection or relaxed purifying selection. In particular, the sites identified under positive selection generally focus on these regions, indicating that the main selective pressure acting on the primate Tetherin comes from virus infection. The branch-site model detected positive selection acting on the ancestral branch of the New World Monkey lineage, suggesting an episodic adaptive evolution. The positive selection was also found in duplicated Tetherins in ruminants. Moreover, there is no bias in the alterations of amino acids in the evolution of the primate Tetherin, implying that the primate Tetherin may retain broad spectrum of antiviral activity by maintaining structure stability. CONCLUSIONS/SIGNIFICANCE: These results conclude that the molecular evolution of Tetherin may be attributed to the host-virus arms race, supporting the Red Queen hypothesis, and Tetherin may be in an intermediate stage in transition from neutral to pervasive

Nonhuman primate models of focal cerebral ischemia

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Jingjing Fan

2017-01-01

Full Text Available Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

Colombian and Peruvian Primate Censusing Studies,

Science.gov (United States)

1975-06-01

34PG ’AMR 0719) from the Pan American Health Organization (PAHO) and funds from the Instituto de Desarrollo de los Recursos Naturales Renovables...04 FEB. 7?5 En Iia. " Discusion de la cirta convenio para el Desorrolla do un Proyocto do investi-&iciones Piologicas solbre Primates no humanos onl...adecuadas para garantizar la utilizacion y la pe.-petuidad de especies de primates no humanos . 2- Realizar investigaciones de campo para determinar: el estado

Primate-specific evolution of an LDLR enhancer

Energy Technology Data Exchange (ETDEWEB)

Wang, Qian-Fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles; Eisen, Michael B.; Cheng, Jan-Fang; Rubin,Edward M.; Boffelli, Dario

2005-12-01

Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. In this study we identified an anthropoid primate-specific sequence element that contributed to the regulatory evolution of the low-density lipoprotein receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we found that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates. Our study demonstrates one molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions in the primate lineage leading to human.

Approach to a child with primary immunodeficiency

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Özge Yılmaz

2010-09-01

Full Text Available Primary immunodeficiencies are clinically and epidemiologically important, despite their low prevalence, due to the associated risk of high morbidity and mortality. Most commonly encountered primary immunodeficiencies include humoral immune system deficiencies, cellular immune system defects, combined immunodeficiencies, phagocyte system defects, complement system defects. Classical clinical findings of immunodeficiencies include recurrent, severe infections which do not respond to treatment or which progress with complications as well as tendency to develop infections with low virulence microorganisms. Moreover, they may present with autoimmunity, autoinflammatory or hemaphagocytic syndromes. Congenital diseases usually start in early childhood and lead to morbidity and mortality. Therefore, early diagnosis may be life saving and allow increasing quality of life, genetic counseling or prenatal diagnosis. Considering primary immunodeficiencies more frequently in differential diagnosis and early immunological evaluation would lead to early diagnosis of these patients and allow them to reach early treatment or preventive measures.

Transgene Expression and Host Cell Responses to Replication-Defective, Single-Cycle, and Replication-Competent Adenovirus Vectors

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Catherine M. Crosby

2017-02-01

immunodeficient mice, SC-Ad drove stronger luciferase expression than RC- or RD-Ad. These data demonstrate better transgene expression by SC- and RC-Ad in vitro and in vivo than RD-Ad. This higher expression by the replicating vectors results in a peak of expression within 1 to 2 days followed by cell death of infected cells and release of transgene products. While SC- and RC-Ad expression were similar in mice and in Syrian hamsters, RC-Ad provoked much stronger ISG induction which may explain in part SC-Ad′s ability to generate stronger and more persistent immune responses than RC-Ad in Ad permissive hamsters.

Human Immunodeficiency Viruses Appear Compartmentalized to the Female Genital Tract in Cross-Sectional Analyses but Genital Lineages Do Not Persist Over Time

OpenAIRE

Bull, Marta E.; Heath, Laura M.; McKernan-Mullin, Jennifer L.; Kraft, Kelli M.; Acevedo, Luis; Hitti, Jane E.; Cohn, Susan E.; Tapia, Kenneth A.; Holte, Sarah E.; Dragavon, Joan A.; Coombs, Robert W.; Mullins, James I.; Frenkel, Lisa M.

2013-01-01

Background. Whether unique human immunodeficiency type 1 (HIV) genotypes occur in the genital tract is important for vaccine development and management of drug resistant viruses. Multiple cross-sectional studies suggest HIV is compartmentalized within the female genital tract. We hypothesize that bursts of HIV replication and/or proliferation of infected cells captured in cross-sectional analyses drive compartmentalization but over time genital-specific viral lineages do not form; rather viru...

Novel host restriction factors implicated in HIV-1 replication.

Science.gov (United States)

Ghimire, Dibya; Rai, Madhu; Gaur, Ritu

2018-04-01

Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host cellular proteins during its replication in the target cell. While many of these host cellular proteins facilitate viral replication, a number of them are reported to inhibit HIV-1 replication at various stages of its life cycle. These host cellular proteins, which are known as restriction factors, constitute an integral part of the host's first line of defence against the viral pathogen. Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an HIV-1 restriction factor, several human proteins have been identified that exhibit anti-HIV-1 restriction. While each restriction factor employs a distinct mechanism of inhibition, the HIV-1 virus has equally evolved complex counter strategies to neutralize their inhibitory effect. APOBEC3G, tetherin, sterile alpha motif and histidine-aspartate domain 1 (SAMHD1), and trim-5α are some of the best known HIV-1 restriction factors that have been studied in great detail. Recently, six novel restriction factors were discovered that exhibit significant antiviral activity: endoplasmic reticulum α1,2-mannosidase I (ERManI), translocator protein (TSPO), guanylate-binding protein 5 (GBP5), serine incorporator (SERINC3/5) and zinc-finger antiviral protein (ZAP). The focus of this review is to discuss the antiviral mechanism of action of these six restriction factors and provide insights into the probable counter-evasion strategies employed by the HIV-1 virus. The recent discovery of new restriction factors substantiates the complex host-pathogen interactions occurring during HIV-1 pathogenesis and makes it imperative that further investigations are conducted to elucidate the molecular basis of HIV-1 replication.

Adaptive evolution of facial colour patterns in Neotropical primates

OpenAIRE

Santana, Sharlene E.; Lynch Alfaro, Jessica; Alfaro, Michael E.

2012-01-01

The rich diversity of primate faces has interested naturalists for over a century. Researchers have long proposed that social behaviours have shaped the evolution of primate facial diversity. However, the primate face constitutes a unique structure where the diverse and potentially competing functions of communication, ecology and physiology intersect, and the major determinants of facial diversity remain poorly understood. Here, we provide the first evidence for an adaptive role of facial co...

The skin in primary immunodeficiency disorders

NARCIS (Netherlands)

Sillevis Smitt, J. Henk; Wulffraat, Nico M.; Kuijpers, Taco W.

2005-01-01

Primary immunodeficiency disorders comprise serious and rare diseases, predominantly in children. The skin may be involved in a primary immunodeficiency and the cutaneous alterations such as infections, eczematous dermatitis, erythroderma, autoimmune dermatoses and vasculitis may be the basis for

Comparative Triceps Surae Morphology in Primates: A Review

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Jandy B. Hanna

2011-01-01

Full Text Available Primate locomotor evolution, particularly the evolution of bipedalism, is often examined through morphological studies. Many of these studies have examined the uniqueness of the primate forelimb, and others have examined the primate hip and thigh. Few data exist, however, regarding the myology and function of the leg muscles, even though the ankle plantar flexors are highly important during human bipedalism. In this paper, we draw together data on the fiber type and muscle mass variation in the ankle plantar flexors of primates and make comparisons to other mammals. The data suggest that great apes, atelines, and lorisines exhibit similarity in the mass distribution of the triceps surae. We conclude that variation in triceps surae may be related to the shared locomotor mode exhibited by these groups and that triceps surae morphology, which approaches that of humans, may be related to frequent use of semiplantigrade locomotion and vertical climbing.

Primates as Predictors of Mammal Community Diversity in the Forest Ecosystems of Madagascar

Science.gov (United States)

Muldoon, Kathleen M.; Goodman, Steven M.

2015-01-01

The geographic distribution of species is the typical metric for identifying priority areas for conservation. Since most biodiversity remains poorly studied, a subset of charismatic species, such as primates, often stand as surrogates for total biodiversity. A central question is therefore, how effectively do primates predict the pooled species richness of other mammalian taxa? We used lemurs as indicator species to predict total non-primate mammal community richness in the forest ecosystems of Madagascar. We combine environmental and species occurrence data to ascertain the extent to which primate diversity can predict (1) non-primate mammal α-diversity (species richness), (2) non-primate complementarity, and (3) non-primate β-diversity (species turnover). Our results indicate that primates are effective predictors of non-primate mammal community diversity in the forest ecosystems of Madagascar after controlling for habitat. When individual orders of mammals are considered, lemurs effectively predict the species richness of carnivorans and rodents (but not afrosoricids), complementarity of rodents (but not carnivorans or afrosoricids), and all individual components of β-diversity. We conclude that lemurs effectively predict total non-primate community richness. However, surrogate species alone cannot achieve complete representation of biodiversity. PMID:26334525

A comparative psychophysical approach to visual perception in primates.

Science.gov (United States)

Matsuno, Toyomi; Fujita, Kazuo

2009-04-01

Studies on the visual processing of primates, which have well developed visual systems, provide essential information about the perceptual bases of their higher-order cognitive abilities. Although the mechanisms underlying visual processing are largely shared between human and nonhuman primates, differences have also been reported. In this article, we review psychophysical investigations comparing the basic visual processing that operates in human and nonhuman species, and discuss the future contributions potentially deriving from such comparative psychophysical approaches to primate minds.

Meeting report: Spontaneous lesions and diseases in wild, captive-bred, and zoo-housed nonhuman primates and in nonhuman primate species used in drug safety studies.

Science.gov (United States)

Sasseville, V G; Mansfield, K G; Mankowski, J L; Tremblay, C; Terio, K A; Mätz-Rensing, K; Gruber-Dujardin, E; Delaney, M A; Schmidt, L D; Liu, D; Markovits, J E; Owston, M; Harbison, C; Shanmukhappa, S; Miller, A D; Kaliyaperumal, S; Assaf, B T; Kattenhorn, L; Macri, S Cummings; Simmons, H A; Baldessari, A; Sharma, P; Courtney, C; Bradley, A; Cline, J M; Reindel, J F; Hutto, D L; Montali, R J; Lowenstine, L J

2012-11-01

The combination of loss of habitat, human population encroachment, and increased demand of select nonhuman primates for biomedical research has significantly affected populations. There remains a need for knowledge and expertise in understanding background findings as related to the age, source, strain, and disease status of nonhuman primates. In particular, for safety/biomedical studies, a broader understanding and documentation of lesions would help clarify background from drug-related findings. A workshop and a minisymposium on spontaneous lesions and diseases in nonhuman primates were sponsored by the concurrent Annual Meetings of the American College of Veterinary Pathologists and the American Society for Veterinary Clinical Pathology held December 3-4, 2011, in Nashville, Tennessee. The first session had presentations from Drs Lowenstine and Montali, pathologists with extensive experience in wild and zoo populations of nonhuman primates, which was followed by presentations of 20 unique case reports of rare or newly observed spontaneous lesions in nonhuman primates (see online files for access to digital whole-slide images corresponding to each case report at http://www.scanscope.com/ACVP%20Slide%20Seminars/2011/Primate%20Pathology/view.apml). The minisymposium was composed of 5 nonhuman-primate researchers (Drs Bradley, Cline, Sasseville, Miller, Hutto) who concentrated on background and spontaneous lesions in nonhuman primates used in drug safety studies. Cynomolgus and rhesus macaques were emphasized, with some material presented on common marmosets. Congenital, acquired, inflammatory, and neoplastic changes were highlighed with a focus on clinical, macroscopic, and histopathologic findings that could confound the interpretation of drug safety studies.

The behavioral genetics of nonhuman primates: Status and prospects.

Science.gov (United States)

Rogers, Jeffrey

2018-01-01

The complexity and diversity of primate behavior have long attracted the attention of ethologists, psychologists, behavioral ecologists, and neuroscientists. Recent studies have advanced our understanding of the nature of genetic influences on differences in behavior among individuals within species. A number of analyses have focused on the genetic analysis of behavioral reactions to specific experimental tests, providing estimates of the degree of genetic control over reactivity, and beginning to identify the genes involved. Substantial progress is also being made in identifying genetic factors that influence the structure and function of the primate brain. Most of the published studies on these topics have examined either cercopithecines or chimpanzees, though a few studies have addressed these questions in other primate species. One potentially important line of research is beginning to identify the epigenetic processes that influence primate behavior, thus revealing specific cellular and molecular mechanisms by which environmental experiences can influence gene expression or gene function relevant to behavior. This review summarizes many of these studies of non-human primate behavioral genetics. The primary focus is on analyses that address the nature of the genes and genetic processes that affect differences in behavior among individuals within non-human primate species. Analyses of between species differences and potential avenues for future research are also discussed. © 2018 American Association of Physical Anthropologists.

Replacement of Murine Leukemia Virus Readthrough Mechanism by Human Immunodeficiency Virus Frameshift Allows Synthesis of Viral Proteins and Virus Replication

Science.gov (United States)

Brunelle, Marie-Noëlle; Brakier-Gingras, Léa; Lemay, Guy

2003-01-01

Retroviruses use unusual recoding strategies to synthesize the Gag-Pol polyprotein precursor of viral enzymes. In human immunodeficiency virus, ribosomes translating full-length viral RNA can shift back by 1 nucleotide at a specific site defined by the presence of both a slippery sequence and a downstream stimulatory element made of an extensive secondary structure. This so-called frameshift mechanism could become a target for the development of novel antiviral strategies. A different recoding strategy is used by other retroviruses, such as murine leukemia viruses, to synthesize the Gag-Pol precursor; in this case, a stop codon is suppressed in a readthrough process, again due to the presence of a specific structure adopted by the mRNA. Development of antiframeshift agents will greatly benefit from the availability of a simple animal and virus model. For this purpose, the murine leukemia virus readthrough region was rendered inactive by mutagenesis and the frameshift region of human immunodeficiency virus was inserted to generate a chimeric provirus. This substitution of readthrough by frameshift allows the synthesis of viral proteins, and the chimeric provirus sequence was found to generate infectious viruses. This system could be a most interesting alternative to study ribosomal frameshift in the context of a virus amenable to the use of a simple animal model. PMID:12584361

Immune protection of nonhuman primates against Ebola virus with single low-dose adenovirus vectors encoding modified GPs.

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Nancy J Sullivan

2006-06-01

Full Text Available Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd encoding the Ebola glycoprotein (GP and nucleoprotein (NP has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine.To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 10(10 particles, two logs lower than that used previously.Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 10(10 rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate.

Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs

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Geisbert, Joan B; Shedlock, Devon J; Xu, Ling; Lamoreaux, Laurie; Custers, Jerome H. H. V; Popernack, Paul M; Yang, Zhi-Yong; Pau, Maria G; Roederer, Mario; Koup, Richard A; Goudsmit, Jaap; Jahrling, Peter B; Nabel, Gary J

2006-01-01

Background Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine. Methods and Findings To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 1010 particles, two logs lower than that used previously. Conclusions Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 1010 rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate. PMID:16683867

High level of surface CD4 prevents stable human immunodeficiency virus infection of T-cell transfectants.

OpenAIRE

Marshall, W L; Diamond, D C; Kowalski, M M; Finberg, R W

1992-01-01

CD4 is the principal receptor for the human immunodeficiency virus (HIV). We have isolated and studied CD4-expressing tumor cell clones made by expressing CD4 in the T-cell tumor line HSB. Two clones, one designated HSBCD4, a clone expressing low levels of CD4, and the other, HSB10xCD4, a high-expresser CD4+ clone, were studied for their ability to bind and replicate HIV. In contrast to many other CD4+ cells that down-modulate CD4 following HIV infection, the HSB10xCD4 clones continued to exp...

The ecology of primate material culture.

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Koops, Kathelijne; Visalberghi, Elisabetta; van Schaik, Carel P

2014-11-01

Tool use in extant primates may inform our understanding of the conditions that favoured the expansion of hominin technology and material culture. The 'method of exclusion' has, arguably, confirmed the presence of culture in wild animal populations by excluding ecological and genetic explanations for geographical variation in behaviour. However, this method neglects ecological influences on culture, which, ironically, may be critical for understanding technology and thus material culture. We review all the current evidence for the role of ecology in shaping material culture in three habitual tool-using non-human primates: chimpanzees, orangutans and capuchin monkeys. We show that environmental opportunity, rather than necessity, is the main driver. We argue that a better understanding of primate technology requires explicit investigation of the role of ecological conditions. We propose a model in which three sets of factors, namely environment, sociality and cognition, influence invention, transmission and retention of material culture. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Human Immunodeficiency Virus Playing Hide-and-Seek: Understanding the TFH Cell Reservoir and Proposing Strategies to Overcome the Follicle Sanctuary

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Yew Ann Leong

2017-05-01

Full Text Available Human immunodeficiency virus (HIV infects millions of people worldwide, and new cases continue to emerge. Once infected, the virus cannot be cleared by the immune system and causes acquired immunodeficiency syndrome. Combination antiretroviral therapeutic regimen effectively suppresses viral replication and halts disease progression. The treatment, however, does not eliminate the virus-infected cells, and interruption of treatment inevitably leads to viral rebound. The rebound virus originates from a group of virus-infected cells referred to as the cellular reservoir of HIV. Identifying and eliminating the HIV reservoir will prevent viral rebound and cure HIV infection. In this review, we focus on a recently discovered HIV reservoir in a subset of CD4+ T cells called the follicular helper T (TFH cells. We describe the potential mechanisms for the emergence of reservoir in TFH cells, and the strategies to target and eliminate this viral reservoir.

Conservation of myeloid surface antigens on primate granulocytes.

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Letvin, N L; Todd, R F; Palley, L S; Schlossman, S F; Griffin, J D

1983-02-01

Monoclonal antibodies reactive with myeloid cell surface antigens were used to study evolutionary changes in granulocyte surface antigens from primate species. Certain of these granulocyte membrane antigens are conserved in phylogenetically distant species, indicating the potential functional importance of these structures. The degree of conservation of these antigens reflects the phylogenetic relationship between primate species. Furthermore, species of the same genus show similar patterns of binding to this panel of anti-human myeloid antibodies. This finding of conserved granulocyte surface antigens suggests that non-human primates may provide a model system for exploring uses of monoclonal antibodies in the treatment of human myeloid disorders.

Exceptionally long 5' UTR short tandem repeats specifically linked to primates.

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Namdar-Aligoodarzi, P; Mohammadparast, S; Zaker-Kandjani, B; Talebi Kakroodi, S; Jafari Vesiehsari, M; Ohadi, M

2015-09-10

We have previously reported genome-scale short tandem repeats (STRs) in the core promoter interval (i.e. -120 to +1 to the transcription start site) of protein-coding genes that have evolved identically in primates vs. non-primates. Those STRs may function as evolutionary switch codes for primate speciation. In the current study, we used the Ensembl database to analyze the 5' untranslated region (5' UTR) between +1 and +60 of the transcription start site of the entire human protein-coding genes annotated in the GeneCards database, in order to identify "exceptionally long" STRs (≥5-repeats), which may be of selective/adaptive advantage. The importance of this critical interval is its function as core promoter, and its effect on transcription and translation. In order to minimize ascertainment bias, we analyzed the evolutionary status of the human 5' UTR STRs of ≥5-repeats in several species encompassing six major orders and superorders across mammals, including primates, rodents, Scandentia, Laurasiatheria, Afrotheria, and Xenarthra. We introduce primate-specific STRs, and STRs which have expanded from mouse to primates. Identical co-occurrence of the identified STRs of rare average frequency between 0.006 and 0.0001 in primates supports a role for those motifs in processes that diverged primates from other mammals, such as neuronal differentiation (e.g. APOD and FGF4), and craniofacial development (e.g. FILIP1L). A number of the identified STRs of ≥5-repeats may be human-specific (e.g. ZMYM3 and DAZAP1). Future work is warranted to examine the importance of the listed genes in primate/human evolution, development, and disease. Copyright © 2015 Elsevier B.V. All rights reserved.

The comparative anatomy of the forelimb veins of primates.

OpenAIRE

Thiranagama, R; Chamberlain, A T; Wood, B A

1989-01-01

One hundred and thirteen forelimbs taken from 62 individuals belonging to 17 primate genera were dissected to reveal the entire course of the superficial venous system. The course of the deep venous system was also documented in at least one forelimb of each primate genus, and the number and location of perforating veins was recorded in 18 human and 45 non-human primate limbs. In Pan, Gorilla and in about 25% of human specimens the lateral superficial vein was confined to the forearm, while i...

Nonhuman Primate Studies to Advance Vision Science and Prevent Blindness.

Science.gov (United States)

Mustari, Michael J

2017-12-01

Most primate behavior is dependent on high acuity vision. Optimal visual performance in primates depends heavily upon frontally placed eyes, retinal specializations, and binocular vision. To see an object clearly its image must be placed on or near the fovea of each eye. The oculomotor system is responsible for maintaining precise eye alignment during fixation and generating eye movements to track moving targets. The visual system of nonhuman primates has a similar anatomical organization and functional capability to that of humans. This allows results obtained in nonhuman primates to be applied to humans. The visual and oculomotor systems of primates are immature at birth and sensitive to the quality of binocular visual and eye movement experience during the first months of life. Disruption of postnatal experience can lead to problems in eye alignment (strabismus), amblyopia, unsteady gaze (nystagmus), and defective eye movements. Recent studies in nonhuman primates have begun to discover the neural mechanisms associated with these conditions. In addition, genetic defects that target the retina can lead to blindness. A variety of approaches including gene therapy, stem cell treatment, neuroprosthetics, and optogenetics are currently being used to restore function associated with retinal diseases. Nonhuman primates often provide the best animal model for advancing fundamental knowledge and developing new treatments and cures for blinding diseases. © The Author(s) 2017. Published by Oxford University Press on behalf of the National Academy of Sciences. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus

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Sparger, E. E.; Pitt, K. A.

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs. PMID:28384338

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus.

Directory of Open Access Journals (Sweden)

C D Eckstrand

Full Text Available Feline immunodeficiency virus (FIV infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN, and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC-associated viral RNA (vRNA by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus.

Science.gov (United States)

Eckstrand, C D; Sparger, E E; Pitt, K A; Murphy, B G

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.

Interferon-alpha mediates restriction of human immunodeficiency virus type-1 replication in primary human macrophages at an early stage of replication.

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Kelly M Cheney

2010-10-01

Full Text Available Type I interferons (IFNα and β are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα.

Why Primates? The Importance of Nonhuman Primates for Understanding Human Infancy

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Weiss, Daniel J.; Santos, Laurie R.

2006-01-01

We introduce the thematic collection by noting some striking similarities in the cognitive abilities of human infants and nonhuman primates. What are the implications of these similarities for our comprehension of human infant cognition? After providing a brief historical and conceptual background on comparative behavioral research, we discuss how…

Autoimmunity and primary immunodeficiency: two sides of the same coin?

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Schmidt, Reinhold E; Grimbacher, Bodo; Witte, Torsten

2017-12-19

Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions; however, increased understanding of the complex immune regulatory and signalling mechanisms involved, coupled with the application of genetic analysis, is revealing the complex relationships between primary immunodeficiency syndromes and autoimmune diseases. Single-gene defects can cause rare diseases that predominantly present with autoimmune symptoms. Such genetic defects also predispose individuals to recurrent infections (a hallmark of immunodeficiency) and can cause primary immunodeficiencies, which can also lead to immune dysregulation and autoimmunity. Moreover, risk factors for polygenic rheumatic diseases often exist in the same genes as the mutations that give rise to primary immunodeficiency syndromes. In this Review, various primary immunodeficiency syndromes are presented, along with their pathogenetic mechanisms and relationship to autoimmune diseases, in an effort to increase awareness of immunodeficiencies that occur concurrently with autoimmune diseases and to highlight the need to initiate appropriate genetic tests. The growing knowledge of various genetically determined pathologic mechanisms in patients with immunodeficiencies who have autoimmune symptoms opens up new avenues for personalized molecular therapies that could potentially treat immunodeficiency and autoimmunity at the same time, and that could be further explored in the context of autoimmune rheumatic diseases.

9 CFR 3.87 - Primary enclosures used to transport nonhuman primates.

Science.gov (United States)

2010-01-01

... nonhuman primates. 3.87 Section 3.87 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., and Transportation of Nonhuman Primates 2 Transportation Standards § 3.87 Primary enclosures used to transport nonhuman primates. Any person subject to the Animal Welfare regulations (9 CFR parts 1, 2, and 3...

Primate Anatomy, Kinematics, and Principles for Humanoid Design

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Ambrose, Robert O.; Ambrose, Catherine G.

2004-01-01

The primate order of animals is investigated for clues in the design of Humanoid Robots. The pursuit is directed with a theory that kinematics, musculature, perception, and cognition can be optimized for specific tasks by varying the proportions of limbs, and in particular, the points of branching in kinematic trees such as the primate skeleton. Called the Bifurcated Chain Hypothesis, the theory is that the branching proportions found in humans may be superior to other animals and primates for the tasks of dexterous manipulation and other human specialties. The primate taxa are defined, contemporary primate evolution hypotheses are critiqued, and variations within the order are noted. The kinematic branching points of the torso, limbs and fingers are studied for differences in proportions across the order, and associated with family and genus capabilities and behaviors. The human configuration of a long waist, long neck, and short arms is graded using a kinematic workspace analysis and a set of design axioms for mobile manipulation robots. It scores well. The re emergence of the human waist, seen in early Prosimians and Monkeys for arboreal balance, but lost in the terrestrial Pongidae, is postulated as benefiting human dexterity. The human combination of an articulated waist and neck will be shown to enable the use of smaller arms, achieving greater regions of workspace dexterity than the larger limbs of Gorillas and other Hominoidea.

Personality, social hierarchy and hormones in primates

OpenAIRE

KONEČNÁ, Martina

2010-01-01

This thesis deals with two main issues: personality (stable individual differences in behavior) and behavioral endocrinology (or socioendocrinology) in nonhuman primates. The first part of the thesis comprises of two primate personality studies of two species: Hanuman langurs and Barbary macaques. Two basic methods of animal personality research (behavioral coding and trait rating) were compared. Stability of personality assessments has been demonstrated. Social rank of individuals was used t...

Nutritional ecology of entomophagy in humans and other primates.

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Raubenheimer, David; Rothman, Jessica M

2013-01-01

Entomophagy is widespread among nonhuman primates and is common among many human communities. However, the extent and patterns of entomophagy vary substantially both in humans and nonhuman primates. Here we synthesize the literature to examine why humans and other primates eat insects and what accounts for the variation in the extent to which they do so. Variation in the availability of insects is clearly important, but less understood is the role of nutrients in entomophagy. We apply a multidimensional analytical approach, the right-angled mixture triangle, to published data on the macronutrient compositions of insects to address this. Results showed that insects eaten by humans spanned a wide range of protein-to-fat ratios but were generally nutrient dense, whereas insects with high protein-to-fat ratios were eaten by nonhuman primates. Although suggestive, our survey exposes a need for additional, standardized, data.

Interactions between social structure, demography, and transmission determine disease persistence in primates.

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Ryan, Sadie J; Jones, James H; Dobson, Andrew P

2013-01-01

Catastrophic declines in African great ape populations due to disease outbreaks have been reported in recent years, yet we rarely hear of similar disease impacts for the more solitary Asian great apes, or for smaller primates. We used an age-structured model of different primate social systems to illustrate that interactions between social structure and demography create 'dynamic constraints' on the pathogens that can establish and persist in primate host species with different social systems. We showed that this varies by disease transmission mode. Sexually transmitted infections (STIs) require high rates of transmissibility to persist within a primate population. In particular, for a unimale social system, STIs require extremely high rates of transmissibility for persistence, and remain at extremely low prevalence in small primates, but this is less constrained in longer-lived, larger-bodied primates. In contrast, aerosol transmitted infections (ATIs) spread and persist at high prevalence in medium and large primates with moderate transmissibility;, establishment and persistence in small-bodied primates require higher relative rates of transmissibility. Intragroup contact structure - the social network - creates different constraints for different transmission modes, and our model underscores the importance of intragroup contacts on infection prior to intergroup movement in a structured population. When alpha males dominate sexual encounters, the resulting disease transmission dynamics differ from when social interactions are dominated by mother-infant grooming events, for example. This has important repercussions for pathogen spread across populations. Our framework reveals essential social and demographic characteristics of primates that predispose them to different disease risks that will be important for disease management and conservation planning for protected primate populations.

First comparative study of primate morphological and molecular evolutionary rates including muscle data: implications for the tempo and mode of primate and human evolution

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Diogo, Rui; Peng, Zuogang; Wood, Bernard

2013-01-01

Here we provide the first report about the rates of muscle evolution derived from Bayesian and parsimony cladistic analyses of primate higher-level phylogeny, and compare these rates with published rates of molecular evolution. It is commonly accepted that there is a ‘general molecular slow-down of hominoids’, but interestingly the rates of muscle evolution in the nodes leading and within the hominoid clade are higher than those in the vast majority of other primate clades. The rate of muscle evolution at the node leading to Homo (1.77) is higher than that at the nodes leading to Pan (0.89) and particularly to Gorilla (0.28). Notably, the rates of muscle evolution at the major euarchontan and primate nodes are different, but within each major primate clade (Strepsirrhini, Platyrrhini, Cercopithecidae and Hominoidea) the rates at the various nodes, and particularly at the nodes leading to the higher groups (i.e. including more than one genera), are strikingly similar. We explore the implications of these new data for the tempo and mode of primate and human evolution. PMID:23320764

Remarkable ancient divergences amongst neglected lorisiform primates

Science.gov (United States)

Nekaris, K. Anne‐Isola; Perkin, Andrew; Bearder, Simon K.; Pimley, Elizabeth R.; Schulze, Helga; Streicher, Ulrike; Nadler, Tilo; Kitchener, Andrew; Zischler, Hans; Zinner, Dietmar; Roos, Christian

2015-01-01

Lorisiform primates (Primates: Strepsirrhini: Lorisiformes) represent almost 10% of the living primate species and are widely distributed in sub‐Saharan Africa and South/South‐East Asia; however, their taxonomy, evolutionary history, and biogeography are still poorly understood. In this study we report the largest molecular phylogeny in terms of the number of represented taxa. We sequenced the complete mitochondrial cytochrome b gene for 86 lorisiform specimens, including ∼80% of all the species currently recognized. Our results support the monophyly of the Galagidae, but a common ancestry of the Lorisinae and Perodicticinae (family Lorisidae) was not recovered. These three lineages have early origins, with the Galagidae and the Lorisinae diverging in the Oligocene at about 30 Mya and the Perodicticinae emerging in the early Miocene. Our mitochondrial phylogeny agrees with recent studies based on nuclear data, and supports Euoticus as the oldest galagid lineage and the polyphyletic status of Galagoides. Moreover, we have elucidated phylogenetic relationships for several species never included before in a molecular phylogeny. The results obtained in this study suggest that lorisiform diversity remains substantially underestimated and that previously unnoticed cryptic diversity might be present within many lineages, thus urgently requiring a comprehensive taxonomic revision of this primate group. © 2015 The Linnean Society of London PMID:26900177

Locomotion and basicranial anatomy in primates and marsupials.

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Villamil, Catalina I

2017-10-01

There is ongoing debate in paleoanthropology about whether and how the anatomy of the cranium, and especially the cranial base, is evolving in response to locomotor and postural changes. However, the majority of studies focus on two-dimensional data, which fails to capture the complexity of cranial anatomy. This study tests whether three-dimensional cranial base anatomy is linked to locomotion or to other factors in primates (n = 473) and marsupials (n = 231). Results indicate that although there is a small effect of locomotion on cranial base anatomy in primates, this is not the case in marsupials. Instead, facial anatomy likely drives variation in cranial base anatomy in both primates and marsupials, with additional roles for body size and brain size. Although some changes to foramen magnum position and orientation are phylogenetically useful among the hominoids, they do not necessarily reflect locomotion or positional behavior. The interplay between locomotion, posture, and facial anatomy in primates requires further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Nef Proteins Show Distinct Patterns and Mechanisms of Src Kinase Activation

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Greenway, Alison L.; Dutartre, Hélène; Allen, Kelly; McPhee, Dale A.; Olive, Daniel; Collette, Yves

1999-01-01

The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases. PMID:10364375

Primate vocal communication: a useful tool for understanding human speech and language evolution?

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Fedurek, Pawel; Slocombe, Katie E

2011-04-01

Language is a uniquely human trait, and questions of how and why it evolved have been intriguing scientists for years. Nonhuman primates (primates) are our closest living relatives, and their behavior can be used to estimate the capacities of our extinct ancestors. As humans and many primate species rely on vocalizations as their primary mode of communication, the vocal behavior of primates has been an obvious target for studies investigating the evolutionary roots of human speech and language. By studying the similarities and differences between human and primate vocalizations, comparative research has the potential to clarify the evolutionary processes that shaped human speech and language. This review examines some of the seminal and recent studies that contribute to our knowledge regarding the link between primate calls and human language and speech. We focus on three main aspects of primate vocal behavior: functional reference, call combinations, and vocal learning. Studies in these areas indicate that despite important differences, primate vocal communication exhibits some key features characterizing human language. They also indicate, however, that some critical aspects of speech, such as vocal plasticity, are not shared with our primate cousins. We conclude that comparative research on primate vocal behavior is a very promising tool for deepening our understanding of the evolution of human speech and language, but much is still to be done as many aspects of monkey and ape vocalizations remain largely unexplored.

Diagnostic overview of the illegal trade in primates and law enforcement in Peru.

Science.gov (United States)

Shanee, Noga; Mendoza, A Patricia; Shanee, Sam

2017-11-01

Peru has one of the richest primate faunas of any country. The illegal trade in wild primates is one of the largest threats to this fauna in Peru. We characterize the illegal trade in primates through empirical and ethnographic data. We collected data from traffic routes and centers throughout Peru and evaluate current efforts to combat this traffic. Based on our findings from 2,070 instances of wildlife crime involving 6,872 primates, we estimate the domestic trade in primates for pets and bushmeat in Peru in the hundreds of thousands per year, with the larger bodied Atelidae facing the highest direct consequences. We found that government authorities lack sufficient staff, capacity, resources, infrastructure, and protocols to efficiently combat illegal trade in primates. Also, the complicated legal framework and lack of cooperation and antagonism with the public further limit these efforts. Wildlife authorities in Peru are able to confiscate only a fraction of primates traded and mostly intervene in cases of private pet owners rather than traffickers. We estimate that the current rate of illegal trade in primates is comparable to levels of trade prior to the 1973 ban on primates' exportation. The combination of direct observations on primate trade and ethnographic data allows a comprehensive look at primate trade in Peru. We call upon decision makers and international funders to channel their efforts toward "on the ground" actions such as increasing the ability of the authorities to act, giving them "in action" training in law enforcement and establishing strict control measures against corruption. Am. J. Primatol. 79:e22516, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

A Genome-Wide Landscape of Retrocopies in Primate Genomes.

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Navarro, Fábio C P; Galante, Pedro A F

2015-07-29

Gene duplication is a key factor contributing to phenotype diversity across and within species. Although the availability of complete genomes has led to the extensive study of genomic duplications, the dynamics and variability of gene duplications mediated by retrotransposition are not well understood. Here, we predict mRNA retrotransposition and use comparative genomics to investigate their origin and variability across primates. Analyzing seven anthropoid primate genomes, we found a similar number of mRNA retrotranspositions (∼7,500 retrocopies) in Catarrhini (Old Word Monkeys, including humans), but a surprising large number of retrocopies (∼10,000) in Platyrrhini (New World Monkeys), which may be a by-product of higher long interspersed nuclear element 1 activity in these genomes. By inferring retrocopy orthology, we dated most of the primate retrocopy origins, and estimated a decrease in the fixation rate in recent primate history, implying a smaller number of species-specific retrocopies. Moreover, using RNA-Seq data, we identified approximately 3,600 expressed retrocopies. As expected, most of these retrocopies are located near or within known genes, present tissue-specific and even species-specific expression patterns, and no expression correlation to their parental genes. Taken together, our results provide further evidence that mRNA retrotransposition is an active mechanism in primate evolution and suggest that retrocopies may not only introduce great genetic variability between lineages but also create a large reservoir of potentially functional new genomic loci in primate genomes. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Primate dental ecology: How teeth respond to the environment.

Science.gov (United States)

Cuozzo, Frank P; Ungar, Peter S; Sauther, Michelle L

2012-06-01

Teeth are central for the study of ecology, as teeth are at the direct interface between an organism and its environment. Recent years have witnessed a rapid growth in the use of teeth to understand a broad range of topics in living and fossil primate biology. This in part reflects new techniques for assessing ways in which teeth respond to, and interact with, an organism's environment. Long-term studies of wild primate populations that integrate dental analyses have also provided a new context for understanding primate interactions with their environments. These new techniques and long-term field studies have allowed the development of a new perspective-dental ecology. We define dental ecology as the broad study of how teeth respond to, or interact with, the environment. This includes identifying patterns of dental pathology and tooth use-wear, as they reflect feeding ecology, behavior, and habitat variation, including areas impacted by anthropogenic disturbance, and how dental development can reflect environmental change and/or stress. The dental ecology approach, built on collaboration between dental experts and ecologists, holds the potential to provide an important theoretical and practical framework for inferring ecology and behavior of fossil forms, for assessing environmental change in living populations, and for understanding ways in which habitat impacts primate growth and development. This symposium issue brings together experts on dental morphology, growth and development, tooth wear and health, primate ecology, and paleontology, to explore the broad application of dental ecology to questions of how living and fossil primates interact with their environments. Copyright © 2012 Wiley Periodicals, Inc.

Identification of a Conserved Interface of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Vifs with Cullin 5.

Science.gov (United States)

Gu, Qinyong; Zhang, Zeli; Gertzen, Christoph G W; Häussinger, Dieter; Gohlke, Holger; Münk, Carsten

2018-03-15

immunodeficiency virus (FIV), which is similar to human immunodeficiency virus type 1 (HIV-1), replicates in its natural host in T cells and macrophages that express the antiviral restriction factor APOBEC3 (A3). To escape A3s, FIV and HIV induce the degradation of these proteins by building a ubiquitin ligase complex using the viral protein Vif to connect to cellular proteins, including Cullin 5. Here, we identified the protein residues that regulate this interaction in FIV Vif and Cullin 5. While our structural model suggests that the diverse FIV and HIV-1 Vifs use conserved residues for Cullin 5 binding, FIV Vif binds Cullin 5 independently of zinc, in contrast to HIV-1 Vif. Copyright © 2018 American Society for Microbiology.

CCR5 Signal Transduction in Macrophages by Human Immunodeficiency Virus and Simian Immunodeficiency Virus Envelopes

OpenAIRE

Arthos, James; Rubbert, Andrea; Rabin, Ronald L.; Cicala, Claudia; Machado, Elizabeth; Wildt, Kathryne; Hanbach, Meredith; Steenbeke, Tavis D.; Swofford, Ruth; Farber, Joshua M.; Fauci, Anthony S.

2000-01-01

The capacity of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) envelopes to transduce signals through chemokine coreceptors on macrophages was examined by measuring the ability of recombinant envelope proteins to mobilize intracellular calcium stores. Both HIV and SIV envelopes mobilized calcium via interactions with CCR5. The kinetics of these responses were similar to those observed when macrophages were treated with MIP-1β. Distinct differences in the capacity o...

Functional comparison of innate immune signaling pathways in primates.

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Luis B Barreiro

2010-12-01

Full Text Available Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host-virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV-interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases.

Memory B cells and CD8⁺ lymphocytes do not control seasonal influenza A virus replication after homologous re-challenge of rhesus macaques.

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Timothy D Carroll

Full Text Available This study sought to define the role of memory lymphocytes in the protection from homologous influenza A virus re-challenge in rhesus macaques. Depleting monoclonal antibodies (mAb were administered to the animals prior to their second experimental inoculation with a human seasonal influenza A virus strain. Treatment with either anti-CD8α or anti-CD20 mAbs prior to re-challenge had minimal effect on influenza A virus replication. Thus, in non-human primates with pre-existing anti-influenza A antibodies, memory B cells and CD8α⁺ T cells do not contribute to the control of virus replication after re-challenge with a homologous strain of influenza A virus.

Schistosomiasis and infection with human immunodeficiency virus 1 in rural Zimbabwe

DEFF Research Database (Denmark)

Erikstrup, Christian; Kallestrup, Per; Zinyama-Gutsire, Rutendo B L

2008-01-01

We previously reported that treatment for schistosomiasis in persons infected with human immunodeficiency virus 1 (HIV-1) attenuated HIV replication as measured by plasma HIV RNA. We investigated systemic inflammation as measured by plasma levels of soluble tumor necrosis factor-alpha receptor II...... (sTNF-rII), interleukin-8, (IL-8), and IL-10 during schistosomiasis and HIV co-infection and after schistosomiasis treatment. The cohort was composed of 378 persons who were or were not infected with HIV-1, Schistosoma haematobium, or S. mansoni. Schistosomiasis-infected persons were randomized...... to receive praziquantel (40 mg/kg) at baseline or at the three-month follow-up. sTNF-rII and IL-8 were positively associated with schistosomiasis intensity as measured by circulating anodic antigen (CAA), regardless of HIV status. Interleukin-10 was positively associated with CAA in HIV-negative participants...

Tracking Alu evolution in New World primates

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Batzer Mark A

2005-10-01

Full Text Available Abstract Background Alu elements are Short INterspersed Elements (SINEs in primate genomes that have proven useful as markers for studying genome evolution, population biology and phylogenetics. Most of these applications, however, have been limited to humans and their nearest relatives, chimpanzees. In an effort to expand our understanding of Alu sequence evolution and to increase the applicability of these markers to non-human primate biology, we have analyzed available Alu sequences for loci specific to platyrrhine (New World primates. Results Branching patterns along an Alu sequence phylogeny indicate three major classes of platyrrhine-specific Alu sequences. Sequence comparisons further reveal at least three New World monkey-specific subfamilies; AluTa7, AluTa10, and AluTa15. Two of these subfamilies appear to be derived from a gene conversion event that has produced a recently active fusion of AluSc- and AluSp-type elements. This is a novel mode of origin for new Alu subfamilies. Conclusion The use of Alu elements as genetic markers in studies of genome evolution, phylogenetics, and population biology has been very productive when applied to humans. The characterization of these three new Alu subfamilies not only increases our understanding of Alu sequence evolution in primates, but also opens the door to the application of these genetic markers outside the hominid lineage.

A Macaque Model for Rectal Lymphogranuloma Venereum and Non-Lymphogranuloma Venereum Chlamydia trachomatis: Impact on Rectal Simian/Human Immunodeficiency Virus Acquisition.

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Vishwanathan, Sundaram Ajay; Aubert, Rachael D; Morris, Monica R; Zhao, Chunxia; Philips, Christi; Khalil, George M; Deyounks, Frank; Kelley, Kristen; Ritter, Jana M; Chen, C Y; Kersh, Ellen N; McNicholl, Janet M

2017-09-01

Sustained genital tract inflammation caused by sexually transmitted infections (STIs) is known to increase risk of vaginal human immunodeficiency virus (HIV) infections but, to our knowledge, there are no nonhuman primate studies that have evaluated its link to rectal HIV acquisition. Rhesus macaques inoculated with Chlamydia trachomatis (CT) (serovars LGV-L2 and CT-E; n = 7) or saline (n = 7) received up to 20 rectal challenges twice a week of simian/HIV immunodeficiency virus (SHIVSF162p3). SHIV viremia was determined by real-time PCR and Chlamydia infection by APTIMA Combo 2 testing. The rectal cytokine-chemokine levels were evaluated by multiplex bead assays. Rectal Chlamydia infection was maintained throughout the study. We did not observe significant differences (P = 1.0) in frequency of SHIV acquisition between the STI and control arms. It took fewer SHIV challenges to infect the STI animals although the difference was not significant (P = 0.59). There were no significant differences in peak plasma viremia between STI and control arms (P = 0.63). The association of plasma viremia with rectal shedding was significantly different by arm (P = 0.038). In the first such study in a macaque model, we did not observe an increased risk of SHIV acquisition due to rectal Chlamydia coinfection. This macaque model can be further developed and expanded to better investigate the impact of different rectal STIs on HIV acquisition.

Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

Science.gov (United States)

Marzi, Andrea; Yoshida, Reiko; Miyamoto, Hiroko; Ishijima, Mari; Suzuki, Yasuhiko; Higuchi, Megumi; Matsuyama, Yukie; Igarashi, Manabu; Nakayama, Eri; Kuroda, Makoto; Saijo, Masayuki; Feldmann, Friederike; Brining, Douglas; Feldmann, Heinz; Takada, Ayato

2012-01-01

Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.

Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

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Andrea Marzi

Full Text Available Ebola virus (EBOV is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF. Single monoclonal antibodies (MAbs specific for Zaire ebolavirus (ZEBOV have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226 with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.

Euarchontan Opsin Variation Brings New Focus to Primate Origins.

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Melin, Amanda D; Wells, Konstans; Moritz, Gillian L; Kistler, Logan; Orkin, Joseph D; Timm, Robert M; Bernard, Henry; Lakim, Maklarin B; Perry, George H; Kawamura, Shoji; Dominy, Nathaniel J

2016-04-01

Debate on the adaptive origins of primates has long focused on the functional ecology of the primate visual system. For example, it is hypothesized that variable expression of short- (SWS1) and middle-to-long-wavelength sensitive (M/LWS) opsins, which confer color vision, can be used to infer ancestral activity patterns and therefore selective ecological pressures. A problem with this approach is that opsin gene variation is incompletely known in the grandorder Euarchonta, that is, the orders Scandentia (treeshrews), Dermoptera (colugos), and Primates. The ancestral state of primate color vision is therefore uncertain. Here, we report on the genes (OPN1SW and OPN1LW) that encode SWS1 and M/LWS opsins in seven species of treeshrew, including the sole nocturnal scandentian Ptilocercus lowii. In addition, we examined the opsin genes of the Central American woolly opossum (Caluromys derbianus), an enduring ecological analogue in the debate on primate origins. Our results indicate: 1) retention of ultraviolet (UV) visual sensitivity in C. derbianus and a shift from UV to blue spectral sensitivities at the base of Euarchonta; 2) ancient pseudogenization of OPN1SW in the ancestors of P. lowii, but a signature of purifying selection in those of C. derbianus; and, 3) the absence of OPN1LW polymorphism among diurnal treeshrews. These findings suggest functional variation in the color vision of nocturnal mammals and a distinctive visual ecology of early primates, perhaps one that demanded greater spatial resolution under light levels that could support cone-mediated color discrimination. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Scaling of cerebral blood perfusion in primates and marsupials.

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Seymour, Roger S; Angove, Sophie E; Snelling, Edward P; Cassey, Phillip

2015-08-01

The evolution of primates involved increasing body size, brain size and presumably cognitive ability. Cognition is related to neural activity, metabolic rate and rate of blood flow to the cerebral cortex. These parameters are difficult to quantify in living animals. This study shows that it is possible to determine the rate of cortical brain perfusion from the size of the internal carotid artery foramina in skulls of certain mammals, including haplorrhine primates and diprotodont marsupials. We quantify combined blood flow rate in both internal carotid arteries as a proxy of brain metabolism in 34 species of haplorrhine primates (0.116-145 kg body mass) and compare it to the same analysis for 19 species of diprotodont marsupials (0.014-46 kg). Brain volume is related to body mass by essentially the same exponent of 0.70 in both groups. Flow rate increases with haplorrhine brain volume to the 0.95 power, which is significantly higher than the exponent (0.75) expected for most organs according to 'Kleiber's Law'. By comparison, the exponent is 0.73 in marsupials. Thus, the brain perfusion rate increases with body size and brain size much faster in primates than in marsupials. The trajectory of cerebral perfusion in primates is set by the phylogenetically older groups (New and Old World monkeys, lesser apes) and the phylogenetically younger groups (great apes, including humans) fall near the line, with the highest perfusion. This may be associated with disproportionate increases in cortical surface area and mental capacity in the highly social, larger primates. © 2015. Published by The Company of Biologists Ltd.

Primary immunodeficiencies and B-cell lymphomas.

Science.gov (United States)

Martín-Mateos, María Anunciación; Piquer Gibert, Mónica

In primary immunodeficiencies there is a failure in the anti-tumor defense. Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies characterized by an alteration in the differentiation of B lymphocytes (BL). Epstein-Barr virus (EBV) is an ubiquitous virus that selectively infects the BL. In patients with immunodeficiency, uncontrolled proliferation of infected BL and the action of viral proteins promote the development of lymphomas. At the University Hospital Sant Joan de Deu, Barcelona, 28 patients were diagnosed with CVID from 2000 to 2013. This paper describes four patients who developed non-Hodgkin's lymphoma (NHL). The lymphoma was associated with EBV in two of the cases. Patients were<18 years old, diagnosed with lymphoma between 4 and 13 years old. Two patients were treated with rituximab as monotherapy and achieved complete remission. Two patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and radiotherapy or rituximab and achieved complete remission. Early detection of EBV infections and NHL in all patients diagnosed with CVID is recommended, regardless of age at diagnosis. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

A constitutive damage specific DNA-binding protein is synthesized at higher levels in UV-irradiated primate cells

International Nuclear Information System (INIS)

Hirschfeld, S.; Levine, A.S.; Ozato, K.; Protic, M.

1990-01-01

Using a DNA band shift assay, we have identified a DNA-binding protein complex in primate cells which is present constitutively and has a high affinity for UV-irradiated, double-stranded DNA. Cells pretreated with UV light, mitomycin C, or aphidicolin have higher levels of this damage-specific DNA-binding protein complex, suggesting that the signal for induction can either be damage to the DNA or interference with cellular DNA replication. Physiochemical modifications of the DNA and competition analysis with defined substrates suggest that the most probable target site for the damage-specific DNA-binding protein complex is a 6-4'-(pyrimidine-2'-one)-pyrimidine dimer: specific binding could not be detected with probes which contain -TT- cyclobutane dimers, and damage-specific DNA binding did not decrease after photoreactivation of UV-irradiated DNA. This damage-specific DNA-binding protein complex is the first such inducible protein complex identified in primate cells. Cells from patients with the sun-sensitive cancer-prone disease, xeroderma pigmentosum (group E), are lacking both the constitutive and the induced damage-specific DNA-binding activities. These findings suggest a possible role for this DNA-binding protein complex in lesion recognition and DNA repair of UV-light-induced photoproducts

Eocene primates of South America and the African origins of New World monkeys

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Bond, Mariano; Tejedor, Marcelo F.; Campbell, Kenneth E.; Chornogubsky, Laura; Novo, Nelson; Goin, Francisco

2015-04-01

The platyrrhine primates, or New World monkeys, are immigrant mammals whose fossil record comes from Tertiary and Quaternary sediments of South America and the Caribbean Greater Antilles. The time and place of platyrrhine origins are some of the most controversial issues in primate palaeontology, although an African Palaeogene ancestry has been presumed by most primatologists. Until now, the oldest fossil records of New World monkeys have come from Salla, Bolivia, and date to approximately 26 million years ago, or the Late Oligocene epoch. Here we report the discovery of new primates from the ?Late Eocene epoch of Amazonian Peru, which extends the fossil record of primates in South America back approximately 10 million years. The new specimens are important for understanding the origin and early evolution of modern platyrrhine primates because they bear little resemblance to any extinct or living South American primate, but they do bear striking resemblances to Eocene African anthropoids, and our phylogenetic analysis suggests a relationship with African taxa. The discovery of these new primates brings the first appearance datum of caviomorph rodents and primates in South America back into close correspondence, but raises new questions about the timing and means of arrival of these two mammalian groups.

Increased neutralization sensitivity and reduced replicative capacity of human immunodeficiency virus type 1 after short-term in vivo or in vitro passage through chimpanzees

NARCIS (Netherlands)

Beaumont, T.; Broersen, S.; van Nuenen, A.; Huisman, H. G.; de Roda Husman, A. M.; Heeney, J. L.; Schuitemaker, H.

2000-01-01

Development of disease is extremely rare in chimpanzees when inoculated with either T-cell-line-adapted neutralization-sensitive or primary human immunodeficiency virus type 1 (HIV-1), at first excluding a role for HIV-1 neutralization sensitivity in the clinical course of infection. Interestingly,

Seroprevalence of Hepatitis A virus infection in non-human primates in Assam, India

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B.G. Nath

2013-08-01

Full Text Available The present study investigated 37 serum samples of non-human primates in Assam State Zoo and the Department of Forest and Environment, Govt. of Assam for seroprevalence of hepatitis A virus infection during the period from December, 2007 to November, 2009. Four serum samples were also collected from animal keepers of the zoo to investigate transmission of the disease to the attendants working with these primates. Competitive ELISA was performed using hepatitis A virus ELISA kit (Wanti Hep. AV to detect hepatitis A virus antibody in serum samples. Ten (27.21% of the non-human primate samples and three (75% human samples had detectable anti-hepatitis A virus antibodies. Living status of the non-human primates (Free living was a high potential risk for hepatitis A virus infection. Seroprevalence of hepatitis A virus infection had significant difference between free living non-human primates and captive non-human primates (P less than 0.05. No significant difference (p=0.86 was seen between male and female non-human primates

Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication

DEFF Research Database (Denmark)

Meschi, Joseph; Crouch, Erika C; Skolnik, Paul

2005-01-01

The envelope protein (gp120) of human immunodeficiency virus (HIV) contains highly conserved mannosylated oligosaccharides. These glycoconjugates contribute to resistance to antibody neutralization, and binding to cell surface lectins on macrophages and dendritic cells. Mannose-binding lectin (MBL......) binds to gp120 and plays a role in defence against the virus. In this study it is demonstrated that surfactant protein D (SP-D) binds to gp120 and inhibits HIV infectivity at significantly lower concentrations than MBL. The binding of SP-D was mediated by its calcium-dependent carbohydrate......-binding activity and was dependent on glycosylation of gp120. Native dodecameric SP-D bound to HIV gp120 more strongly than native trimeric SP-D. Since one common polymorphic form of SP-D is predominantly expressed as trimers and associated with lower blood levels, these individuals may have less effective innate...

The coevolution of play and the cortico-cerebellar system in primates.

Science.gov (United States)

Kerney, Max; Smaers, Jeroen B; Schoenemann, P Thomas; Dunn, Jacob C

2017-10-01

Primates are some of the most playful animals in the natural world, yet the reason for this remains unclear. One hypothesis posits that primates are so playful because playful activity functions to help develop the sophisticated cognitive and behavioural abilities that they are also renowned for. If this hypothesis were true, then play might be expected to have coevolved with the neural substrates underlying these abilities in primates. Here, we tested this prediction by conducting phylogenetic comparative analyses to determine whether play has coevolved with the cortico-cerebellar system, a neural system known to be involved in complex cognition and the production of complex behaviour. We used phylogenetic generalised least squares analyses to compare the relative volume of the largest constituent parts of the primate cortico-cerebellar system (prefrontal cortex, non-prefrontal heteromodal cortical association areas, and posterior cerebellar hemispheres) to the mean percentage of time budget spent in play by a sample of primate species. Using a second categorical data set on play, we also used phylogenetic analysis of covariance to test for significant differences in the volume of the components of the cortico-cerebellar system among primate species exhibiting one of three different levels of adult-adult social play. Our results suggest that, in general, a positive association exists between the amount of play exhibited and the relative size of the main components of the cortico-cerebellar system in our sample of primate species. Although the explanatory power of this study is limited by the correlational nature of its analyses and by the quantity and quality of the data currently available, this finding nevertheless lends support to the hypothesis that play functions to aid the development of cognitive and behavioural abilities in primates.

Optical tweezers reveal how proteins alter replication

Science.gov (United States)

Chaurasiya, Kathy

Single molecule force spectroscopy is a powerful method that explores the DNA interaction properties of proteins involved in a wide range of fundamental biological processes such as DNA replication, transcription, and repair. We use optical tweezers to capture and stretch a single DNA molecule in the presence of proteins that bind DNA and alter its mechanical properties. We quantitatively characterize the DNA binding mechanisms of proteins in order to provide a detailed understanding of their function. In this work, we focus on proteins involved in replication of Escherichia coli (E. coli ), endogenous eukaryotic retrotransposons Ty3 and LINE-1, and human immunodeficiency virus (HIV). DNA polymerases replicate the entire genome of the cell, and bind both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) during DNA replication. The replicative DNA polymerase in the widely-studied model system E. coli is the DNA polymerase III subunit alpha (DNA pol III alpha). We use optical tweezers to determine that UmuD, a protein that regulates bacterial mutagenesis through its interactions with DNA polymerases, specifically disrupts alpha binding to ssDNA. This suggests that UmuD removes alpha from its ssDNA template to allow DNA repair proteins access to the damaged DNA, and to facilitate exchange of the replicative polymerase for an error-prone translesion synthesis (TLS) polymerase that inserts nucleotides opposite the lesions, so that bacterial DNA replication may proceed. This work demonstrates a biophysical mechanism by which E. coli cells tolerate DNA damage. Retroviruses and retrotransposons reproduce by copying their RNA genome into the nuclear DNA of their eukaryotic hosts. Retroelements encode proteins called nucleic acid chaperones, which rearrange nucleic acid secondary structure and are therefore required for successful replication. The chaperone activity of these proteins requires strong binding affinity for both single- and double-stranded nucleic

Trabecular architecture of the manual elements reflects locomotor patterns in primates.

Science.gov (United States)

Matarazzo, Stacey A

2015-01-01

The morphology of trabecular bone has proven sensitive to loading patterns in the long bones and metacarpal heads of primates. It is expected that we should also see differences in the manual digits of primates that practice different methods of locomotion. Primate proximal and middle phalanges are load-bearing elements that are held in different postures and experience different mechanical strains during suspension, quadrupedalism, and knuckle walking. Micro CT scans of the middle phalanx, proximal phalanx and the metacarpal head of the third ray were used to examine the pattern of trabecular orientation in Pan, Gorilla, Pongo, Hylobates and Macaca. Several zones, i.e., the proximal ends of both phalanges and the metacarpal heads, were capable of distinguishing between knuckle-walking, quadrupedal, and suspensory primates. Orientation and shape seem to be the primary distinguishing factors but differences in bone volume, isotropy index, and degree of anisotropy were seen across included taxa. Suspensory primates show primarily proximodistal alignment in all zones, and quadrupeds more palmar-dorsal orientation in several zones. Knuckle walkers are characterized by having proximodistal alignment in the proximal ends of the phalanges and a palmar-dorsal alignment in the distal ends and metacarpal heads. These structural differences may be used to infer locmotor propensities of extinct primate taxa.

Ocular toxoplasmosis in immunosuppressed nonhuman primates

International Nuclear Information System (INIS)

Holland, G.N.; O'Connor, G.R.; Diaz, R.F.; Minasi, P.; Wara, W.M.

1988-01-01

To investigate the role of cellular immunodeficiency in recurrent toxoplasmic retinochoroiditis, six Cynomolgus monkeys (Macaca fascicularis) with healed toxoplasmic lesions of the retina were immunosuppressed by total lymphoid irradiation. Three months prior to irradiation 30,000 Toxoplasma gondii organisms of the Beverley strain had been inoculated onto the macula of eye in each monkey via a pars plana approach. Toxoplasmic retinochoroiditis developed in each animal, and lesions were allowed to heal without treatment. During total lymphoid irradiation animals received 2000 centigrays (cGy) over a 7-week period. Irradiation resulted in an immediate drop in total lymphocyte counts and decreased ability to stimulate lymphocytes by phytohemagglutinin. Weekly ophthalmoscopic examinations following irradiation failed to show evidence of recurrent ocular disease despite persistent immunodeficiency. Four months after irradiation live organisms were reinoculated onto the nasal retina of the same eye in each animal. Retinochoroidal lesions identical to those seen in primary disease developed in five of six animals. Toxoplasma organisms therefore were able to proliferate in ocular tissue following the administration of immunosuppressive therapy. This study fails to support the hypothesis that cellular immunodeficiency alone will initiate recurrent toxoplasmic retinochoroiditis. Results suggest that reactivation of disease from encysted organisms involves factors other than suppression of Toxoplasma proliferation. If reactivation occurs by other mechanisms, however, cellular immunodeficiency then may allow development of extensive disease

Ocular toxoplasmosis in immunosuppressed nonhuman primates

Energy Technology Data Exchange (ETDEWEB)

Holland, G.N.; O' Connor, G.R.; Diaz, R.F.; Minasi, P.; Wara, W.M.

1988-06-01

To investigate the role of cellular immunodeficiency in recurrent toxoplasmic retinochoroiditis, six Cynomolgus monkeys (Macaca fascicularis) with healed toxoplasmic lesions of the retina were immunosuppressed by total lymphoid irradiation. Three months prior to irradiation 30,000 Toxoplasma gondii organisms of the Beverley strain had been inoculated onto the macula of eye in each monkey via a pars plana approach. Toxoplasmic retinochoroiditis developed in each animal, and lesions were allowed to heal without treatment. During total lymphoid irradiation animals received 2000 centigrays (cGy) over a 7-week period. Irradiation resulted in an immediate drop in total lymphocyte counts and decreased ability to stimulate lymphocytes by phytohemagglutinin. Weekly ophthalmoscopic examinations following irradiation failed to show evidence of recurrent ocular disease despite persistent immunodeficiency. Four months after irradiation live organisms were reinoculated onto the nasal retina of the same eye in each animal. Retinochoroidal lesions identical to those seen in primary disease developed in five of six animals. Toxoplasma organisms therefore were able to proliferate in ocular tissue following the administration of immunosuppressive therapy. This study fails to support the hypothesis that cellular immunodeficiency alone will initiate recurrent toxoplasmic retinochoroiditis. Results suggest that reactivation of disease from encysted organisms involves factors other than suppression of Toxoplasma proliferation. If reactivation occurs by other mechanisms, however, cellular immunodeficiency then may allow development of extensive disease.

Multimedia in Anthropology: A Guide to the Nonhuman Primates.

Science.gov (United States)

Burton, Frances D.

This paper describes a primatology project using computer assisted learning and interactive multimedia to help students at the University of Toronto (Canada) learn about non-human primates. The purpose of the interactive program is to present the "natural history" of the majority of the 200-plus species of non-human primates in constant…

Antigenic relatedness of primate procollagens as determined by a competitive radioimmunoassay

International Nuclear Information System (INIS)

Taubman, M.B.; Goldberg, B.

1978-01-01

A radioimmunoassay specific for the nonhelical carboxy terminal portion of human type I procollagen was used to study the antigenic relatedness of primate procollagens. The assay identified reactive antigen in primate sera and in the media of primate fibroblast cultures. The displacement curves generated in the assay indicated that human and ape type I procollagens have antigenically identical carboxy terminal determinants which are partially cross-reactive with those from Old and New World monkeys. (author)

A simple fluorescence based assay for quantification of human immunodeficiency virus particle release

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Heuser Anke-Mareil

2010-04-01

Full Text Available Abstract Background The assembly and release of human immunodeficiency virus (HIV particles from infected cells represent attractive, but not yet exploited targets for antiretroviral therapy. The availability of simple methods to measure the efficiency of these replication steps in tissue culture would facilitate the identification of host factors essential for these processes as well as the screening for lead compounds acting as specific inhibitors of particle formation. We describe here the development of a rapid cell based assay for quantification of human immunodeficiency virus type 1 (HIV-1 particle assembly and/or release. Results Using a fluorescently labelled HIV-derivative, which carries an eYFP domain within the main viral structural protein Gag in the complete viral protein context, the release of virus like particles could be monitored by directly measuring the fluorescence intensity of the tissue culture supernatant. Intracellular Gag was quantitated in parallel by direct fluorescence analysis of cell lysates, allowing us to normalize for Gag expression efficiency. The assay was validated by comparison with p24 capsid ELISA measurements, a standard method for quantifying HIV-1 particles. Optimization of conditions allowed the robust detection of particle amounts corresponding to 50 ng p24/ml in medium by fluorescence spectroscopy. Further adaptation to a multi-well format rendered the assay suitable for medium or high throughput screening of siRNA libraries to identify host cell factors involved in late stages of HIV replication, as well as for random screening approaches to search for potential inhibitors of HIV-1 assembly or release. Conclusions The fast and simple fluorescence based quantification of HIV particle release yielded reproducible results which were comparable to the well established ELISA measurements, while in addition allowing the parallel determination of intracellular Gag expression. The protocols described here

Social learning of vocal structure in a nonhuman primate?

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Lemasson Alban

2011-12-01

Full Text Available Abstract Background Non-human primate communication is thought to be fundamentally different from human speech, mainly due to vast differences in vocal control. The lack of these abilities in non-human primates is especially striking if compared to some marine mammals and bird species, which has generated somewhat of an evolutionary conundrum. What are the biological roots and underlying evolutionary pressures of the human ability to voluntarily control sound production and learn the vocal utterances of others? One hypothesis is that this capacity has evolved gradually in humans from an ancestral stage that resembled the vocal behavior of modern primates. Support for this has come from studies that have documented limited vocal flexibility and convergence in different primate species, typically in calls used during social interactions. The mechanisms underlying these patterns, however, are currently unknown. Specifically, it has been difficult to rule out explanations based on genetic relatedness, suggesting that such vocal flexibility may not be the result of social learning. Results To address this point, we compared the degree of acoustic similarity of contact calls in free-ranging Campbell's monkeys as a function of their social bonds and genetic relatedness. We calculated three different indices to compare the similarities between the calls' frequency contours, the duration of grooming interactions and the microsatellite-based genetic relatedness between partners. We found a significantly positive relation between bond strength and acoustic similarity that was independent of genetic relatedness. Conclusion Genetic factors determine the general species-specific call repertoire of a primate species, while social factors can influence the fine structure of some the call types. The finding is in line with the more general hypothesis that human speech has evolved gradually from earlier primate-like vocal communication.

Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress.

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Zhang, Xiao-Liang; Pang, Wei; Hu, Xin-Tian; Li, Jia-Li; Yao, Yong-Gang; Zheng, Yong-Tang

2014-11-18

Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China.

Adaptive evolution of facial colour patterns in Neotropical primates.

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Santana, Sharlene E; Lynch Alfaro, Jessica; Alfaro, Michael E

2012-06-07

The rich diversity of primate faces has interested naturalists for over a century. Researchers have long proposed that social behaviours have shaped the evolution of primate facial diversity. However, the primate face constitutes a unique structure where the diverse and potentially competing functions of communication, ecology and physiology intersect, and the major determinants of facial diversity remain poorly understood. Here, we provide the first evidence for an adaptive role of facial colour patterns and pigmentation within Neotropical primates. Consistent with the hypothesis that facial patterns function in communication and species recognition, we find that species living in smaller groups and in sympatry with a higher number of congener species have evolved more complex patterns of facial colour. The evolution of facial pigmentation and hair length is linked to ecological factors, and ecogeographical rules related to UV radiation and thermoregulation are met by some facial regions. Our results demonstrate the interaction of behavioural and ecological factors in shaping one of the most outstanding facial diversities of any mammalian lineage.

Multiple groups of endogenous epsilon-like retroviruses conserved across primates.

Science.gov (United States)

Brown, Katherine; Emes, Richard D; Tarlinton, Rachael E

2014-11-01

Several types of cancer in fish are caused by retroviruses, including those responsible for major outbreaks of disease, such as walleye dermal sarcoma virus and salmon swim bladder sarcoma virus. These viruses form a phylogenetic group often described as the epsilonretrovirus genus. Epsilon-like retroviruses have become endogenous retroviruses (ERVs) on several occasions, integrating into germ line cells to become part of the host genome, and sections of fish and amphibian genomes are derived from epsilon-like retroviruses. However, epsilon-like ERVs have been identified in very few mammals. We have developed a pipeline to screen full genomes for ERVs, and using this pipeline, we have located over 800 endogenous epsilon-like ERV fragments in primate genomes. Genomes from 32 species of mammals and birds were screened, and epsilon-like ERV fragments were found in all primate and tree shrew genomes but no others. These viruses appear to have entered the genome of a common ancestor of Old and New World monkeys between 42 million and 65 million years ago. Based on these results, there is an ancient evolutionary relationship between epsilon-like retroviruses and primates. Clearly, these viruses had the potential to infect the ancestors of primates and were at some point a common pathogen in these hosts. Therefore, this result raises questions about the potential of epsilonretroviruses to infect humans and other primates and about the evolutionary history of these retroviruses. Epsilonretroviruses are a group of retroviruses that cause several important diseases in fish. Retroviruses have the ability to become a permanent part of the DNA of their host by entering the germ line as endogenous retroviruses (ERVs), where they lose their infectivity over time but can be recognized as retroviruses for millions of years. Very few mammals are known to have epsilon-like ERVs; however, we have identified over 800 fragments of endogenous epsilon-like ERVs in the genomes of all major

Spinal cord toxoplasmosis in human immunodeficiency virus infection/acquired immunodeficiency syndrome.

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García-García, Concepción; Castillo-Álvarez, Federico; Azcona-Gutiérrez, José M; Herraiz, María J; Ibarra, Valvanera; Oteo, José A

2015-05-01

Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.

Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy

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Salgado Maria

2011-12-01

Full Text Available Abstract Background While initiation of highly active antiretroviral therapy (HAART during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in plasma viremia. Results Here we report a case of a patient who was started on HAART during symptomatic primary infection and who has subsequently maintained viral loads of + T cells. In addition, he does not have any known protective HLA alleles. Thus it is unlikely that he was destined to become a natural elite controller or suppressor. The mechanism of control of viral replication is unclear; he is infected with a CCR5/CXCR4 dual-tropic virus that is fully replication-competent in vitro. In addition, his spouse, who transmitted the virus to him, developed AIDS. The patient's CD4+ T cells are fully susceptible to HIV-1 infection, and he has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates. Furthermore, his CD8+ T cells do not have potent HIV suppressive activity. Conclusion This report suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte (CTL mediated suppression that has been reported in many elite suppressors.

Immunodeficiencies and autoimmune diseases: common variable immunodeficiency and Crohn-like

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Cristina Saldaña-Dueñas

Full Text Available Background: Common variable immunodeficiency (CVI gives a major risk of principally respiratory and digestive infections. It is associated with autoimmune diseases, granulomatous process and neoplasias. The digestive clinic is common, in 10% of patients it is the only symptom, and 60% present chronic diarrhea. Clinically it can be confused and related with other pathologies such as inflammatory bowel disease which is infrequent (2-13%. Case report: We present the case of a patient with CVI with digestive symptoms being diagnosed of Crohn-like disease with extent ileal affectation. The main treatment of these patients is the same as classical Crohn disease although in the most severe cases, as this one, the use of immunosupresors is necessary. At this time the patient remains on clinical remmision with infliximab. She presented a previous adverse reaction with adalimumab. Discussion: The few case series in this pathology makes the treatment with immunomodulators in this immunodeficiency a real diagnostic and therapeutic challenge.

How effective are the 6 European Society of Immunodeficiency warning signs for primary immunodeficiency disease?

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Arslan, Sevket; Ucar, Ramazan; Caliskaner, Ahmet Zafer; Reisli, Ismail; Guner, Sukru Nail; Sayar, Esra Hazar; Baloglu, Ismail

2016-02-01

The European Society of Immunodeficiency (ESID) developed 6 warning signs to promote the awareness of adult primary immunodeficiency disease (PID). To screen adult patients for the presence of PID using these 6 warning signs to determine the effectiveness of this protocol. Questions related to the ESID warning signs for adult PID were added to the standard outpatient clinic file system and asked of 3,510 patients who were admitted to our clinic for any reason. Patients with signs and/or suspicion of PID based on their medical history underwent immunologic investigation. In total, 24 patients were diagnosed as having a PID. The most common reason that patients with PID were admitted was frequent infection (n=18 [75%]), and the most common PID subgroup was common variable immunodeficiency (n=12 [50%]). Twenty patients with PID had at least one positive finding according to the ESID warning signs. Two patients with gastrointestinal concerns and 2 with dermatologic symptoms were also diagnosed as having a PID, although they did not have any of the ESID warning signs. The ESID warning signs do not specify the need for symptoms to diagnose a PIDs and do not include a comprehensive list of all signs and symptoms of PIDs. As a result, more than infection-centric questions are needed to identify adult patients with immunodeficiencies. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Introduction to the Handbook of Primate Behavioral Management

DEFF Research Database (Denmark)

Schapiro, Steve

2017-01-01

of behavioral management programs for nonhuman primates (NHPs) with a plethora of information, guidance, and data that will allow them to do everything within their power to guarantee that their animals are living in the best conditions possible. A more specific goal involves the presentation of the science......Welcome to the Handbook of Primate Behavioral Management (HPBM). This handbook contains 29 chapters divided into six parts, all of which focus on aspects of primate behavioral management. The overall goal of the HPBM is to provide those responsible for the development and/or implementation...... of behavioral management, so that behavioral managers can base their decisions on relevant empirical evidence. If the data show that the subadult male offspring of high-ranking females cause social instability in large groups of rhesus macaques living in field cages (McCowan and Beisner 2017...

Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies.

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Brian J Willett

Full Text Available Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV, a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1 or diverse (Group 2 challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development.

Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen presenting cells and induces efficient CD4+ T helper responses.

OpenAIRE

Fiorentini, Simona; Marconi, Peggy; Avolio, Manuela; Marini, Elena; Garrafa, Emirena; Caracciolo, Sonia; Rossi, Daniele; Bozac, Alexandra; Becker, Pablo D; Gentili, Francesca; Facchetti, Fabio; Guzman, Carlos A; Manservigi, Roberto; Caruso, Arnaldo

2007-01-01

Both neutralizing antibodies and cytotoxic T-cells are necessary to control a viral infection. However, vigorous T helper responses are essential for their elicitation and maintenance. Here we show that a recombinant replication-deficient Herpes Simplex Virus (HSV)-1 vector encoding the Human Immunodeficiency Virus (HIV)-1 matrix protein p17 (T0-p17) was capable of infecting professional antigen presenting cells (APCs) in vitro and in vivo. The injection of T0-p17 in the mouse dermis generate...

Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome.

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Huang, Yan-Mei; Hong, Xue-Zhi; Xu, Jia-Hua; Luo, Jiang-Xi; Mo, Han-You; Zhao, Hai-Lu

2016-06-01

Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis.

Utilizing a TLR5-Adjuvanted Cytomegalovirus as a Lentiviral Vaccine in the Nonhuman Primate Model for AIDS.

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Jesse D Deere

Full Text Available Despite tremendous progress in our understanding of human immunodeficiency virus (HIV natural history and advances in HIV treatment, there is neither an approved vaccine nor a cure for infection. Here, we describe the development and characterization of a novel replicating vaccine vector utilizing Cytomegalovirus (CMV and a TLR5 adjuvant. After partial truncation of the central, immunodominant hypervariable domain, flagellin (fliC from Salmonella was cloned downstream of a codon optimized gag gene from simian immunodeficiency virus (SIV and transiently expressed in telomerized rhesus fibroblast (TeloRF cells in culture. Lysates generated from these transfected cells induced the tumor necrosis factor alpha (TNF-α, in a mouse macrophage cell line, in a TLR5-dependent manner. The Gag/FliC expression construct was cloned into a bacterial artificial chromosome encoding the rhesus CMV (RhCMV genome, and infectious RhCMV was generated following transfection of TeloRF cells. This virus stably expressed an SIV Gag/FliC fusion protein through four serial passages. Lysates generated from infected cells induced TNF-α in a TLR5-dependent manner. Western blot analysis of infected cell lysates verified expression of a Gag/FliC fusion protein using a SIV p27 capsid monoclonal antibody. Lastly, rhesus macaques inoculated with this novel RhCMV virus demonstrated increased inflammatory responses at the site of inoculation seven days post-infection when compared to the parental RhCMV. These results demonstrate that an artificially constructed replicating RhCMV expressing an SIV Gag/FliC fusion protein is capable of activating TLR5 in a macrophage cell line in vitro and induction of an altered inflammatory response in vivo. Ongoing animals studies are aimed at determining vaccine efficacy, including subsequent challenge with pathogenic SIV.

The role of invasive trophoblast in implantation and placentation of primates

DEFF Research Database (Denmark)

Carter, Anthony Michael; Enders, Allen C; Pijnenborg, Robert

2015-01-01

We here review the evolution of invasive placentation in primates towards the deep penetration of the endometrium and its arteries in hominoids. The strepsirrhine primates (lemurs and lorises) have non-invasive, epitheliochorial placentation, although this is thought to be derived from a more...... invasive type. In haplorhine primates, there is differentiation of trophoblast at the blastocyst stage into syncytial and cellular trophoblast. Implantation involves syncytiotrophoblast that first removes the uterine epithelium then consolidates at the basal lamina before continuing into the stroma...

Looking forward to a PET scanner designed for non-human primates

International Nuclear Information System (INIS)

Tanaka, Keiji

1992-01-01

The cerebral cortex of non-human primates has been divided, mainly by anatomical techniques, into an enormous number of areas. We are looking forward to a PET scanner designed for non-human primates, with a hope to determine active brain regions when the animal does various cognitive tasks. This measurement with PET can be combined with single cell recordings and anatomical tracer studies in non-human primates. Another big hope is to detect a change of active regions as the learning advances. (author)

Pervasive Adaptive Evolution in Primate Seminal Proteins.

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2005-09-01

Full Text Available Seminal fluid proteins show striking effects on reproduction, involving manipulation of female behavior and physiology, mechanisms of sperm competition, and pathogen defense. Strong adaptive pressures are expected for such manifestations of sexual selection and host defense, but the extent of positive selection in seminal fluid proteins from divergent taxa is unknown. We identified adaptive evolution in primate seminal proteins using genomic resources in a tissue-specific study. We found extensive signatures of positive selection when comparing 161 human seminal fluid proteins and 2,858 prostate-expressed genes to those in chimpanzee. Seven of eight outstanding genes yielded statistically significant evidence of positive selection when analyzed in divergent primates. Functional clues were gained through divergent analysis, including several cases of species-specific loss of function in copulatory plug genes, and statistically significant spatial clustering of positively selected sites near the active site of kallikrein 2. This study reveals previously unidentified positive selection in seven primate seminal proteins, and when considered with findings in Drosophila, indicates that extensive positive selection is found in seminal fluid across divergent taxonomic groups.

A chimeric measles virus with a lentiviral envelope replicates exclusively in CD4+/CCR5+ cells

International Nuclear Information System (INIS)

Mourez, Thomas; Mesel-Lemoine, Mariana; Combredet, Chantal; Najburg, Valerie; Cayet, Nadege; Tangy, Frederic

2011-01-01

We generated a replicating chimeric measles virus in which the hemagglutinin and fusion surface glycoproteins were replaced with the gp160 envelope glycoprotein of simian immunodeficiency virus (SIVmac239). Based on a previously cloned live-attenuated Schwarz vaccine strain of measles virus (MV), this chimera was rescued at high titers using reverse genetics in CD4+ target cells. Cytopathic effect consisted in the presence of large cell aggregates evolving to form syncytia, as observed during SIV infection. The morphology of the chimeric virus was identical to that of the parent MV particles. The presence of SIV gp160 as the only envelope protein on chimeric particles surface altered the cell tropism of the new virus from CD46+ to CD4+ cells. Used as an HIV candidate vaccine, this MV/SIVenv chimeric virus would mimic transient HIV-like infection, benefiting both from HIV-like tropism and the capacity of MV to replicate in dendritic cells, macrophages and lymphocytes.

Replicating Rather than Nonreplicating Adenovirus-Human Immunodeficiency Virus Recombinant Vaccines Are Better at Eliciting Potent Cellular Immunity and Priming High-Titer Antibodies

OpenAIRE

Peng, Bo; Wang, Liqun Rejean; Gómez-Román, Victor Raúl; Davis-Warren, Alberta; Montefiori, David C.; Kalyanaraman, V. S.; Venzon, David; Zhao, Jun; Kan, Elaine; Rowell, Thomas J.; Murthy, Krishna K.; Srivastava, Indresh; Barnett, Susan W.; Robert-Guroff, Marjorie

2005-01-01

A major challenge in combating the human immunodeficiency virus (HIV) epidemic is the development of vaccines capable of inducing potent, persistent cellular immunity and broadly reactive neutralizing antibody responses to HIV type 1 (HIV-1). We report here the results of a preclinical trial using the chimpanzee model to investigate a combination vaccine strategy involving sequential priming immunizations with different serotypes of adenovirus (Ad)/HIV-1MNenv/rev recombinants and boosting wit...

Sequential priming with simian immunodeficiency virus (SIV) DNA vaccines, with or without encoded cytokines, and a replicating adenovirus-SIV recombinant followed by protein boosting does not control a pathogenic SIVmac251 mucosal challenge.

Science.gov (United States)

Demberg, Thorsten; Boyer, Jean D; Malkevich, Nina; Patterson, L Jean; Venzon, David; Summers, Ebonita L; Kalisz, Irene; Kalyanaraman, V S; Lee, Eun Mi; Weiner, David B; Robert-Guroff, Marjorie

2008-11-01

Previously, combination DNA/nonreplicating adenovirus (Ad)- or poxvirus-vectored vaccines have strongly protected against SHIV(89.6P), DNAs expressing cytokines have modulated immunity elicited by DNA vaccines, and replication-competent Ad-recombinant priming and protein boosting has strongly protected against simian immunodeficiency virus (SIV) challenge. Here we evaluated a vaccine strategy composed of these promising components. Seven rhesus macaques per group were primed twice with multigenic SIV plasmid DNA with or without interleukin-12 (IL-12) DNA or IL-15 DNA. After a multigenic replicating Ad-SIV immunization, all groups received two booster immunizations with SIV gp140 and SIV Nef protein. Four control macaques received control DNA plasmids, empty Ad vector, and adjuvant. All vaccine components were immunogenic, but the cytokine DNAs had little effect. Macaques that received IL-15-DNA exhibited higher peak anti-Nef titers, a more rapid anti-Nef anamnestic response postchallenge, and expanded CD8(CM) T cells 2 weeks postchallenge compared to the DNA-only group. Other immune responses were indistinguishable between groups. Overall, no protection against intrarectal challenge with SIV(mac251) was observed, although immunized non-Mamu-A*01 macaques as a group exhibited a statistically significant 1-log decline in acute viremia compared to non-Mamu-A*01 controls. Possible factors contributing to the poor outcome include administration of cytokine DNAs to sites different from the Ad recombinants (intramuscular and intratracheal, respectively), too few DNA priming immunizations, a suboptimal DNA delivery method, failure to ensure delivery of SIV and cytokine plasmids to the same cell, and instability and short half-life of the IL-15 component. Future experiments should address these issues to determine if this combination approach is able to control a virulent SIV challenge.

Inversion variants in human and primate genomes.

Science.gov (United States)

Catacchio, Claudia Rita; Maggiolini, Flavia Angela Maria; D'Addabbo, Pietro; Bitonto, Miriana; Capozzi, Oronzo; Signorile, Martina Lepore; Miroballo, Mattia; Archidiacono, Nicoletta; Eichler, Evan E; Ventura, Mario; Antonacci, Francesca

2018-05-18

For many years, inversions have been proposed to be a direct driving force in speciation since they suppress recombination when heterozygous. Inversions are the most common large-scale differences among humans and great apes. Nevertheless, they represent large events easily distinguishable by classical cytogenetics, whose resolution, however, is limited. Here, we performed a genome-wide comparison between human, great ape, and macaque genomes using the net alignments for the most recent releases of genome assemblies. We identified a total of 156 putative inversions, between 103 kb and 91 Mb, corresponding to 136 human loci. Combining literature, sequence, and experimental analyses, we analyzed 109 of these loci and found 67 regions inverted in one or multiple primates, including 28 newly identified inversions. These events overlap with 81 human genes at their breakpoints, and seven correspond to sites of recurrent rearrangements associated with human disease. This work doubles the number of validated primate inversions larger than 100 kb, beyond what was previously documented. We identified 74 sites of errors, where the sequence has been assembled in the wrong orientation, in the reference genomes analyzed. Our data serve two purposes: First, we generated a map of evolutionary inversions in these genomes representing a resource for interrogating differences among these species at a functional level; second, we provide a list of misassembled regions in these primate genomes, involving over 300 Mb of DNA and 1978 human genes. Accurately annotating these regions in the genome references has immediate applications for evolutionary and biomedical studies on primates. © 2018 Catacchio et al.; Published by Cold Spring Harbor Laboratory Press.

A road for a promising future for China's primates: The potential for restoration.

Science.gov (United States)

Chapman, Colin A

2018-07-18

China is one of the most dynamic countries of the world and it shelters some amazing levels of biodiversity, including some very special primate species. However, primarily as a result of forest loss, most of which occurred in historical times, approximately 70% of China's primate species have less than 3 000 individuals. Here I evaluate one road for future conservation/development that could produce very positive gains for China's primates; namely forest restoration. I argue that for a large scale restoration project to be possible two conditions must be met; the right societal conditions must exist and the right knowledge must be in hand. This evaluation suggests that the restoration of native forest to support many of China's primates holds great potential to advance conservation goals and to promote primate population recovery.

Human quadrupeds, primate quadrupedalism, and Uner Tan Syndrome.

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Liza J Shapiro

Full Text Available Since 2005, an extensive literature documents individuals from several families afflicted with "Uner Tan Syndrome (UTS," a condition that in its most extreme form is characterized by cerebellar hypoplasia, loss of balance and coordination, impaired cognitive abilities, and habitual quadrupedal gait on hands and feet. Some researchers have interpreted habitual use of quadrupedalism by these individuals from an evolutionary perspective, suggesting that it represents an atavistic expression of our quadrupedal primate ancestry or "devolution." In support of this idea, individuals with "UTS" are said to use diagonal sequence quadrupedalism, a type of quadrupedal gait that distinguishes primates from most other mammals. Although the use of primate-like quadrupedal gait in humans would not be sufficient to support the conclusion of evolutionary "reversal," no quantitative gait analyses were presented to support this claim. Using standard gait analysis of 518 quadrupedal strides from video sequences of individuals with "UTS", we found that these humans almost exclusively used lateral sequence-not diagonal sequence-quadrupedal gaits. The quadrupedal gait of these individuals has therefore been erroneously described as primate-like, further weakening the "devolution" hypothesis. In fact, the quadrupedalism exhibited by individuals with UTS resembles that of healthy adult humans asked to walk quadrupedally in an experimental setting. We conclude that quadrupedalism in healthy adults or those with a physical disability can be explained using biomechanical principles rather than evolutionary assumptions.

Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir.

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Avalos, Claudia R; Abreu, Celina M; Queen, Suzanne E; Li, Ming; Price, Sarah; Shirk, Erin N; Engle, Elizabeth L; Forsyth, Ellen; Bullock, Brandon T; Mac Gabhann, Feilim; Wietgrefe, Stephen W; Haase, Ashley T; Zink, M Christine; Mankowski, Joseph L; Clements, Janice E; Gama, Lucio

2017-08-15

A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir. Using a simian immunodeficiency virus (SIV)/macaque model for HIV encephalitis and AIDS, we evaluated whether infected cells persist in brain despite ART. Eight SIV-infected pig-tailed macaques were virally suppressed with ART, and plasma and CSF viremia levels were analyzed longitudinally. To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. Viral RNA in brain tissue of suppressed macaques was undetectable, although viral DNA was detected in all animals. The MΦ-QVOA demonstrated that the majority of suppressed animals contained latently infected BrMΦ. We also showed that virus produced in the MΦ-QVOAs was replication competent, suggesting that latently infected BrMΦ are capable of reestablishing productive infection upon treatment interruption. This report provides the first confirmation of the presence of replication-competent SIV in BrMΦ of ART-suppressed macaques and suggests that the highly debated issue of viral latency in macrophages, at least in brain, has been addressed in SIV-infected macaques treated with ART. IMPORTANCE Resting CD4 + T cells are currently the only cells that fit the definition of a latent reservoir. However, recent evidence suggests that HIV

Evidence for Conversion of Methanol to Formaldehyde in Nonhuman Primate Brain.

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Zhai, Rongwei; Zheng, Na; Rizak, Joshua; Hu, Xintian

2016-01-01

Many studies have reported that methanol toxicity to primates is mainly associated with its metabolites, formaldehyde (FA) and formic acid. While methanol metabolism and toxicology have been best studied in peripheral organs, little study has focused on the brain and no study has reported experimental evidence that demonstrates transformation of methanol into FA in the primate brain. In this study, three rhesus macaques were given a single intracerebroventricular injection of methanol to investigate whether a metabolic process of methanol to FA occurs in nonhuman primate brain. Levels of FA in cerebrospinal fluid (CSF) were then assessed at different time points. A significant increase of FA levels was found at the 18th hour following a methanol injection. Moreover, the FA level returned to a normal physiological level at the 30th hour after the injection. These findings provide direct evidence that methanol is oxidized to FA in nonhuman primate brain and that a portion of the FA generated is released out of the brain cells. This study suggests that FA is produced from methanol metabolic processes in the nonhuman primate brain and that FA may play a significant role in methanol neurotoxicology.

Vector-borne transmission of Trypanosoma cruzi among captive Neotropical primates in a Brazilian zoo.

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Minuzzi-Souza, Thaís Tâmara Castro; Nitz, Nadjar; Knox, Monique Britto; Reis, Filipe; Hagström, Luciana; Cuba, César A Cuba; Hecht, Mariana Machado; Gurgel-Gonçalves, Rodrigo

2016-01-26

Neotropical primates are important sylvatic hosts of Trypanosoma cruzi, the etiological agent of Chagas disease. Infection is often subclinical, but severe disease has been described in both free-ranging and captive primates. Panstrongylus megistus, a major T. cruzi vector, was found infesting a small-primate unit at Brasília zoo (ZooB), Brazil. ZooB lies close to a gallery-forest patch where T. cruzi circulates naturally. Here, we combine parasitological and molecular methods to investigate a focus of T. cruzi infection involving triatomine bugs and Neotropical primates at a zoo located in the Brazilian Savannah. We assessed T. cruzi infection in vectors using optical microscopy (n = 34) and nested PCR (n = 50). We used quantitative PCR (qPCR) to examine blood samples from 26 primates and necropsy samples from two primates that died during the study. We determined parasite lineages in five vectors and two primates by comparing glucose-6-phosphate isomerase (G6pi) gene sequences. Trypanosoma cruzi was found in 44 vectors and 17 primates (six genera and eight species); one Mico chrysoleucus and one Saguinus niger had high parasitaemias. Trypanosoma cruzi DNA was detected in three primates born to qPCR-negative mothers at ZooB and in the two dead specimens. One Callithrix geoffroyi became qPCR-positive over a two-year follow-up. All G6pi sequences matched T. cruzi lineage TcI. Our findings strongly suggest vector-borne T. cruzi transmission within a small-primate unit at ZooB - with vectors, and perhaps also parasites, presumably coming from nearby gallery forest. Periodic checks for vectors and parasites would help eliminate T. cruzi transmission foci in captive-animal facilities. This should be of special importance for captive-breeding programs involving endangered mammals, and would reduce the risk of accidental T. cruzi transmission to keepers and veterinarians.

Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.

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MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

2015-01-20

Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.

LOGISMOS-B for primates: primate cortical surface reconstruction and thickness measurement

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Oguz, Ipek; Styner, Martin; Sanchez, Mar; Shi, Yundi; Sonka, Milan

2015-03-01

Cortical thickness and surface area are important morphological measures with implications for many psychiatric and neurological conditions. Automated segmentation and reconstruction of the cortical surface from 3D MRI scans is challenging due to the variable anatomy of the cortex and its highly complex geometry. While many methods exist for this task in the context of the human brain, these methods are typically not readily applicable to the primate brain. We propose an innovative approach based on our recently proposed human cortical reconstruction algorithm, LOGISMOS-B, and the Laplace-based thickness measurement method. Quantitative evaluation of our approach was performed based on a dataset of T1- and T2-weighted MRI scans from 12-month-old macaques where labeling by our anatomical experts was used as independent standard. In this dataset, LOGISMOS-B has an average signed surface error of 0.01 +/- 0.03mm and an unsigned surface error of 0.42 +/- 0.03mm over the whole brain. Excluding the rather problematic temporal pole region further improves unsigned surface distance to 0.34 +/- 0.03mm. This high level of accuracy reached by our algorithm even in this challenging developmental dataset illustrates its robustness and its potential for primate brain studies.

Interspecies Transmission of Feline Immunodeficiency Virus from the Domestic Cat to the Tsushima Cat (Felis bengalensis euptilura) in the Wild

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Nishimura, Yoshiaki; Goto, Yuko; Yoneda, Kumiko; Endo, Yasuyuki; Mizuno, Takuya; Hamachi, Masaharu; Maruyama, Hiroyuki; Kinoshita, Hirotoshi; Koga, Susumu; Komori, Mitsuru; Fushuku, Seigo; Ushinohama, Kanji; Akuzawa, Masao; Watari, Toshihiro; Hasegawa, Atsuhiko; Tsujimoto, Hajime

1999-01-01

Feline immunodeficiency virus (FIV) was isolated from a wild-caught Tsushima cat (Felis bengalensis euptilura), an endangered Japanese nondomestic subspecies of leopard cat (F. bengalensis). Phylogenetic analysis of the env gene sequences indicated that the FIV from the Tsushima cat belonged to a cluster of subtype D FIVs from domestic cats. FIVs from both the Tsushima cat and the domestic cat showed similar levels of replication and cytopathicity in lymphoid cell lines derived from these two species. The results indicated the occurrence of interspecies transmission of FIV from the domestic cat to the Tsushima cat in the wild. PMID:10438892

Multiple Restrictions of Human Immunodeficiency Virus Type 1 in Feline Cells▿

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Münk, Carsten; Zielonka, Jörg; Constabel, Hannelore; Kloke, Björn-Philipp; Rengstl, Benjamin; Battenberg, Marion; Bonci, Francesca; Pistello, Mauro; Löchelt, Martin; Cichutek, Klaus

2007-01-01

The productive replication of human immunodeficiency virus type 1 (HIV-1) occurs exclusively in defined cells of human or chimpanzee origin, explaining why heterologous animal models for HIV replication, pathogenesis, vaccination, and therapy are not available. This lack of an animal model for HIV-1 studies prompted us to examine the susceptibility of feline cells in order to evaluate the cat (Felis catus) as an animal model for studying HIV-1. Here, we report that feline cell lines harbor multiple restrictions with respect to HIV-1 replication. The feline CD4 receptor does not permit virus infection. Feline T-cell lines MYA-1 and FeT-1C showed postentry restrictions resulting in low HIV-1 luciferase reporter activity and low expression of viral Gag-Pol proteins when pseudotyped vectors were used. Feline fibroblastic CrFK and KE-R cells, expressing human CD4 and CCR5, were very permissive for viral entry and HIV-long terminal repeat-driven expression but failed to support spreading infection. KE-R cells displayed a profound block with respect to release of HIV-1 particles. In contrast, CrFK cells allowed very efficient particle production; however, the CrFK cell-derived HIV-1 particles had low specific infectivity. We subsequently identified feline apolipoprotein B-editing catalytic polypeptide 3 (feAPOBEC3) proteins as active inhibitors of HIV-1 particle infectivity. CrFK cells express at least three different APOBEC3s: APOBEC3C, APOBEC3H, and APOBEC3CH. While the feAPOBEC3C did not significantly inhibit HIV-1, the feAPOBEC3H and feAPOBEC3CH induced G to A hypermutations of the viral cDNA and reduced the infectivity ∼10- to ∼40-fold. PMID:17459941

[Ecotourism disturbances to non-human primates].

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Fan, Peng-Lai; Xiang, Zuo-Fu

2013-02-01

In tandem with economic growth and rising living conditions, ecotourism has increasingly gained popularity among the Chinese public. Non-human primates, as charismatic animals and the closest relatives of human beings, have shown a strong affinity in attracting the general public and raising money, and for that reason a variety of monkey parks, valleys, and islands are becoming increasingly popular in China. Though successful in raising a substantial sum of money for the managing agency of a nature reserve, there may be negative impacts on monkey groups used in ecotourism. Here, to establish effective guards for non-human primates involved in ecotourism, we present a review on tourism disturbance and summarize the negative impacts on behavioral patterns, reproduction, and health condition of animals.

Does cortical bone thickness in the last sacral vertebra differ among tail types in primates?

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Nishimura, Abigail C; Russo, Gabrielle A

2017-04-01

The external morphology of the sacrum is demonstrably informative regarding tail type (i.e., tail presence/absence, length, and prehensility) in living and extinct primates. However, little research has focused on the relationship between tail type and internal sacral morphology, a potentially important source of functional information when fossil sacra are incomplete. Here, we determine if cortical bone cross-sectional thickness of the last sacral vertebral body differs among tail types in extant primates and can be used to reconstruct tail types in extinct primates. Cortical bone cross-sectional thickness in the last sacral vertebral body was measured from high-resolution CT scans belonging to 20 extant primate species (N = 72) assigned to tail type categories ("tailless," "nonprehensile short-tailed," "nonprehensile long-tailed," and "prehensile-tailed"). The extant dataset was then used to reconstruct the tail types for four extinct primate species. Tailless primates had significantly thinner cortical bone than tail-bearing primates. Nonprehensile short-tailed primates had significantly thinner cortical bone than nonprehensile long-tailed primates. Cortical bone cross-sectional thickness did not distinguish between prehensile-tailed and nonprehensile long-tailed taxa. Results are strongly influenced by phylogeny. Corroborating previous studies, Epipliopithecus vindobonensis was reconstructed as tailless, Archaeolemur edwardsi as long-tailed, Megaladapis grandidieri as nonprehensile short-tailed, and Palaeopropithecus kelyus as nonprehensile short-tailed or tailless. Results indicate that, in the context of phylogenetic clade, measures of cortical bone cross-sectional thickness can be used to allocate extinct primate species to tail type categories. © 2017 Wiley Periodicals, Inc.

Feline immunodeficiency virus in South America.

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Teixeira, Bruno M; Hagiwara, Mitika K; Cruz, Juliano C M; Hosie, Margaret J

2012-03-01

The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species). Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America.

Soils, time, and primate paleoenvironments

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Bown, T.M.; Kraus, M.J.

1993-01-01

Soils are the skin of the earth. From both poles to the equator, wherever rocks or sediment are exposed at the surface, soils are forming through the physical and chemical action of climate and living organisms. The physical attributes (color, texture, thickness) and chemical makeup of soils vary considerably, depending on the composition of the parent material and other variables: temperature, rainfall and soil moisture, vegetation, soil fauna, and the length of time that soil-forming processes have been at work. United States soil scientists1 have classified modern soils into ten major groups and numerous subgroups, each reflecting the composition and architecture of the soils and, to some extent, the processes that led to their formation. The physical and chemical processes of soil formation have been active throughout geologic time; the organic processes have been active at least since the Ordovician.2 Consequently, nearly all sedimentary rocks that were deposited in nonmarine settings and exposed to the elements contain a record of ancient, buried soils or paleosols. A sequence of these rocks, such as most ancient fluvial (stream) deposits, provides a record of soil paleoenvironments through time. Paleosols are also repositories of the fossils of organisms (body fossils) and the traces of those organisms burrowing, food-seeking, and dwelling activities (ichnofossils). Indeed, most fossil primates are found in paleosols. Careful study of ancient soils gives new, valuable insights into the correct temporal reconstruction of the primate fossil record and the nature of primate paleoenvironments. ?? 1993 Wiley-Liss, Inc.

High prevalence of antibodies against hepatitis A virus among captive nonhuman primates.

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Sa-nguanmoo, Pattaratida; Thawornsuk, Nutchanart; Rianthavorn, Pornpimol; Sommanustweechai, Angkana; Ratanakorn, Parntep; Poovorawan, Yong

2010-04-01

Hepatitis A virus (HAV) can infect not only humans but also several other nonhuman primates. This study has been conducted to evaluate the comprehensive anti-HAV seroprevalence in captive nonhuman primate populations in Thailand. The prevalence of antibodies against HAV in 96 captive nonhuman primates of 11 species was evaluated by competitive enzyme immunoassay (EIA). HAV antibodies were found in 64.7% (11/17) of macaques, 85.7% (6/7) of langurs, 28.4% (10/35) of gibbons, and 94.6% (35/37) of orangutans. However, anti-HAV IgM was not found in any sera. These results indicate that the majority of captive nonhuman primates in Thailand were exposed to HAV. It is possible that some of the animals were infected prior to capture.

Advances in primate stable isotope ecology-Achievements and future prospects.

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Crowley, Brooke E; Reitsema, Laurie J; Oelze, Vicky M; Sponheimer, Matt

2016-10-01

Stable isotope biogeochemistry has been used to investigate foraging ecology in non-human primates for nearly 30 years. Whereas early studies focused on diet, more recently, isotopic analysis has been used to address a diversity of ecological questions ranging from niche partitioning to nutritional status to variability in life history traits. With this increasing array of applications, stable isotope analysis stands to make major contributions to our understanding of primate behavior and biology. Most notably, isotopic data provide novel insights into primate feeding behaviors that may not otherwise be detectable. This special issue brings together some of the recent advances in this relatively new field. In this introduction to the special issue, we review the state of isotopic applications in primatology and its origins and describe some developing methodological issues, including techniques for analyzing different tissue types, statistical approaches, and isotopic baselines. We then discuss the future directions we envision for the field of primate isotope ecology. Am. J. Primatol. 78:995-1003, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Pathogenicity and rapid growth kinetics of feline immunodeficiency virus are linked to 3' elements.

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Jesse Thompson

Full Text Available Chimeric viruses constructed between a highly pathogenic Feline Immunodeficiency Virus isolate (FIV-C36 and a less pathogenic but neurotropic strain (FIV-PPR have been used to map viral genetic determinants of in vivo pathogenicity. Chimeric virus FIV-PCenv, which contains FIV-C36 genome from the 3' region of pol to upstream of the 3'LTR on an FIV-PPR backbone, was previously shown to be replication-competent in vivo, inducing altered CD4(+ T-cell and neutrophil profiles intermediate between parental strains following a delay in viral replication during initial infection. Examination of FIV-PCenv proviral sequences recovered at week 11 post-infection revealed two changes compared to initial viral inoculum; the most significant being arginine to histidine in the integrase region of Pol at residue 813 (R813H. Pooled plasma from the initial in vivo study was used to inoculate a second cohort of cats to determine whether similar virulence and kinetics could be established following primary infection. Viral replication kinetics and immunocyte profiles were monitored in blood, bone marrow, and saliva over a one-year period. Passaged FIV-PCenv again displayed intermediate phenotype between parental strains, but unlike primary experiments, the onset of acute viremia was not delayed. CD4/8 alterations were noted in all groups of animals, though significant changes from controls were delayed in FIV-PPR infected animals compared to FIV-C36 and FIV-PCenv. In vivo passage of FIV-PCenv increased replication-competence relative to the initial molecularly-cloned chimera in association with one adaptive nucleotide change in the 5' end of the genome relative to primary tissue culture inoculum, while mutations in the 3' end of the genome were not detected. The results are consistent with the interpretation that 3' elements contribute to heightened virulence of FIV-C36, and that integrase residue 813 plays an important role in facilitating successful in vivo

Neurobiological roots of language in primate audition: common computational properties.

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Bornkessel-Schlesewsky, Ina; Schlesewsky, Matthias; Small, Steven L; Rauschecker, Josef P

2015-03-01

Here, we present a new perspective on an old question: how does the neurobiology of human language relate to brain systems in nonhuman primates? We argue that higher-order language combinatorics, including sentence and discourse processing, can be situated in a unified, cross-species dorsal-ventral streams architecture for higher auditory processing, and that the functions of the dorsal and ventral streams in higher-order language processing can be grounded in their respective computational properties in primate audition. This view challenges an assumption, common in the cognitive sciences, that a nonhuman primate model forms an inherently inadequate basis for modeling higher-level language functions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Macroevolutionary dynamics and historical biogeography of primate diversification inferred from a species supermatrix.

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Mark S Springer

Full Text Available Phylogenetic relationships, divergence times, and patterns of biogeographic descent among primate species are both complex and contentious. Here, we generate a robust molecular phylogeny for 70 primate genera and 367 primate species based on a concatenation of 69 nuclear gene segments and ten mitochondrial gene sequences, most of which were extracted from GenBank. Relaxed clock analyses of divergence times with 14 fossil-calibrated nodes suggest that living Primates last shared a common ancestor 71-63 Ma, and that divergences within both Strepsirrhini and Haplorhini are entirely post-Cretaceous. These results are consistent with the hypothesis that the Cretaceous-Paleogene mass extinction of non-avian dinosaurs played an important role in the diversification of placental mammals. Previous queries into primate historical biogeography have suggested Africa, Asia, Europe, or North America as the ancestral area of crown primates, but were based on methods that were coopted from phylogeny reconstruction. By contrast, we analyzed our molecular phylogeny with two methods that were developed explicitly for ancestral area reconstruction, and find support for the hypothesis that the most recent common ancestor of living Primates resided in Asia. Analyses of primate macroevolutionary dynamics provide support for a diversification rate increase in the late Miocene, possibly in response to elevated global mean temperatures, and are consistent with the fossil record. By contrast, diversification analyses failed to detect evidence for rate-shift changes near the Eocene-Oligocene boundary even though the fossil record provides clear evidence for a major turnover event ("Grande Coupure" at this time. Our results highlight the power and limitations of inferring diversification dynamics from molecular phylogenies, as well as the sensitivity of diversification analyses to different species concepts.

Dietary quality and encephalization in platyrrhine primates

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Allen, Kari L.; Kay, Richard F.

2012-01-01

The high energetic costs of building and maintaining large brains are thought to constrain encephalization. The ‘expensive-tissue hypothesis’ (ETH) proposes that primates (especially humans) overcame this constraint through reduction of another metabolically expensive tissue, the gastrointestinal tract. Small guts characterize animals specializing on easily digestible diets. Thus, the hypothesis may be tested via the relationship between brain size and diet quality. Platyrrhine primates present an interesting test case, as they are more variably encephalized than other extant primate clades (excluding Hominoidea). We find a high degree of phylogenetic signal in the data for diet quality, endocranial volume and body size. Controlling for phylogenetic effects, we find no significant correlation between relative diet quality and relative endocranial volume. Thus, diet quality fails to account for differences in platyrrhine encephalization. One taxon, in particular, Brachyteles, violates predictions made by ETH in having a large brain and low-quality diet. Dietary reconstructions of stem platyrrhines further indicate that a relatively high-quality diet was probably in place prior to increases in encephalization. Therefore, it is unlikely that a shift in diet quality was a primary constraint release for encephalization in platyrrhines and, by extrapolation, humans. PMID:21831898

Dietary quality and encephalization in platyrrhine primates.

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Allen, Kari L; Kay, Richard F

2012-02-22

The high energetic costs of building and maintaining large brains are thought to constrain encephalization. The 'expensive-tissue hypothesis' (ETH) proposes that primates (especially humans) overcame this constraint through reduction of another metabolically expensive tissue, the gastrointestinal tract. Small guts characterize animals specializing on easily digestible diets. Thus, the hypothesis may be tested via the relationship between brain size and diet quality. Platyrrhine primates present an interesting test case, as they are more variably encephalized than other extant primate clades (excluding Hominoidea). We find a high degree of phylogenetic signal in the data for diet quality, endocranial volume and body size. Controlling for phylogenetic effects, we find no significant correlation between relative diet quality and relative endocranial volume. Thus, diet quality fails to account for differences in platyrrhine encephalization. One taxon, in particular, Brachyteles, violates predictions made by ETH in having a large brain and low-quality diet. Dietary reconstructions of stem platyrrhines further indicate that a relatively high-quality diet was probably in place prior to increases in encephalization. Therefore, it is unlikely that a shift in diet quality was a primary constraint release for encephalization in platyrrhines and, by extrapolation, humans.

In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject.

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Tsibris, Athe M N; Sagar, Manish; Gulick, Roy M; Su, Zhaohui; Hughes, Michael; Greaves, Wayne; Subramanian, Mani; Flexner, Charles; Giguel, Françoise; Leopold, Kay E; Coakley, Eoin; Kuritzkes, Daniel R

2008-08-01

Little is known about the in vivo development of resistance to human immunodeficiency virus type 1 (HIV-1) CCR5 antagonists. We studied 29 subjects with virologic failure from a phase IIb study of the CCR5 antagonist vicriviroc (VCV) and identified one individual with HIV-1 subtype C who developed VCV resistance. Studies with chimeric envelopes demonstrated that changes within the V3 loop were sufficient to confer VCV resistance. Resistant virus showed VCV-enhanced replication, cross-resistance to another CCR5 antagonist, TAK779, and increased sensitivity to aminooxypentane-RANTES and the CCR5 monoclonal antibody HGS004. Pretreatment V3 loop sequences reemerged following VCV discontinuation, implying that VCV resistance has associated fitness costs.

Distributional Replication

OpenAIRE

Beare, Brendan K.

2009-01-01

Suppose that X and Y are random variables. We define a replicating function to be a function f such that f(X) and Y have the same distribution. In general, the set of replicating functions for a given pair of random variables may be infinite. Suppose we have some objective function, or cost function, defined over the set of replicating functions, and we seek to estimate the replicating function with the lowest cost. We develop an approach to estimating the cheapest replicating function that i...

The evolution of vertical climbing in primates: evidence from reaction forces.

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Hanna, Jandy B; Granatosky, Michael C; Rana, Pooja; Schmitt, Daniel

2017-09-01

Vertical climbing is an essential behavior for arboreal animals, yet limb mechanics during climbing are poorly understood and rarely compared with those observed during horizontal walking. Primates commonly engage in both arboreal walking and vertical climbing, and this makes them an ideal taxa in which to compare these locomotor forms. Additionally, primates exhibit unusual limb mechanics compared with most other quadrupeds, with weight distribution biased towards the hindlimbs, a pattern that is argued to have evolved in response to the challenges of arboreal walking. Here we test an alternative hypothesis that functional differentiation between the limbs evolved initially as a response to climbing. Eight primate species were recorded locomoting on instrumented vertical and horizontal simulated arboreal runways. Forces along the axis of, and normal to, the support were recorded. During walking, all primates displayed forelimbs that were net braking, and hindlimbs that were net propulsive. In contrast, both limbs served a propulsive role during climbing. In all species, except the lorisids, the hindlimbs produced greater propulsive forces than the forelimbs during climbing. During climbing, the hindlimbs tends to support compressive loads, while the forelimb forces tend to be primarily tensile. This functional disparity appears to be body-size dependent. The tensile loading of the forelimbs versus the compressive loading of the hindlimbs observed during climbing may have important evolutionary implications for primates, and it may be the case that hindlimb-biased weight support exhibited during quadrupedal walking in primates may be derived from their basal condition of climbing thin branches. © 2017. Published by The Company of Biologists Ltd.

Behavioral and brain asymmetries in primates: a preliminary evaluation of two evolutionary hypotheses.

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Hopkins, William D; Misiura, Maria; Pope, Sarah M; Latash, Elitaveta M

2015-11-01

Contrary to many historical views, recent evidence suggests that species-level behavioral and brain asymmetries are evident in nonhuman species. Here, we briefly present evidence of behavioral, perceptual, cognitive, functional, and neuroanatomical asymmetries in nonhuman primates. In addition, we describe two historical accounts of the evolutionary origins of hemispheric specialization and present data from nonhuman primates that address these specific theories. Specifically, we first discuss the evidence that genes play specific roles in determining left-right differences in anatomical and functional asymmetries in primates. We next consider and present data on the hypothesis that hemispheric specialization evolved as a by-product of increasing brain size relative to the surface area of the corpus callosum in different primate species. Last, we discuss some of the challenges in the study of hemispheric specialization in primates and offer some suggestions on how to advance the field. © 2015 New York Academy of Sciences.

Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques.

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Carroll, Timothy; Lo, Ming; Lanteri, Marion; Dutra, Joseph; Zarbock, Katie; Silveira, Paola; Rourke, Tracy; Ma, Zhong-Min; Fritts, Linda; O'Connor, Shelby; Busch, Michael; Miller, Christopher J

2017-07-01

Zika virus (ZIKV) is a mosquito-transmitted virus that can cause severe defects in an infected fetus. ZIKV is also transmitted by sexual contact, although the relative importance of sexual transmission is unclear. To better understand the role of sexual transmission in ZIKV pathogenesis, a nonhuman primate (NHP) model of vaginal transmission was developed. ZIKV was readily transmitted to mature cycling female rhesus macaque (RM) by vaginal inoculation with 104-106 plaque-forming units (PFU). However, there was variability in susceptibility between the individual RM with 1->8 vaginal inoculations required to establish infection. After treatment with Depoprovera, a widely used contraceptive progestin, two RM that initially resisted 8 vaginal ZIKV inoculations became infected after one ZIKV inoculation. Thus, Depoprovera seemed to enhance susceptibility to vaginal ZIKV transmission. Unexpectedly, the kinetics of virus replication and dissemination after intravaginal ZIKV inoculation were markedly different from RM infected with ZIKV by subcutaneous (SQ) virus inoculation. Several groups have reported that after SQ ZIKV inoculation vRNA is rapidly detected in blood plasma with vRNA less common in urine and saliva and only rarely detected in female reproductive tract (FRT) secretions. In contrast, in vaginally inoculated RM, plasma vRNA is delayed for several days and ZIKV replication in, and vRNA shedding from, the FRT was found in all 6 animals. Further, after intravaginal transmission ZIKV RNA shedding from FRT secretions was detected before or simultaneously with plasma vRNA, and persisted for at least as long. Thus, ZIKV replication in the FRT was independent of, and often preceded virus replication in the tissues contributing to plasma vRNA. These results support the conclusion that ZIKV preferentially replicates in the FRT after vaginal transmission, but not after SQ transmission, and raise the possibility that there is enhanced fetal infection and pathology

Primate theory of mind: a state of the art review

DEFF Research Database (Denmark)

Byrnit, Jill

2006-01-01

-cognitive evner og siden Premack & Woodruff (1978) for første gang introducerede begrebet "theory of mind", er der blevet foretaget mange laboratorie-forsøg om mennesker og andre primaters evne til at attribuere mentale tilstande til andre. I nærværende artikel er størstedelen af disse forsøg med andre primater...

Chromatin Immunoprecipitation of Replication Factors Moving with the Replication Fork

OpenAIRE

Rapp, Jordan B.; Ansbach, Alison B.; Noguchi, Chiaki; Noguchi, Eishi

2009-01-01

Replication of chromosomes involves a variety of replication proteins including DNA polymerases, DNA helicases, and other accessory factors. Many of these proteins are known to localize at replication forks and travel with them as components of the replisome complex. Other proteins do not move with replication forks but still play an essential role in DNA replication. Therefore, in order to understand the mechanisms of DNA replication and its controls, it is important to examine localization ...

Primate-Specific Evolution of an LDLR Enhancer

Energy Technology Data Exchange (ETDEWEB)

Wang, Qian-fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles; Eisen, Michael B.; Cheng, Jan-Fang; Rubin,Edward M.; Boffelli, Dario

2006-06-28

Sequence changes in regulatory regions have often beeninvoked to explain phenotypic divergence among species, but molecularexamples of this have been difficult to obtain. In this study, weidentified an anthropoid primate specific sequence element thatcontributed to the regulatory evolution of the LDL receptor. Using acombination of close and distant species genomic sequence comparisonscoupled with in vivo and in vitro studies, we show that a functionalcholesterol-sensing sequence motif arose and was fixed within apre-existing enhancer in the common ancestor of anthropoid primates. Ourstudy demonstrates one molecular mechanism by which ancestral mammalianregulatory elements can evolve to perform new functions in the primatelineage leading to human.

Darwin's legacy and the study of primate visual communication.

Science.gov (United States)

de Waal, Frans B M

2003-12-01

After Charles Darwin's The Expression of the Emotions in Man and Animals, published in 1872, we had to wait 60 years before the theme of animal expressions was picked up by another astute observer. In 1935, Nadezhda Ladygina-Kohts published a detailed comparison of the expressive behavior of a juvenile chimpanzee and of her own child. After Kohts, we had to wait until the 1960s for modern ethological analyses of primate facial and gestural communication. Again, the focus was on the chimpanzee, but ethograms on other primates appeared as well. Our understanding of the range of expressions in other primates is at present far more advanced than that in Darwin's time. A strong social component has been added: instead of focusing on the expressions per se, they are now often classified according to the social situations in which they typically occur. Initially, quantitative analyses were sequential (i.e., concerned with temporal associations between behavior patterns), and they avoided the language of emotions. I will discuss some of this early work, including my own on the communicative repertoire of the bonobo, a close relative of the chimpanzee (and ourselves). I will provide concrete examples to make the point that there is a much richer matrix of contexts possible than the common behavioral categories of aggression, sex, fear, play, and so on. Primate signaling is a form of negotiation, and previous classifications have ignored the specifics of what animals try to achieve with their exchanges. There is also increasing evidence for signal conventionalization in primates, especially the apes, in both captivity and the field. This process results in group-specific or "cultural" communication patterns.

Human immunodeficiency virus type 1 KK26-27 matrix mutants display impaired infectivity, circularization and integration but not nuclear import

International Nuclear Information System (INIS)

Mannioui, Abdelkrim; Nelson, Elisabeth; Schiffer, Cecile

2005-01-01

We analyzed the role of human immunodeficiency virus (HIV)-1 matrix protein (MA) during the virus replication afferent phase. Single-round infection of H9 T lymphocytes showed that the combined mutation of MA Lys residues 26-27 in MA reported nuclear localization signal (NLS)-1 [Haffar, O.K., Popov, S., Dubrovsky, L., Agostini, I., Tang, H., Pushkarsky, T., Nadler, S.G., Bukrinsky, M., 2000. Two nuclear localization signals in the HIV-1 matrix protein regulate nuclear import of the HIV-1 pre-integration complex. J. Mol. Biol. 299 (2): 359-368] impaired infectivity, abrogated 2-LTR-circle formation and significantly reduced integration. However, the mutation did not affect viral DNA docking to chromatin in either interphasic or mitotic cells, indicating that MA N-terminal basic domain should not represent a major determinant of HIV-1 nuclear import in T lymphocytes. These data point to a previously unreported role of MA in the late, post-chromatin-binding, afferent phase of HIV-1 replication cycle

Biology of primate relaxin: A paracrine signal in early pregnancy?

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Hayes Eric S

2004-06-01

Full Text Available Abstract Relaxin is a peptide hormone that exerts numerous effects in a variety of tissues across a broad range of species. Although first identified more than 75 years ago interest in relaxin biology has waxed and waned over the years consistent with peaks and troughs of new experimental data on its wide-ranging biological effects and advances in relaxin enabling technologies. Recent insights into species-dependent differences in relaxin biology during pregnancy have once again stimulated a relative surge of interest in the study of relaxin's reproductive biology. Identification and pharmacological characterization of orphaned relaxin receptors and exploration of its paracrine effects on pregnancy using genomic and proteomic technologies have succeeded in fueling current interest in relaxin research. Primates and non-primate vertebrates exhibit very disparate profiles of relaxin genomics, proteomics and functional biology. Non-human primates appear to exhibit a very close similarity to humans with respect to relaxin reproductive biology but the similarities and subtle differences are only just beginning to be understood. We, and others, have shown that relaxin produces significant changes to the non-human primate endometrium during the peri-implantation period that are consistent with relaxin's long perceived role as a paracrine modulator of pregnancy. The purpose of this review is to summarize the reproductive biology of relaxin in non-human primates with a specific emphasis on the paracrine role of ovarian and endometrial relaxin during embryo implantation and early pregnancy.

Replication Catastrophe

DEFF Research Database (Denmark)

Toledo, Luis; Neelsen, Kai John; Lukas, Jiri

2017-01-01

Proliferating cells rely on the so-called DNA replication checkpoint to ensure orderly completion of genome duplication, and its malfunction may lead to catastrophic genome disruption, including unscheduled firing of replication origins, stalling and collapse of replication forks, massive DNA...... breakage, and, ultimately, cell death. Despite many years of intensive research into the molecular underpinnings of the eukaryotic replication checkpoint, the mechanisms underlying the dismal consequences of its failure remain enigmatic. A recent development offers a unifying model in which the replication...... checkpoint guards against global exhaustion of rate-limiting replication regulators. Here we discuss how such a mechanism can prevent catastrophic genome disruption and suggest how to harness this knowledge to advance therapeutic strategies to eliminate cancer cells that inherently proliferate under...

Primate Primordial Germ Cells Acquire Transplantation Potential by Carnegie Stage 23.

Science.gov (United States)

Clark, Amander T; Gkountela, Sofia; Chen, Di; Liu, Wanlu; Sosa, Enrique; Sukhwani, Meena; Hennebold, Jon D; Orwig, Kyle E

2017-07-11

Primordial germ cells (PGCs) are the earliest embryonic progenitors in the germline. Correct formation of PGCs is critical to reproductive health as an adult. Recent work has shown that primate PGCs can be differentiated from pluripotent stem cells; however, a bioassay that supports their identity as transplantable germ cells has not been reported. Here, we adopted a xenotransplantation assay by transplanting single-cell suspensions of human and nonhuman primate embryonic Macaca mulatta (rhesus macaque) testes containing PGCs into the seminiferous tubules of adult busulfan-treated nude mice. We discovered that both human and nonhuman primate embryonic testis are xenotransplantable, generating colonies while not generating tumors. Taken together, this work provides two critical references (molecular and functional) for defining transplantable primate PGCs. These results provide a blueprint for differentiating pluripotent stem cells to transplantable PGC-like cells in a species that is amenable to transplantation and fertility studies. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The Role of Faith-Based Organizations in the Education, Support, and Services for Persons Living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome.

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Stephens, Teresa M

2018-03-01

Faith-based organizations are in a unique position to provide resilience-enhancing efforts for persons living with human immunodeficiency virus/AIDS. Many persons living with human immunodeficiency virus/AIDS report having a strong faith or religious affiliation, with a large percentage attending church services on a regular basis. Faith-based organizations can use these factors to reach out to these individuals and effectively promote health, well-being, education, and support. Faith-based organizations can contribute to the reduction of stigma and isolation for persons living with human immunodeficiency virus/AIDS. Copyright © 2017 Elsevier Inc. All rights reserved.

Tracking blue cone signals in the primate brain.

Science.gov (United States)

Jayakumar, Jaikishan; Dreher, Bogdan; Vidyasagar, Trichur R

2013-05-01

In this paper, we review the path taken by signals originating from the short wavelength sensitive cones (S-cones) in Old World and New World primates. Two types of retinal ganglion cells (RGCs) carrying S-cone signals (blue-On and blue-Off cells) project to the dorsal lateral geniculate nucleus (dLGN) in the thalamus. In all primates, these S-cone signals are relayed through the 'dust-like' (konis in classical Greek) dLGN cells. In New World primates such as common marmoset, these very small cells are known to form distinct and spatially extensive, koniocellular layers. Although in Old World primates, such as macaques, koniocellular layers tend to be very thin, the adjacent parvocellular layers contain distinct koniocellular extensions. It appears that all S-cone signals are relayed through such konio cells, whether they are in the main koniocellular layers or in their colonies within the parvocellular layers of the dLGN. In the primary visual cortex, these signals begin to merge with the signals carried by the other two principal parallel channels, namely the magnocellular and parvocellular channels. This article will also review the possible routes taken by the S-cone signals to reach one of the topographically organised extrastriate visual cortical areas, the middle temporal area (area MT). This area is the major conduit for signals reaching the parietal cortex. Alternative visual inputs to area MT not relayed via the primary visual cortex area (V1) may provide the neurological basis for the phenomenon of 'blindsight' observed in human and non-human primates, who have partial or complete damage to the primary visual cortex. Short wavelength sensitive cone (S-cone) signals to area MT may also play a role in directing visual attention with possible implications for understanding the pathology in dyslexia and some of its treatment options. © 2012 The Authors. Clinical and Experimental Optometry © 2012 Optometrists Association Australia.

78 FR 11521 - Control of Communicable Disease; Foreign-Requirements for Importers of Nonhuman Primates (NHP)

Science.gov (United States)

2013-02-15

... Part 71 Control of Communicable Disease; Foreign--Requirements for Importers of Nonhuman Primates (NHP... Primates (NHP) AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human... live nonhuman primates (NHPs) by extending existing requirements for the importation of Macaca...

Database Replication Prototype

OpenAIRE

Vandewall, R.

2000-01-01

This report describes the design of a Replication Framework that facilitates the implementation and com-parison of database replication techniques. Furthermore, it discusses the implementation of a Database Replication Prototype and compares the performance measurements of two replication techniques based on the Atomic Broadcast communication primitive: pessimistic active replication and optimistic active replication. The main contributions of this report can be split into four parts....

Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates

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Angiolo Pierantoni

Full Text Available Respiratory Syncytial Virus (RSV is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV and Modified Vaccinia Ankara RSV (MVA-RSV encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Because RSV infection is restricted to the respiratory tract, we compared intranasal (IN and intramuscular (M administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower respiratory tract infection in the absence of detectable neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal IgA against the F protein. In conclusion, we have shown that our vectored RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing.

A new conservation strategy for China-A model starting with primates.

Science.gov (United States)

Pan, Ruliang; Oxnard, Charles; Grueter, Cyril C; Li, Baoguo; Qi, Xiaoguang; He, Gang; Guo, Songtao; Garber, Paul A

2016-11-01

Although the evolutionary history of primates in China dates to the Eocene, and includes major radiations of lorisids, hominoids, cercopithecines, and colobines during the Miocene, Pliocene, and Pleistocene, extensive human-induced habitat change and deforestation over the past few centuries has resulted in 22 of 25 extant species listed as threatened or endangered, and two species of gibbons extirpated in the last few years. This commentary briefly reviews factors that have contributed to the decline of primates in China over the past 400 years, and in particular how major social events and economic development in modern China have resulted in unsustainable environmental change. In response, we describe our efforts to develop a strategic scientific, educational and conservation partnership in China, focusing on primates, in which GIS technology will be used to integrate geographical profiles, climatic information, and changes in land use patterns and human and nonhuman primate distributions to highlight issues of immediate concern and to develop priority-based conservation solutions. Our goal is to evaluate how human-induced environmental change has impacted primates over time and to predict the likelihood of primate population extinctions in the near future. This model represents an early warning system that will be widely available to the Chinese government, public, educational institutions, researchers, and NGOs through social media and educational videos in order to arouse public awareness and promote wildlife conservation. We encourage colleagues across a broad range of academic disciplines, political ideologies, and the public to help move this strategy into reality, the sooner the better. Am. J. Primatol. 78:1137-1148, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Recurrent Infections May Signal Immunodeficiencies

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American Academy of Allergy Asthma & Immunology Menu Search Main navigation Skip to content Conditions & Treatments Allergies Asthma Primary Immunodeficiency Disease Related Conditions Drug Guide Conditions Dictionary Just ...

Effects of the distribution of female primates on the number of males.

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Laurel Mariah Carnes

Full Text Available The spatiotemporal distribution of females is thought to drive variation in mating systems, and hence plays a central role in understanding animal behavior, ecology and evolution. Previous research has focused on investigating the links between female spatiotemporal distribution and the number of males in haplorhine primates. However, important questions remain concerning the importance of spatial cohesion, the generality of the pattern across haplorhine and strepsirrhine primates, and the consistency of previous findings given phylogenetic uncertainty. To address these issues, we examined how the spatiotemporal distribution of females influences the number of males in primate groups using an expanded comparative dataset and recent advances in bayesian phylogenetic and statistical methods. Specifically, we investigated the effect of female distributional factors (female number, spatial cohesion, estrous synchrony, breeding season duration and breeding seasonality on the number of males in primate groups. Using bayesian approaches to control for uncertainty in phylogeny and the model of trait evolution, we found that the number of females exerted a strong influence on the number of males in primate groups. In a multiple regression model that controlled for female number, we found support for temporal effects, particularly involving female estrous synchrony: the number of males increases when females are more synchronously receptive. Similarly, the number of males increases in species with shorter birth seasons, suggesting that greater breeding seasonality makes defense of females more difficult for male primates. When comparing primate suborders, we found only weak evidence for differences in traits between haplorhines and strepsirrhines, and including suborder in the statistical models did not affect our conclusions or give compelling evidence for different effects in haplorhines and strepsirrhines. Collectively, these results demonstrate that

Neurologic manifestations of human immunodeficiency virus infection in children

NARCIS (Netherlands)

Epstein, L. G.; Sharer, L. R.; Oleske, J. M.; Connor, E. M.; Goudsmit, J.; Bagdon, L.; Robert-Guroff, M.; Koenigsberger, M. R.

1986-01-01

This report describes the neurologic manifestations of 36 children with human immunodeficiency virus (HIV) infection. In this cohort, in 16 of 21 children with acquired immunodeficiency syndrome (AIDS), three of 12 children with AIDS-related complex, and one of three asymptomatic seropositive

Birth seasonality and offspring production in threatened neotropical primates related to climate

Science.gov (United States)

Wiederholt, R.; Post, E.

2011-01-01

Given the threatened status of many primate species, the impacts of global warming on primate reproduction and, consequently, population growth should be of concern. We examined relations between climatic variability and birth seasonality, offspring production, and infant sex ratios in two ateline primates, northern muriquis, and woolly monkeys. In both species, the annual birth season was delayed by dry conditions and El Ni??o years, and delayed birth seasons were linked to lower birth rates. Additionally, increased mean annual temperatures were associated with lower birth rates for northern muriquis. Offspring sex ratios varied with climatic conditions in both species, but in different ways: directly in woolly monkeys and indirectly in northern muriquis. Woolly monkeys displayed an increase in the proportion of males among offspring in association with El Ni??o events, whereas in northern muriquis, increases in the proportion of males among offspring were associated with delayed onset of the birth season, which itself was related, although weakly, to warm, dry conditions. These results illustrate that global warming, increased drought frequency, and changes in the frequency of El Ni??o events could limit primate reproductive output, threatening the persistence and recovery of ateline primate populations. ?? 2011 Blackwell Publishing Ltd.

Theories about evolutionary origins of human hepatitis B virus in primates and humans.

Science.gov (United States)

Souza, Breno Frederico de Carvalho Dominguez; Drexler, Jan Felix; Lima, Renato Santos de; Rosário, Mila de Oliveira Hughes Veiga do; Netto, Eduardo Martins

2014-01-01

The human hepatitis B virus causes acute and chronic hepatitis and is considered one of the most serious human health issues by the World Health Organization, causing thousands of deaths per year. There are similar viruses belonging to the Hepadnaviridae family that infect non-human primates and other mammals as well as some birds. The majority of non-human primate virus isolates were phylogenetically close to the human hepatitis B virus, but like the human genotypes, the origins of these viruses remain controversial. However, there is a possibility that human hepatitis B virus originated in primates. Knowing whether these viruses might be common to humans and primates is crucial in order to reduce the risk to humans. To review the existing knowledge about the evolutionary origins of viruses of the Hepadnaviridae family in primates. This review was done by reading several articles that provide information about the Hepadnaviridae virus family in non-human primates and humans and the possible origins and evolution of these viruses. The evolutionary origin of viruses of the Hepadnaviridae family in primates has been dated back to several thousand years; however, recent analyses of genomic fossils of avihepadnaviruses integrated into the genomes of several avian species have suggested a much older origin of this genus. Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the '90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate

Feline Immunodeficiency Virus in South America

Directory of Open Access Journals (Sweden)

Bruno M. Teixeira

2012-03-01

Full Text Available The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species. Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV causes an immune system disease in domestic cats (Felis catus involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs in South America.

Induced Pluripotent Stem Cells from Nonhuman Primates.

Science.gov (United States)

Mishra, Anuja; Qiu, Zhifang; Farnsworth, Steven L; Hemmi, Jacob J; Li, Miao; Pickering, Alexander V; Hornsby, Peter J

2016-01-01

Induced pluripotent stem cells from nonhuman primates (NHPs) have unique roles in cell biology and regenerative medicine. Because of the relatedness of NHPs to humans, NHP iPS cells can serve as a source of differentiated derivatives that can be used to address important questions in the comparative biology of primates. Additionally, when used as a source of cells for regenerative medicine, NHP iPS cells serve an invaluable role in translational experiments in cell therapy. Reprogramming of NHP somatic cells requires the same conditions as previously established for human cells. However, throughout the process, a variety of modifications to the human cell protocols must be made to accommodate significant species differences.

Dental maturation, eruption, and gingival emergence in the upper jaw of newborn primates.

Science.gov (United States)

Smith, Timothy D; Muchlinski, Magdalena N; Jankord, Kathryn D; Progar, Abbigal J; Bonar, Christopher J; Evans, Sian; Williams, Lawrence; Vinyard, Christopher J; Deleon, Valerie B

2015-12-01

In this report we provide data on dental eruption and tooth germ maturation at birth in a large sample constituting the broadest array of non-human primates studied to date. Over 100 perinatal primates, obtained from natural captive deaths, were screened for characteristics indicating premature birth, and were subsequently studied using a combination of histology and micro-CT. Results reveal one probable unifying characteristic of living primates: relatively advanced maturation of deciduous teeth and M1 at birth. Beyond this, there is great diversity in the status of tooth eruption and maturation (dental stage) in the newborn primate. Contrasting strategies in producing a masticatory battery are already apparent at birth in strepsirrhines and anthropoids. Results show that dental maturation and eruption schedules are potentially independently co-opted as different strategies for attaining feeding independence. The most common strategy in strepsirrhines is accelerating eruption and the maturation of the permanent dentition, including replacement teeth. Anthropoids, with only few exceptions, accelerate mineralization of the deciduous teeth, while delaying development of all permanent teeth except M1. These results also show that no living primate resembles the altricial tree shrew (Tupaia) in dental development. Our preliminary observations suggest that ecological explanations, such as diet, provide an explanation for certain morphological variations at birth. These results confirm previous work on perinatal indriids indicating that these and other primates telegraph their feeding adaptations well before masticatory anatomy is functional. Quantitative analyses are required to decipher specific dietary and other influences on dental size and maturation in the newborn primate. © 2015 Wiley Periodicals, Inc.

Logging Activity Adversely Impacts Primate Diversity and Density in the Kwabre Rainforest of Ghana

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Emmanuel Danquah

2016-01-01

Full Text Available Knowledge on the impacts of logging activity on inhabitant primate species in Kwabre Rainforest, Ghana, is vital for the development of a comprehensive conservation and management plan. With this background, primate density and diversity were recorded along line transects in logged and unlogged areas (strata to assess the impact of logging activity on these parameters. Six distinct primate species were confirmed including Roloway monkey (Cercopithecus roloway, listed as endangered in the IUCN List of Threatened Species, white-naped mangabey (Cercocebus lunulatus, vulnerable, and Geoffroy’s black-and-white colobus (Colobus vellerosus, vulnerable. There was a significant difference (Mann-Whitney U test: U=36.0, p<0.01 in primate encounter rates between the logged and unlogged strata with higher species diversity in unlogged stratum (H=2.91 compared to the logged stratum (H=1.44. Regression analysis indicated a significant effect (r2=0.945, p<0.01 of logging on primate encounter rates. Our results suggest that logging activity can alter composition of primate communities. One option to forestall further forest degradation and its adverse effects on primates would be to grant the Kwabre Rainforest protected area status under Ghanaian law and manage it under an integrated conservation plan that includes neighbouring Ankasa Conservation Area in Ghana and Tanoé Forest in Cote d’Ivoire.

Functional morphology of the primate head and neck.

Science.gov (United States)

Nalley, Thierra K; Grider-Potter, Neysa

2015-04-01

The vertebral column plays a key role in maintaining posture, locomotion, and transmitting loads between body components. Cervical vertebrae act as a bridge between the torso and head and play a crucial role in the maintenance of head position and the visual field. Despite its importance in positional behaviors, the functional morphology of the cervical region remains poorly understood, particularly in comparison to the thoracic and lumbar sections of the spinal column. This study tests whether morphological variation in the primate cervical vertebrae correlates with differences in postural behavior. Phylogenetic generalized least-squares analyses were performed on a taxonomically broad sample of 26 extant primate taxa to test the link between vertebral morphology and posture. Kinematic data on primate head and neck postures were used instead of behavioral categories in an effort to provide a more direct analysis of our functional hypothesis. Results provide evidence for a function-form link between cervical vertebral shape and postural behaviors. Specifically, taxa with more pronograde heads and necks and less kyphotic orbits exhibit cervical vertebrae with longer spinous processes, indicating increased mechanical advantage for deep nuchal musculature, and craniocaudally longer vertebral bodies and more coronally oriented zygapophyseal articular facets, suggesting an emphasis on curve formation and maintenance within the cervical lordosis, coupled with a greater resistance to translation and ventral displacement. These results not only document support for functional relationships in cervical vertebrae features across a wide range of primate taxa, but highlight the utility of quantitative behavioral data in functional investigations. © 2015 Wiley Periodicals, Inc.

Emotions, stress, and maternal motivation in primates.

Science.gov (United States)

Maestripieri, Dario

2011-06-01

Recent research conducted with nonhuman primates confirms that adaptive emotional processes, such as maternal attraction arousability and maternal anxiety arousability, enhance and sustain female motivation to interact with infants, invest in them, and protect them during the postpartum period. Changes in these emotional processes, and concomitant changes in maternal motivation, facilitate the reduction and eventual termination of maternal investment associated with infant weaning. Although laboratory studies of rodents and socially deprived rhesus monkeys have suggested that nulliparous females are neophobic and find infant stimuli aversive, recent primate research indicates that neophobia or aversion to infant stimuli do not occur in females with normal developmental experience. Furthermore, although some rodent and human studies have shown that lactation is accompanied by physiological hyporesponsiveness to stress, other studies of rodents, nonhuman primates, and humans indicate that mothers are highly vulnerable to stress and that stress-induced dysregulation of emotions can interfere with maternal motivation and parenting behavior. It is possible that some aspects of the emotional and experiential regulation of maternal motivation and parental behavior are different in different mammalian species. However, variation in the environments in which subjects are tested and in their developmental experience may also be responsible for the some discrepancies between the results of different studies. © 2010 Wiley-Liss, Inc.

The appropriation of glucose through primate neurodevelopment.

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Bauernfeind, Amy L; Babbitt, Courtney C

2014-12-01

The human brain is considerably larger and more energetically costly than that of other primate species. As such, discovering how human ancestors were able to provide sufficient energy to their brains is a central theme in the study of hominin evolution. However, many discussions of metabolism frequently omit the different ways in which energy, primarily glucose, is used once made available to the brain. In this review, we discuss two glucose metabolic pathways, oxidative phosphorylation and aerobic glycolysis, and their respective contributions to the energetic and anabolic budgets of the brain. While oxidative phosphorylation is a more efficient producer of energy, aerobic glycolysis contributes essential molecules for the growth of the brain and maintaining the structure of its cells. Although both pathways occur in the brain throughout the lifetime, aerobic glycolysis is a critical pathway during development, and oxidative phosphorylation is highest during adulthood. We outline how elevated levels of aerobic glycolysis may support the protracted neurodevelopmental sequence of humans compared with other primates. Finally, we review the genetic evidence for differences in metabolic function in the brains of primates and explore genes that may provide insight into how glucose metabolism may differ across species. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Use of Recombinant Feline Interferon Omega Therapy as an Immune-Modulator in Cats Naturally Infected with Feline Immunodeficiency Virus: New Perspectives

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Rodolfo Oliveira Leal

2016-10-01

Full Text Available Type I interferons (IFNs are well-known cytokines that, among their main functions, are key components of the host immune response against viral infections. Due to its immune modulation properties, they are commonly used in the therapeutic approach of various retroviral infections, namely human immunodeficiency virus (HIV and feline immunodeficiency virus (FIV. In HIV infection, it has been shown that IFN therapy limits early viral replication, particularly useful on post-exposure prophylaxis. In veterinary medicine, recombinant feline interferon omega (rFeIFN-ω was the first interferon licensed for use in cats. Several studies have recently shown that this compound seems to stimulate the innate immunity, decreasing clinical signs and co-infections in naturally FIV-infected cats. More than summarizing the main conclusions about rFeIFN-ω in cats, this review emphasizes the immune-modulation properties of IFN therapy, opening new perspectives for its use in retroviral infections. Either in FIV-infected cats or in HIV individuals, type I IFNs seem to induce an innate immune-modulation and should not be overlooked as a therapeutic option in retroviral infections.

The Use of Recombinant Feline Interferon Omega Therapy as an Immune-Modulator in Cats Naturally Infected with Feline Immunodeficiency Virus: New Perspectives.

Science.gov (United States)

Leal, Rodolfo Oliveira; Gil, Solange

2016-10-27

Type I interferons (IFNs) are well-known cytokines that, among their main functions, are key components of the host immune response against viral infections. Due to its immune modulation properties, they are commonly used in the therapeutic approach of various retroviral infections, namely human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV). In HIV infection, it has been shown that IFN therapy limits early viral replication, particularly useful on post-exposure prophylaxis. In veterinary medicine, recombinant feline interferon omega (rFeIFN-ω) was the first interferon licensed for use in cats. Several studies have recently shown that this compound seems to stimulate the innate immunity, decreasing clinical signs and co-infections in naturally FIV-infected cats. More than summarizing the main conclusions about rFeIFN-ω in cats, this review emphasizes the immune-modulation properties of IFN therapy, opening new perspectives for its use in retroviral infections. Either in FIV-infected cats or in HIV individuals, type I IFNs seem to induce an innate immune-modulation and should not be overlooked as a therapeutic option in retroviral infections.

Primate social attention: Species differences and effects of individual experience in humans, great apes, and macaques

OpenAIRE

Kano, Fumihiro; Shepherd, Stephen V.; Hirata, Satoshi; Call, Josep

2018-01-01

When viewing social scenes, humans and nonhuman primates focus on particular features, such as the models’ eyes, mouth, and action targets. Previous studies reported that such viewing patterns vary significantly across individuals in humans, and also across closely-related primate species. However, the nature of these individual and species differences remains unclear, particularly among nonhuman primates. In large samples of human and nonhuman primates, we examined species differences and th...

Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.

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Blaney, Joseph E; Marzi, Andrea; Willet, Mallory; Papaneri, Amy B; Wirblich, Christoph; Feldmann, Friederike; Holbrook, Michael; Jahrling, Peter; Feldmann, Heinz; Schnell, Matthias J

2013-01-01

We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies virus (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.

Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.

Directory of Open Access Journals (Sweden)

Joseph E Blaney

Full Text Available We have previously described the generation of a novel Ebola virus (EBOV vaccine platform based on (a replication-competent rabies virus (RABV, (b replication-deficient RABV, or (c chemically inactivated RABV expressing EBOV glycoprotein (GP. Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.

45 CFR 96.128 - Requirements regarding human immunodeficiency virus.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Requirements regarding human immunodeficiency virus. 96.128 Section 96.128 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... human immunodeficiency virus. (a) In the case of a designated State as described in paragraph (b) of...

Combining diffusion magnetic resonance tractography with stereology highlights increased cross-cortical integration in primates.

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Charvet, Christine J; Hof, Patrick R; Raghanti, Mary Ann; Van Der Kouwe, Andre J; Sherwood, Chet C; Takahashi, Emi

2017-04-01

The isocortex of primates is disproportionately expanded relative to many other mammals, yet little is known about what the expansion of the isocortex entails for differences in cellular composition and connectivity patterns in primates. Across the depth of the isocortex, neurons exhibit stereotypical patterns of projections. Upper-layer neurons (i.e., layers II-IV) project within and across cortical areas, whereas many lower-layer pyramidal neurons (i.e., layers V-VI) favor connections to subcortical regions. To identify evolutionary changes in connectivity patterns, we quantified upper (i.e., layers II-IV)- and lower (i.e., layers V-VI)-layer neuron numbers in primates and other mammals such as rodents and carnivores. We also used MR tractography based on high-angular resolution diffusion imaging and diffusion spectrum imaging to compare anterior-to-posterior corticocortical tracts between primates and other mammals. We found that primates possess disproportionately more upper-layer neurons as well as an expansion of anterior-to-posterior corticocortical tracts compared with other mammals. Taken together, these findings demonstrate that primates deviate from other mammals in exhibiting increased cross-cortical connectivity. J. Comp. Neurol. 525:1075-1093, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Poliovirus Excretion in Children with Primary Immunodeficiency Disorders, India.

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Mohanty, Madhu Chhanda; Madkaikar, Manisha Rajan; Desai, Mukesh; Taur, Prasad; Nalavade, Uma Prajwal; Sharma, Deepa Kailash; Gupta, Maya; Dalvi, Aparna; Shabrish, Snehal; Kulkarni, Manasi; Aluri, Jahnavi; Deshpande, Jagadish Mohanrao

2017-10-01

Prolonged excretion of poliovirus can occur in immunodeficient patients who receive oral polio vaccine, which may lead to propagation of highly divergent vaccine-derived polioviruses (VDPVs), posing a concern for global polio eradication. This study aimed to estimate the proportion of primary immunodeficient children with enterovirus infection and to identify the long-term polio/nonpolio enterovirus excreters in a tertiary care unit in Mumbai, India. During September 2014-April 2017, 151 patients received diagnoses of primary immunodeficiency (PID). We isolated 8 enteroviruses (3 polioviruses and 5 nonpolio enteroviruses) in cell culture of 105 fecal samples collected from 42 patients. Only 1 patient with severe combined immunodeficiency was identified as a long-term VDPV3 excreter (for 2 years after identification of infection). Our results show that the risk of enterovirus excretion among children in India with PID is low; however, systematic screening is necessary to identify long-term poliovirus excreters until the use of oral polio vaccine is stopped.

[Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II)].

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Toledano, A; Álvarez, M I; López-Rodríguez, A B; Toledano-Díaz, A; Fernández-Verdecia, C I

2014-01-01

In the ageing process there are some species of non-human primates which can show some of the defining characteristics of the Alzheimer's disease (AD) of man, both in neuropathological changes and cognitive-behavioural symptoms. The study of these species is of prime importance to understand AD and develop therapies to combat this neurodegenerative disease. In this second part of the study, these AD features are discussed in the most important non-experimental AD models (Mouse Lemur -Microcebus murinus, Caribbean vervet -Chlorocebus aethiops, and the Rhesus and stump-tailed macaque -Macaca mulatta and M. arctoides) and experimental models (lesional, neurotoxic, pharmacological, immunological, etc.) non-human primates. In all these models cerebral amyloid neuropathology can occur in senility, although with different levels of incidence (100% in vervets;primates, such as the macaque, the existence of a possible continuum between "normal" ageing process, "normal" ageing with no deep neuropathological and cognitive-behavioural changes, and "pathological ageing" (or "Alzheimer type ageing"), may be considered. In other cases, such as the Caribbean vervet, neuropathological changes are constant and quite marked, but its impact on cognition and behaviour does not seem to be very important. This does assume the possible existence in the human senile physiological regression of a stable phase without dementia even if neuropathological changes appeared. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

The Replication Recipe: What makes for a convincing replication?

NARCIS (Netherlands)

Brandt, M.J.; IJzerman, H.; Dijksterhuis, A.J.; Farach, F.J.; Geller, J.; Giner-Sorolla, R.; Grange, J.A.; Perugini, M.; Spies, J.R.; Veer, A. van 't

2014-01-01

Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed

The replication recipe : What makes for a convincing replication?

NARCIS (Netherlands)

Brandt, M.J.; IJzerman, H.; Dijksterhuis, Ap; Farach, Frank J.; Geller, Jason; Giner-Sorolla, Roger; Grange, James A.; Perugini, Marco; Spies, Jeffrey R.; van 't Veer, Anna

Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed

A small nonhuman primate model for filovirus-induced disease.

Science.gov (United States)

Carrion, Ricardo; Ro, Youngtae; Hoosien, Kareema; Ticer, Anysha; Brasky, Kathy; de la Garza, Melissa; Mansfield, Keith; Patterson, Jean L

2011-11-25

Ebolavirus and Marburgvirus are members of the filovirus family and induce a fatal hemorrhagic disease in humans and nonhuman primates with 90% case fatality. To develop a small nonhuman primate model for filovirus disease, common marmosets (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus Musoke or Ebolavirus Zaire. The infection resulted in a systemic fatal disease with clinical and morphological features closely resembling human infection. Animals experienced weight loss, fever, high virus titers in tissue, thrombocytopenia, neutrophilia, high liver transaminases and phosphatases and disseminated intravascular coagulation. Evidence of a severe disseminated viral infection characterized principally by multifocal to coalescing hepatic necrosis was seen in EBOV animals. MARV-infected animals displayed only moderate fibrin deposition in the spleen. Lymphoid necrosis and lymphocytic depletion observed in spleen. These findings provide support for the use of the common marmoset as a small nonhuman primate model for filovirus induced hemorrhagic fever. Copyright © 2011 Elsevier Inc. All rights reserved.

Curaxin CBL0100 Blocks HIV-1 Replication and Reactivation through Inhibition of Viral Transcriptional Elongation

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Maxime J. Jean

2017-10-01

Full Text Available Despite combination antiretroviral therapy (cART, acquired immunodeficiency syndrome (AIDS, predominantly caused by the human immunodeficiency virus type 1 (HIV-1, remains incurable. The barrier to a cure lies in the virus' ability to establish a latent infection in HIV/AIDS patients. Unsurprisingly, efforts for a sterilizing cure have focused on the “shock and kill” strategy using latency-reversing agents (LRAs to complement cART in order to eliminate these latent reservoirs. However, this method faces numerous challenges. Recently, the “block and lock” strategy has been proposed. It aims to reinforce a deep state of latency and prevent sporadic reactivation (“blip” of HIV-1 using latency-promoting agents (LPAs for a functional cure. Our studies of curaxin 100 (CBL0100, a small-molecule targeting the facilitates chromatin transcription (FACT complex, show that it blocks both HIV-1 replication and reactivation in in vitro and ex vivo models of HIV-1. Mechanistic investigation elucidated that CBL0100 preferentially targets HIV-1 transcriptional elongation and decreases the occupancy of RNA Polymerase II (Pol II and FACT at the HIV-1 promoter region. In conclusion, CBL0100 is a newly identified inhibitor of HIV-1 transcription that can be used as an LPA in the “block and lock” cure strategy.

Postsacral vertebral morphology in relation to tail length among primates and other mammals.

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Russo, Gabrielle A

2015-02-01

Tail reduction/loss independently evolved in a number of mammalian lineages, including hominoid primates. One prerequisite to appropriately contextualizing its occurrence and understanding its significance is the ability to track evolutionary changes in tail length throughout the fossil record. However, to date, the bony correlates of tail length variation among living taxa have not been comprehensively examined. This study quantifies postsacral vertebral morphology among living primates and other mammals known to differ in relative tail length (RTL). Linear and angular measurements with known biomechanical significance were collected on the first, mid-, and transition proximal postsacral vertebrae, and their relationship with RTL was assessed using phylogenetic generalized least-squares regression methods. Compared to shorter-tailed primates, longer-tailed primates possess a greater number of postsacral vertebral features associated with increased proximal tail flexibility (e.g., craniocaudally longer vertebral bodies), increased intervertebral body joint range of motion (e.g., more circularly shaped cranial articular surfaces), and increased leverage of tail musculature (e.g., longer spinous processes). These observations are corroborated by the comparative mammalian sample, which shows that distantly related short-tailed (e.g., Phascolarctos, Lynx) and long-tailed (e.g., Dendrolagus, Acinonyx) nonprimate mammals morphologically converge with short-tailed (e.g., Macaca tonkeana) and long-tailed (e.g., Macaca fascicularis) primates, respectively. Multivariate models demonstrate that the variables examined account for 70% (all mammals) to 94% (only primates) of the variance in RTL. Results of this study may be used to infer the tail lengths of extinct primates and other mammals, thereby improving our understanding about the evolution of tail reduction/loss. © 2014 Wiley Periodicals, Inc.

Response of frugivorous primates to changes in fruit supply in a northern Amazonian forest.

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Mourthé, I

2014-08-01

Few attempts have been made to understand how spatiotemporal changes in fruit supply influence frugivores in tropical forests. The marked spatiotemporal variation in fruit supply can affect frugivore abundance and distribution, but studies addressing the effects of this variation on primates are scarce. The present study aimed to investigate how the spatiotemporal distribution of fruits influences the local distribution of three frugivorous primates in the eastern part of the Maracá Ecological Station, a highly seasonal Amazonian rainforest. Specifically, it was hypothesised that primate distribution will track changes in fruit supply, resulting that sites with high fruit availability should be heavily used by primates. During a 1-year study, fruit supply (ground fruit surveys) and primate density (line-transects) were monitored in twelve 2 km-long transects at monthly intervals. Fruit supply varied seasonally, being low during the dry season. The density of Ateles belzebuth was positively related to fruit supply during fruit shortage, but Cebus olivaceus and Alouatta macconnelli did not follow the same pattern. The supply of Sapotaceae fruit was an important component determining local distribution of A. belzebuth during the overall fruit shortage. Highly frugivorous primates such as A. belzebuth respond to seasonal decline in fruit supply by congregating at places with high fruit supply in this forest, particularly, those with many individuals of species of Sapotaceae. This study underscores the importance of small-scale spatiotemporal changes of fruit supply as a key component of frugivorous primate ecology in highly seasonal environments.

The HIV-1 transcriptional activator Tat has potent nucleic acid chaperoning activities in vitro.

Science.gov (United States)

Kuciak, Monika; Gabus, Caroline; Ivanyi-Nagy, Roland; Semrad, Katharina; Storchak, Roman; Chaloin, Olivier; Muller, Sylviane; Mély, Yves; Darlix, Jean-Luc

2008-06-01

The human immunodeficiency virus type 1 (HIV-1) is a primate lentivirus that causes the acquired immunodeficiency syndrome (AIDS). In addition to the virion structural proteins and enzyme precursors, that are Gag, Env and Pol, HIV-1 encodes several regulatory proteins, notably a small nuclear transcriptional activator named Tat. The Tat protein is absolutely required for virus replication since it controls proviral DNA transcription to generate the full-length viral mRNA. Tat can also regulate mRNA capping and splicing and was recently found to interfere with the cellular mi- and siRNA machinery. Because of its extensive interplay with nucleic acids, and its basic and disordered nature we speculated that Tat had nucleic acid-chaperoning properties. This prompted us to examine in vitro the nucleic acid-chaperoning activities of Tat and Tat peptides made by chemical synthesis. Here we report that Tat has potent nucleic acid-chaperoning activities according to the standard DNA annealing, DNA and RNA strand exchange, RNA ribozyme cleavage and trans-splicing assays. The active Tat(44-61) peptide identified here corresponds to the smallest known sequence with DNA/RNA chaperoning properties.

Properties of virion transactivator proteins encoded by primate cytomegaloviruses

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Barry Peter A

2009-05-01

Full Text Available Abstract Background Human cytomegalovirus (HCMV is a betaherpesvirus that causes severe disease in situations where the immune system is immature or compromised. HCMV immediate early (IE gene expression is stimulated by the virion phosphoprotein pp71, encoded by open reading frame (ORF UL82, and this transactivation activity is important for the efficient initiation of viral replication. It is currently recognized that pp71 acts to overcome cellular intrinsic defences that otherwise block viral IE gene expression, and that interactions of pp71 with the cell proteins Daxx and ATRX are important for this function. A further property of pp71 is the ability to enable prolonged gene expression from quiescent herpes simplex virus type 1 (HSV-1 genomes. Non-human primate cytomegaloviruses encode homologs of pp71, but there is currently no published information that addresses their effects on gene expression and modes of action. Results The UL82 homolog encoded by simian cytomegalovirus (SCMV, strain Colburn, was identified and cloned. This ORF, named S82, was cloned into an HSV-1 vector, as were those from baboon, rhesus monkey and chimpanzee cytomegaloviruses. The use of an HSV-1 vector enabled expression of the UL82 homologs in a range of cell types, and permitted investigation of their abilities to direct prolonged gene expression from quiescent genomes. The results show that all UL82 homologs activate gene expression, and that neither host cell type nor promoter target sequence has major effects on these activities. Surprisingly, the UL82 proteins specified by non-human primate cytomegaloviruses, unlike pp71, did not direct long term expression from quiescent HSV-1 genomes. In addition, significant differences were observed in the intranuclear localization of the UL82 homologs, and in their effects on Daxx. Strikingly, S82 mediated the release of Daxx from nuclear domain 10 substructures much more rapidly than pp71 or the other proteins tested. All

Two Influential Primate Classifications Logically Aligned.

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Franz, Nico M; Pier, Naomi M; Reeder, Deeann M; Chen, Mingmin; Yu, Shizhuo; Kianmajd, Parisa; Bowers, Shawn; Ludäscher, Bertram

2016-07-01

Classifications and phylogenies of perceived natural entities change in the light of new evidence. Taxonomic changes, translated into Code-compliant names, frequently lead to name:meaning dissociations across succeeding treatments. Classification standards such as the Mammal Species of the World (MSW) may experience significant levels of taxonomic change from one edition to the next, with potential costs to long-term, large-scale information integration. This circumstance challenges the biodiversity and phylogenetic data communities to express taxonomic congruence and incongruence in ways that both humans and machines can process, that is, to logically represent taxonomic alignments across multiple classifications. We demonstrate that such alignments are feasible for two classifications of primates corresponding to the second and third MSW editions. Our approach has three main components: (i) use of taxonomic concept labels, that is name sec. author (where sec. means according to), to assemble each concept hierarchy separately via parent/child relationships; (ii) articulation of select concepts across the two hierarchies with user-provided Region Connection Calculus (RCC-5) relationships; and (iii) the use of an Answer Set Programming toolkit to infer and visualize logically consistent alignments of these input constraints. Our use case entails the Primates sec. Groves (1993; MSW2-317 taxonomic concepts; 233 at the species level) and Primates sec. Groves (2005; MSW3-483 taxonomic concepts; 376 at the species level). Using 402 RCC-5 input articulations, the reasoning process yields a single, consistent alignment and 153,111 Maximally Informative Relations that constitute a comprehensive meaning resolution map for every concept pair in the Primates sec. MSW2/MSW3. The complete alignment, and various partitions thereof, facilitate quantitative analyses of name:meaning dissociation, revealing that nearly one in three taxonomic names are not reliable across treatments

Non-human Primate Models for Brain Disorders - Towards Genetic Manipulations via Innovative Technology.

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Qiu, Zilong; Li, Xiao

2017-04-01

Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

Longitudinal characterization of Escherichia coli in healthy captive nonhuman primates

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Jonathan B Clayton

2014-11-01

Full Text Available The gastrointestinal (GI tracts of nonhuman primates are well known to harbor Escherichia coli, a known commensal of humans and animals. While E. coli is a normal inhabitant of the mammalian gut, it also exists in a number of pathogenic forms or pathotypes, including those with predisposition for the GI tract, as well the urogenital tract. Diarrhea in captive nonhuman primates (NHPs has long been a problem in both zoo settings and research colonies, including the Como Zoo. It is an animal welfare concern, as well as a public health concern. E. coli has not been extensively studied in correlation with diarrhea in captive primates; therefore, a study was performed during the summer of 2009 in collaboration with a zoo in Saint Paul, MN, which was experiencing an increased incidence and severity of diarrhea among their NHP collection. Fresh fecal samples were collected weekly from each member of the primate collection, between June and August of 2009, and E. coli were isolated. A total of 33 individuals were included in the study, representing eight species. E. coli isolates were examined for their genetic relatedness, phylogenetic relationships, plasmid replicon types, virulence gene profiles, and antimicrobial susceptibility profiles. A number of isolates were identified containing virulence genes commonly found in several different E. coli pathotypes, and there was evidence of clonal transmission of isolates between animals and over time. Overall, the manifestation of chronic diarrhea in the Como Zoo primate collection is a complex problem whose solution will require regular screening for microbial agents and consideration of environmental causes. This study provides some insight towards the sharing of enteric bacteria between such animals.

Evidence of public engagement with science: visitor learning at a zoo-housed primate research centre.

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Bridget M Waller

Full Text Available Primate behavioural and cognitive research is increasingly conducted on direct public view in zoo settings. The potential of such facilities for public engagement with science is often heralded, but evidence of tangible, positive effects on public understanding is rare. Here, the effect of a new zoo-based primate research centre on visitor behaviour, learning and attitudes was assessed using a quasi-experimental design. Zoo visitors approached the primate research centre more often when a scientist was present and working with the primates, and reported greater awareness of primates (including conservation compared to when the scientist was not present. Visitors also reported greater perceived learning when the scientist was present. Installation of information signage had no main effect on visitor attitudes or learning. Visitors who interacted with the signage, however, demonstrated increased knowledge and understanding when asked about the specific information present on the signs (which was related to the ongoing facial expression research at the research centre. The findings show that primate behaviour research centres on public view can have a demonstrable and beneficial effect on public understanding of science.

Evidence of public engagement with science: visitor learning at a zoo-housed primate research centre.

Science.gov (United States)

Waller, Bridget M; Peirce, Kate; Mitchell, Heidi; Micheletta, Jerome

2012-01-01

Primate behavioural and cognitive research is increasingly conducted on direct public view in zoo settings. The potential of such facilities for public engagement with science is often heralded, but evidence of tangible, positive effects on public understanding is rare. Here, the effect of a new zoo-based primate research centre on visitor behaviour, learning and attitudes was assessed using a quasi-experimental design. Zoo visitors approached the primate research centre more often when a scientist was present and working with the primates, and reported greater awareness of primates (including conservation) compared to when the scientist was not present. Visitors also reported greater perceived learning when the scientist was present. Installation of information signage had no main effect on visitor attitudes or learning. Visitors who interacted with the signage, however, demonstrated increased knowledge and understanding when asked about the specific information present on the signs (which was related to the ongoing facial expression research at the research centre). The findings show that primate behaviour research centres on public view can have a demonstrable and beneficial effect on public understanding of science.

The pervasive role of social learning in primate lifetime development.

Science.gov (United States)

Whiten, Andrew; van de Waal, Erica

2018-01-01

In recent decades, an accelerating research effort has exploited a substantial diversity of methodologies to garner mounting evidence for social learning and culture in many species of primate. As in humans, the evidence suggests that the juvenile phases of non-human primates' lives represent a period of particular intensity in adaptive learning from others, yet the relevant research remains scattered in the literature. Accordingly, we here offer what we believe to be the first substantial collation and review of this body of work and its implications for the lifetime behavioral ecology of primates. We divide our analysis into three main phases: a first phase of learning focused on primary attachment figures, typically the mother; a second phase of selective learning from a widening array of group members, including some with expertise that the primary figures may lack; and a third phase following later dispersal, when a migrant individual encounters new ecological and social circumstances about which the existing residents possess expertise that can be learned from. Collating a diversity of discoveries about this lifetime process leads us to conclude that social learning pervades primate ontogenetic development, importantly shaping locally adaptive knowledge and skills that span multiple aspects of the behavioral repertoire.

Astrocyte Apoptosis and HIV Replication Are Modulated in Host Cells Coinfected with Trypanosoma cruzi

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Javier M. Urquiza

2017-08-01

Full Text Available The protozoan Trypanosoma cruzi is the etiological agent of Chagas disease. In immunosuppressed individuals, as it occurs in the coinfection with human immunodeficiency virus (HIV, the central nervous system may be affected. In this regard, reactivation of Chagas disease is severe and often lethal, and it accounts for meningoencephalitis. Astrocytes play a crucial role in the environment maintenance of healthy neurons; however, they can host HIV and T. cruzi. In this report, human astrocytes were infected in vitro with both genetically modified-pathogens to express alternative fluorophore. As evidenced by fluorescence microscopy and flow cytometry, HIV and T. cruzi coexist in the same astrocyte, likely favoring reciprocal interactions. In this context, lower rates of cell death were observed in both T. cruzi monoinfected-astrocytes and HIV-T. cruzi coinfection in comparison with those infected only with HIV. The level of HIV replication is significantly diminished under T. cruzi coinfection, but without affecting the infectivity of the HIV progeny. This interference with viral replication appears to be related to the T. cruzi multiplication rate or its increased intracellular presence but does not require their intracellular cohabitation or infected cell-to-cell contact. Among several Th1/Th2/Th17 profile-related cytokines, only IL-6 was overexpressed in HIV-T. cruzi coinfection exhibiting its cytoprotective role. This study demonstrates that T. cruzi and HIV are able to coinfect astrocytes thus altering viral replication and apoptosis.

Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin α interactions as a novel HIV-1 therapy

International Nuclear Information System (INIS)

Suzuki, Tatsunori; Yamamoto, Norio; Nonaka, Mizuho; Hashimoto, Yoshie; Matsuda, Go; Takeshima, Shin-nosuke; Matsuyama, Megumi; Igarashi, Tatsuhiko; Miura, Tomoyuki; Tanaka, Rie; Kato, Shingo; Aida, Yoko

2009-01-01

The development of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus (HIV) therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. One such target is the interaction between Vpr, one of the accessory gene products of HIV-1 and Importin α, which is crucial, not only for the nuclear import of Vpr, but also for HIV-1 replication in macrophages. We have identified a potential parent compound, hematoxylin, which suppresses Vpr-Importin α interaction, thereby inhibiting HIV-1 replication in a Vpr-dependent manner. Analysis by real-time PCR demonstrated that hematoxylin specifically inhibited nuclear import step of pre-integration complex. Thus, hematoxylin is a new anti-HIV-1 inhibitor that targets the nuclear import of HIV-1 via the Vpr-Importin α interaction, suggesting that a specific inhibitor of the interaction between viral protein and the cellular factor may provide a new strategy for HIV-1 therapy.

Understanding the control of ingestive behavior in primates.

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Wilson, Mark E; Moore, Carla J; Ethun, Kelly F; Johnson, Zachary P

2014-06-01

This article is part of a Special Issue "Energy Balance". Ingestive behavior in free-ranging populations of nonhuman primates is influenced by resource availability and social group organization and provides valuable insight on the evolution of ecologically adaptive behaviors and physiological systems. As captive populations were established, questions regarding proximate mechanisms that regulate food intake in these animals could be more easily addressed. The availability of these captive populations has led to the use of selected species to understand appetite control or metabolic physiology in humans. Recognizing the difficulty of quantitating food intake in free-ranging groups, the use of captive, singly-housed animals provided a distinct advantage though, at the same time, produced a different social ecology from the animals' natural habitat. However, the recent application of novel technologies to quantitate caloric intake and energy expenditure in free-feeding, socially housed monkeys permits prospective studies that can accurately define how food intake changes in response to any number of interventions in the context of a social environment. This review provides an overview of studies examining food intake using captive nonhuman primates organized into three areas: a) neurochemical regulation of food intake in nonhuman primates; b) whether exposure to specific diets during key developmental periods programs differences in diet preferences or changes the expression of feeding related neuropeptides; and c) how psychosocial factors influence appetite regulation. Because feeding patterns are driven by more than just satiety and orexigenic signals, appreciating how the social context influences pattern of feeding in nonhuman primates may be quite informative for understanding the biological complexity of feeding in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Basics of primary immunodeficiencies

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Claudia Hernández-Martínez

2016-05-01

Full Text Available Primary immunodeficiencies (PID are a heterogeneous group of inherited disorders, the etiology are the defects in the development or function of the immune system. The principal PID manifestations are the infections in early age, malignancy and diseases of immune dysregulation as autoimmunity and allergy. PIDs are genetics disorders and most of them are inherited as autosomal recessive, also this group of diseases is more prevalent in males and in childhood. The antibody immunodeficiency is the PID more common in adults. The more frequent disorders are the infections in the respiratory tract, abscesses, candidiasis, diarrhea, BCGosis etc. Initial approach included a complete blood count and quantification of immunoglobulins. The delay in diagnosis could be explained due to a perception that the recurrent infections are normal process or think that they are exclusively of childhood. The early diagnosis of PID by primary care physicians is important to opportune treatment and better prognosis.

Nonhuman primate dermatology: a literature review

Science.gov (United States)

Bernstein, Joseph A.; Didier, Peter J.

2015-01-01

In general, veterinary dermatologists do not have extensive clinical experience of nonhuman primate (NHP) dermatoses. The bulk of the published literature does not provide an organized evidence-based approach to the NHP dermatologic case. The veterinary dermatologist is left to extract information from both human and veterinary dermatology, an approach that can be problematic as it forces the clinician to make diagnostic and therapeutic decisions based on two very disparate bodies of literature. A more cohesive approach to NHP dermatology – without relying on assumptions that NHP pathology most commonly behaves similarly to other veterinary and human disease – is required. This review of the dermatology of NHP species includes discussions of primary dermatoses, as well as diseases where dermatologic signs represent a significant secondary component, provides a first step towards encouraging the veterinary community to study and report the dermatologic diseases of nonhuman primates. PMID:19490576

Effect of land use dynamics on habitat of two sympatric primates in ...

African Journals Online (AJOL)

Competition between growing human population and burgeoning number of primates were investigated at the Boabeng-Fiema monkey sanctuary (BFMS) in Ghana, to determine the effect of habitat change on primates. Remote sensing data, primarily Landsat imagery, were used to analyse the land use cover changes that ...

[Ear, nose, and throat manifestations in patients with primary immunodeficiencies].

Science.gov (United States)

Galicia, G; Betancourt, M A; Canales, L E; Cristerna, L

1999-01-01

To determine the flowgram for the timely diagnosis of the immunodeficiencies congenital primary, based on the demonstrations otorrinolaringol recurrent chronicles to difficult control, with or without associated systemic diseases. Retrospective study, descriptive and observational that included patient with diagnostic of primary known immunodeficiency. They were checked the clinical files to know their evolution and medical treatment-surgical. They were found 10 patient with diagnostic of some primary immunodeficiency; this was made based on the infectious symptoms otolaryngal chronic recurrent to difficult control; they were six men and four women between the four and 36 years old. They were found the following immunodeficiencies: one of hyper-IgM, three by IgG, variable common three, a deficit with C3 of the complement, two of IgA more atopia. The chronicle sinusitis or recurrent and the otitis mean chronicle or recurrent can be the only demonstrations of a patient with primary immunodeficiency. The immunology evaluation must include, at least: hematic biometric completes with differential, seric levels of immunoglobulins, the same as subclass of IgG, C4 and C3 of the complement, response to immunization with proteins (diphtheria and tetanus), and polysaccharide antigens (pneumovax).

CTA1-DD adjuvant promotes strong immunity against human immunodeficiency virus type 1 envelope glycoproteins following mucosal immunization.

Science.gov (United States)

Sundling, Christopher; Schön, Karin; Mörner, Andreas; Forsell, Mattias N E; Wyatt, Richard T; Thorstensson, Rigmor; Karlsson Hedestam, Gunilla B; Lycke, Nils Y

2008-12-01

Strategies to induce potent and broad antibody responses against the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) at both systemic and mucosal sites represent a central goal for HIV-1 vaccine development. Here, we show that the non-toxic CTA1-DD adjuvant promoted mucosal and systemic humoral and cell-mediated immune responses following intranasal (i.n.) immunizations with trimeric or monomeric forms of HIV-1 Env in mice and in non-human primates. Env-specific IgG subclasses in the serum of immunized mice reflected a balanced Th1/Th2 type of response. Strikingly, i.n. immunizations with Env and the CTA1-DD adjuvant induced substantial levels of mucosal anti-Env IgA in bronchial alveolar lavage and also detectable levels in vaginal secretions. By contrast, parenteral immunizations of Env formulated in Ribi did not stimulate mucosal IgA responses, while the two adjuvants induced a similar distribution of Env-specific IgG-subclasses in serum. A single parenteral boost with Env in Ribi adjuvant into mice previously primed i.n. with Env and CTA1-DD, augmented the serum anti-Env IgG levels to similar magnitudes as those observed after three intraperitoneal immunizations with Env in Ribi. The augmenting potency of CTA1-DD was similar to that of LTK63 or CpG oligodeoxynucleotides (ODN). However, in contrast to CpG ODN, the effect of CTA1-DD and LTK63 appeared to be independent of MyD88 and toll-like receptor signalling. This is the first demonstration that CTA1-DD augments specific immune responses also in non-human primates, suggesting that this adjuvant could be explored further as a clinically safe mucosal vaccine adjuvant for humoral and cell-mediated immunity against HIV-1 Env.

Transplantation of autologous synovial mesenchymal stem cells promotes meniscus regeneration in aged primates.

Science.gov (United States)

Kondo, Shimpei; Muneta, Takeshi; Nakagawa, Yusuke; Koga, Hideyuki; Watanabe, Toshifumi; Tsuji, Kunikazu; Sotome, Shinichi; Okawa, Atsushi; Kiuchi, Shinji; Ono, Hideo; Mizuno, Mitsuru; Sekiya, Ichiro

2017-06-01

Transplantation of aggregates of synovial mesenchymal stem cells (MSCs) enhanced meniscus regeneration in rats. Anatomy and biological properties of the meniscus depend on animal species. To apply this technique clinically, it is valuable to investigate the use of animals genetically close to humans. We investigated whether transplantation of aggregates of autologous synovial MSCs promoted meniscal regeneration in aged primates. Chynomolgus primates between 12 and 13 years old were used. After the anterior halves of the medial menisci in both knees were removed, an average of 14 aggregates consisting of 250,000 synovial MSCs were transplanted onto the meniscus defect. No aggregates were transplanted to the opposite knee for the control. Meniscus and articular cartilage were analyzed macroscopically, histologically, and by MRI T1rho mapping at 8 (n = 3) and 16 weeks (n = 4). The medial meniscus was larger and the modified Pauli's histological score for the regenerated meniscus was better in the MSC group than in the control group in each primate at 8 and 16 weeks. Mankin's score for the medial femoral condyle cartilage was better in the MSC group than in the control group in all primates at 16 weeks. T1rho value for both the regenerated meniscus and adjacent articular cartilage in the MSC group was closer to the normal meniscus than in the control group in all primates at 16 weeks. Transplantation of aggregates of autologous synovial MSCs promoted meniscus regeneration and delayed progression of degeneration of articular cartilage in aged primates. This is the first report dealing with meniscus regeneration in primates. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1274-1282, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

A new primate assemblage from La Verrerie de Roches (Middle Eocene, Switzerland).

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Minwer-Barakat, Raef; Marigó, Judit; Becker, Damien; Costeur, Loïc

2017-12-01

Primates reached a great abundance and diversity during the Eocene, favored by warm temperatures and by the development of dense forests throughout the Northern Hemisphere. Here we describe new primate material from La Verrerie de Roches, a Middle Eocene karstic infill situated in the Jura Region (Switzerland), consisting of more than 80 dental remains. The primate assemblage from La Verrerie de Roches includes five different taxa. The best represented primate is Necrolemur aff. anadoni, similar in size and overall morphology to Necrolemur anadoni but resembling in some features the younger species Necrolemur antiquus. Microchoerines are also represented by two species of Pseudoloris, P. pyrenaicus and Pseudoloris parvulus, constituting the unique joint record of these two species known up to now. Remains of Adapiformes are limited to one isolated tooth of a large anchomomyin and another tooth belonging to the small adapine Microadapis cf. sciureus. The studied primate association allows assigning La Verrerie de Roches to the Robiacian Land Mammal Age. More specifically, this site can be confidently situated between the MP15 and MP16 reference levels, although the primate assemblage probably indicates some degree of temporal mixing. This is the first record of P. pyrenaicus and a form closely related to N. anadoni out of the Iberian Peninsula. The identification of these microchoerines in Switzerland gives further support to the connection of NE Spain and Central Europe during the Middle Eocene. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection.

Science.gov (United States)

Subramanian, T; Zhao, Ling-Jun; Chinnadurai, G

2013-09-01

Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP-E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP-E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Immunodeficiencies and autoimmune diseases: common variable immunodeficiency and Crohn-like

OpenAIRE

Saldaña-Dueñas, Cristina; Rubio-Iturria, Saioa

2016-01-01

Background: Common variable immunodeficiency (CVI) gives a major risk of principally respiratory and digestive infections. It is associated with autoimmune diseases, granulomatous process and neoplasias. The digestive clinic is common, in 10% of patients it is the only symptom, and 60% present chronic diarrhea. Clinically it can be confused and related with other pathologies such as inflammatory bowel disease which is infrequent (2-13%). Case report: We present the case of a patient with CVI ...

Vitamin D inhibits human immunodeficiency virus type 1 and Mycobacterium tuberculosis infection in macrophages through the induction of autophagy.

Directory of Open Access Journals (Sweden)

Grant R Campbell

Full Text Available Low vitamin D levels in human immunodeficiency virus type-1 (HIV infected persons are associated with more rapid disease progression and increased risk for Mycobacterium tuberculosis infection. We have previously shown that 1α,25-dihydroxycholecalciferol (1,25D3, the active form of vitamin D, inhibits HIV replication in human macrophages through the induction of autophagy. In this study, we report that physiological concentrations of 1,25D3 induce the production of the human cathelicidin microbial peptide (CAMP and autophagic flux in HIV and M. tuberculosis co-infected human macrophages which inhibits mycobacterial growth and the replication of HIV. Using RNA interference for Beclin-1 and the autophagy-related 5 homologue, combined with the chemical inhibitors of autophagic flux, bafilomycin A₁, an inhibitor of autophagosome-lysosome fusion and subsequent acidification, and SID 26681509 an inhibitor of the lysosome hydrolase cathepsin L, we show that the 1,25D3-mediated inhibition of HIV replication and mycobacterial growth during single infection or dual infection is dependent not only upon the induction of autophagy, but also through phagosomal maturation. Moreover, through the use of RNA interference for CAMP, we demonstrate that cathelicidin is essential for the 1,25D3 induced autophagic flux and inhibition of HIV replication and mycobacterial growth. The present findings provide a biological explanation for the benefits and importance of vitamin D sufficiency in HIV and M. tuberculosis-infected persons, and provide new insights into novel approaches to prevent and treat HIV infection and related opportunistic infections.

Inhibitors of Deubiquitinating Enzymes Block HIV-1 Replication and Augment the Presentation of Gag-Derived MHC-I Epitopes.

Science.gov (United States)

Setz, Christian; Friedrich, Melanie; Rauch, Pia; Fraedrich, Kirsten; Matthaei, Alina; Traxdorf, Maximilian; Schubert, Ulrich

2017-08-12

In recent years it has been well established that two major constituent parts of the ubiquitin proteasome system (UPS)-the proteasome holoenzymes and a number of ubiquitin ligases-play a crucial role, not only in virus replication but also in the regulation of the immunogenicity of human immunodeficiency virus type 1 (HIV-1). However, the role in HIV-1 replication of the third major component, the deubiquitinating enzymes (DUBs), has remained largely unknown. In this study, we show that the DUB-inhibitors (DIs) P22077 and PR-619, specific for the DUBs USP7 and USP47, impair Gag processing and thereby reduce the infectivity of released virions without affecting viral protease activity. Furthermore, the replication capacity of X4- and R5-tropic HIV-1 NL4-3 in human lymphatic tissue is decreased upon treatment with these inhibitors without affecting cell viability. Most strikingly, combinatory treatment with DIs and proteasome inhibitors synergistically blocks virus replication at concentrations where mono-treatment was ineffective, indicating that DIs can boost the therapeutic effect of proteasome inhibitors. In addition, P22077 and PR-619 increase the polyubiquitination of Gag and thus its entry into the UPS and the major histocompatibility complex (MHC)-I pathway. In summary, our data point towards a model in which specific inhibitors of DUBs not only interfere with virus spread but also increase the immune recognition of HIV-1 expressing cells.

Detection of Weakly Conserved Ancestral Mammalian RegulatorySequences by Primate Comparisons

Energy Technology Data Exchange (ETDEWEB)

Wang, Qian-fei; Prabhakar, Shyam; Chanan, Sumita; Cheng,Jan-Fang; Rubin, Edward M.; Boffelli, Dario

2006-06-01

Genomic comparisons between human and distant, non-primatemammals are commonly used to identify cis-regulatory elements based onconstrained sequence evolution. However, these methods fail to detectcryptic functional elements, which are too weakly conserved among mammalsto distinguish from nonfunctional DNA. To address this problem, weexplored the potential of deep intra-primate sequence comparisons. Wesequenced the orthologs of 558 kb of human genomic sequence, coveringmultiple loci involved in cholesterol homeostasis, in 6 nonhumanprimates. Our analysis identified 6 noncoding DNA elements displayingsignificant conservation among primates, but undetectable in more distantcomparisons. In vitro and in vivo tests revealed that at least three ofthese 6 elements have regulatory function. Notably, the mouse orthologsof these three functional human sequences had regulatory activity despitetheir lack of significant sequence conservation, indicating that they arecryptic ancestral cis-regulatory elements. These regulatory elementscould still be detected in a smaller set of three primate speciesincluding human, rhesus and marmoset. Since the human and rhesus genomesequences are already available, and the marmoset genome is activelybeing sequenced, the primate-specific conservation analysis describedhere can be applied in the near future on a whole-genome scale, tocomplement the annotation provided by more distant speciescomparisons.

Towards Transgenic Primates: What can we learn from mouse genetics?

Institute of Scientific and Technical Information of China (English)

KUANG Hui; WANG Phillip L.; TSIEN Joe Z.

2009-01-01

Considering the great physiological and behavioral similarities with humans, monkeys represent the ideal models not only for the study of complex cognitive behavior but also for the precUnical research and development of novel therapeutics for treating human diseases. Various powerful genetic tech-nologies initially developed for making mouse models are being explored for generating transgenic primate models. We review the latest genetic engineering technologies and discuss the potentials and limitations for systematic production of transgenic primates.

Towards Transgenic Primates:What can we learn from mouse genetics?

Institute of Scientific and Technical Information of China (English)

WANG; Phillip; L.; TSIEN; Joe; Z.

2009-01-01

Considering the great physiological and behavioral similarities with humans,monkeys represent the ideal models not only for the study of complex cognitive behavior but also for the preclinical research and development of novel therapeutics for treating human diseases.Various powerful genetic tech-nologies initially developed for making mouse models are being explored for generating transgenic primate models.We review the latest genetic engineering technologies and discuss the potentials and limitations for systematic production of transgenic primates.

Precursors to language: Social cognition and pragmatic inference in primates.

Science.gov (United States)

Seyfarth, Robert M; Cheney, Dorothy L

2017-02-01

Despite their differences, human language and the vocal communication of nonhuman primates share many features. Both constitute forms of coordinated activity, rely on many shared neural mechanisms, and involve discrete, combinatorial cognition that includes rich pragmatic inference. These common features suggest that during evolution the ancestors of all modern primates faced similar social problems and responded with similar systems of communication and cognition. When language later evolved from this common foundation, many of its distinctive features were already present.

Transformation and Tumorigenicity Testing of Simian Cell Lines and Evaluation of Poliovirus Replication.

Directory of Open Access Journals (Sweden)

Silvia Dotti

Full Text Available The key role of cell cultures in different scientific fields is worldwide recognized, both as in vitro research models alternative to laboratory animals and substrates for biological production. However, many safety concerns rise from the use of animal/human cell lines that may be tumorigenic, leading to potential adverse contaminations in cell-derived biologicals. In order to evaluate the suitability of 13 different cell lines for Poliovirus vaccine production, safety and quality, in vitro/in vivo tumorigenicity and Poliovirus propagation properties were evaluated. Our results revealed that non-human primate cell lines CYNOM-K1, FRhK-4, 4MBr-5 and 4647 are free of tumorigenic features and represent highly susceptible substrates for attenuated Sabin Poliovirus strains. In particular, FRhK-4 and 4647 cell lines are characterized by a higher in vitro replication, resulting indicated for the use in large-scale production field.

Cocaine is pharmacologically active in the nonhuman primate fetal brain

DEFF Research Database (Denmark)

Benveniste, Helene; Fowler, Joanna S; Rooney, William D

2010-01-01

Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third-trimester ......Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third......-trimester pregnant nonhuman primates, cocaine at doses typically used by drug abusers significantly increased brain glucose metabolism to the same extent in the mother as in the fetus (approximately 100%). Inasmuch as brain glucose metabolism is a sensitive marker of brain function, the current findings provide...

Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication.

Science.gov (United States)

Thenin-Houssier, Suzie; de Vera, Ian Mitchelle S; Pedro-Rosa, Laura; Brady, Angela; Richard, Audrey; Konnick, Briana; Opp, Silvana; Buffone, Cindy; Fuhrmann, Jakob; Kota, Smitha; Billack, Blase; Pietka-Ottlik, Magdalena; Tellinghuisen, Timothy; Choe, Hyeryun; Spicer, Timothy; Scampavia, Louis; Diaz-Griffero, Felipe; Kojetin, Douglas J; Valente, Susana T

2016-04-01

The human immunodeficiency virus type 1 (HIV-1) capsid plays crucial roles in HIV-1 replication and thus represents an excellent drug target. We developed a high-throughput screening method based on a time-resolved fluorescence resonance energy transfer (HTS-TR-FRET) assay, using the C-terminal domain (CTD) of HIV-1 capsid to identify inhibitors of capsid dimerization. This assay was used to screen a library of pharmacologically active compounds, composed of 1,280in vivo-active drugs, and identified ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], an organoselenium compound, as an inhibitor of HIV-1 capsid CTD dimerization. Nuclear magnetic resonance (NMR) spectroscopic analysis confirmed the direct interaction of ebselen with the HIV-1 capsid CTD and dimer dissociation when ebselen is in 2-fold molar excess. Electrospray ionization mass spectrometry revealed that ebselen covalently binds the HIV-1 capsid CTD, likely via a selenylsulfide linkage with Cys198 and Cys218. This compound presents anti-HIV activity in single and multiple rounds of infection in permissive cell lines as well as in primary peripheral blood mononuclear cells. Ebselen inhibits early viral postentry events of the HIV-1 life cycle by impairing the incoming capsid uncoating process. This compound also blocks infection of other retroviruses, such as Moloney murine leukemia virus and simian immunodeficiency virus, but displays no inhibitory activity against hepatitis C and influenza viruses. This study reports the use of TR-FRET screening to successfully identify a novel capsid inhibitor, ebselen, validating HIV-1 capsid as a promising target for drug development. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Changes in B cell immunophenotype in common variable immunodeficiency: cause or effect – is bronchiectasis indicative of undiagnosed immunodeficiency?

Science.gov (United States)

Bright, P; Grigoriadou, S; Kamperidis, P; Buckland, M; Hickey, A; Longhurst, H J

2013-01-01

Common variable immunodeficiency (CVID) is the most common severe primary immunodeficiency, but the pathology of this condition is poorly understood. CVID involves a defect in the production of immunoglobulin from B cells, with a subsequent predisposition to infections. Approximately 10–20% of cases are inherited, but even in families with a genetic defect the penetrance is far from complete. A classification system for CVID has been suggested (EUROclass) based on B cell immunophenotyping, but it has not been shown that altered B cell immunophenotype is not a consequence of the complications and treatment of CVID. This study compares the EUROclass B cell immunophenotype of CVID patients (n = 30) with suitable disease controls with bronchiectasis (n = 11), granulomatous disease (Crohn's disease) (n = 9) and neurological patients on immunoglobulin treatment (n = 6). The results of this study correlate with previous literature, that alterations in B cell immunophenotype are associated strongly with CVID. Interestingly, three of the 11 bronchiectasis patients without known immunodeficiency had an altered B cell immunophenotype, suggesting the possibility of undiagnosed immunodeficiency, or that bronchiectasis may cause a secondary alteration in B cell immunophenotype. This study showed a significant difference in B cell immunophenotype between CVID patients compared to disease control groups of granulomatous disease and immunoglobulin treatment. This suggests that granulomatous disease (in Crohn's disease) and immunoglobulin treatment (for chronic neurological conditions) are not causal of an altered B cell immunophenotype in these control populations. PMID:23286946

Differential Impact of In Vivo CD8+ T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques.

Science.gov (United States)

Chowdhury, Ankita; Hayes, Timothy L; Bosinger, Steven E; Lawson, Benton O; Vanderford, Thomas; Schmitz, Joern E; Paiardini, Mirko; Betts, Michael; Chahroudi, Ann; Estes, Jacob D; Silvestri, Guido

2015-09-01

Numerous studies have demonstrated that CD8(+) T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8(+) T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.v.) with SIVmac239. At day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) were CD8 depleted by i.v. administration of the antibody M-T807R1. As expected, CD8 depletion resulted in increased virus replication, more prominently in controllers than progressors, which correlated inversely with predepletion viremia. Of note, the feature of CD8(+) T lymphocyte predepletion that correlated best with the increase in viremia postdepletion was the level of CD8(+) T-bet(+) lymphocytes. We next found that CD8 depletion resulted in a homogenous increase of SIV RNA in superficial and mesenteric lymph nodes, spleen, and the gastrointestinal tract of both controllers and progressors. Interestingly, the level of SIV DNA increased postdepletion in both CD4(+) central memory T lymphocytes (TCM) and CD4(+) effector memory T lymphocytes (TEM) in progressor RMs but decreased in the CD4(+) TCM of 4 out of 5 controllers. Finally, we found that CD8 depletion is associated with a greater increase in CD4(+) T lymphocyte activation (measured by Ki-67 expression) in controllers than in progressors. Overall, these data reveal a differential impact of CD8(+) T lymphocyte depletion between controller and progressor SIV-infected RMs, emphasizing the complexity of the in vivo antiviral role of CD8(+) T lymphocytes. In this study, we further dissect the impact of CD8(+) T lymphocytes on HIV/SIV replication during SIV infection. CD8(+) T lymphocyte depletion leads to a relatively homogenous increase in viral replication in peripheral blood and tissues. CD8(+) T lymphocyte depletion

From tetrapods to primates: conserved developmental mechanisms in diverging ecological adaptations.

Science.gov (United States)

Aboitiz, Francisco; Montiel, Juan F

2012-01-01

Primates are endowed with a brain about twice the size that of a mammal with the same body size, and humans have the largest brain relative to body size of all animals. This increase in brain size may be related to the acquisition of higher cognitive skills that permitted more complex social interactions, the evolution of culture, and the eventual ability to manipulate the environment. Nevertheless, in its internal structure, the primate brain shares a very conserved design with other mammals, being covered by a six-layered neocortex that, although expands disproportionately to other brain components, it does so following relatively well-defined allometric trends. Thus, the most fundamental events generating the basic design of the primate and human brain took place before the appearance of the first primate-like animal. Presumably, the earliest mammals already displayed a brain morphology radically different from that of their ancestors and that of their sister group, the reptiles, being characterized by the presence of an incipient neocortex that underwent an explosive growth in subsequent mammal evolution. In this chapter, we propose an integrative hypothesis for the origin of the mammalian neocortex, by considering the developmental modifications, functional networks, and ecological adaptations involved in the generation of this structure during the cretaceous period. Subsequently, the expansion of the primate brain is proposed to have relied on the amplification of the same, or very similar, developmental mechanisms as those involved in its primary origins, even in different ecological settings. Copyright © 2012 Elsevier B.V. All rights reserved.

Lentiviral Gag assembly analyzed through the functional characterization of chimeric simian immunodeficiency viruses expressing different domains of the feline immunodeficiency virus capsid protein.

Directory of Open Access Journals (Sweden)

María J Esteva

Full Text Available To gain insight into the functional relationship between the capsid (CA domains of the Gag polyproteins of simian and feline immunodeficiency viruses (SIV and FIV, respectively, we constructed chimeric SIVs in which the CA-coding region was partially or totally replaced by the equivalent region of the FIV CA. The phenotypic characterization of the chimeras allowed us to group them into three categories: the chimeric viruses that, while being assembly-competent, exhibit a virion-associated unstable FIV CA; a second group represented only by the chimeric SIV carrying the N-terminal domain (NTD of the FIV CA which proved to be assembly-defective; and a third group constituted by the chimeric viruses that produce virions exhibiting a mature and stable FIV CA protein, and which incorporate the envelope glycoprotein and contain wild-type levels of viral genome RNA and reverse transcriptase. Further analysis of the latter group of chimeric SIVs demonstrated that they are non-infectious due to a post-entry impairment, such as uncoating of the viral core, reverse transcription or nuclear import of the preintegration complex. Furthermore, we show here that the carboxyl-terminus domain (CTD of the FIV CA has an intrinsic ability to dimerize in vitro and form high-molecular-weight oligomers, which, together with our finding that the FIV CA-CTD is sufficient to confer assembly competence to the resulting chimeric SIV Gag polyprotein, provides evidence that the CA-CTD exhibits more functional plasticity than the CA-NTD. Taken together, our results provide relevant information on the biological relationship between the CA proteins of primate and nonprimate lentiviruses.

Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates.

Directory of Open Access Journals (Sweden)

Wilmon F Grant

2011-02-01

Full Text Available To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD contained equivalent levels of n-3 fatty acids (FA's and higher levels of n-6 FA's than the control diet (CTR, we found significant decreases in docosahexaenoic acid (DHA and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6:n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6:n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.

Prevalence of gastrointestinal parasites in captive non-human primates of twenty-four zoological gardens in China.

Science.gov (United States)

Li, Mei; Zhao, Bo; Li, Bo; Wang, Qiang; Niu, Lili; Deng, Jiabo; Gu, Xiaobin; Peng, Xuerong; Wang, Tao; Yang, Guangyou

2015-06-01

Captive primates are susceptible to gastrointestinal (GIT) parasitic infections, which are often zoonotic and can contribute to morbidity and mortality. Fecal samples were examined by the means of direct smear, fecal flotation, fecal sedimentation, and fecal cultures. Of 26.51% (317/1196) of the captive primates were diagnosed gastrointestinal parasitic infections. Trichuris spp. were the most predominant in the primates, while Entamoeba spp. were the most prevalent in Old World monkeys (P primates and the safety of animal keepers and visitors. © 2015 The Authors. Journal of Medical Primatology Published by John Wiley & Sons Ltd.

Primate auditory recognition memory performance varies with sound type.

Science.gov (United States)

Ng, Chi-Wing; Plakke, Bethany; Poremba, Amy

2009-10-01

Neural correlates of auditory processing, including for species-specific vocalizations that convey biological and ethological significance (e.g., social status, kinship, environment), have been identified in a wide variety of areas including the temporal and frontal cortices. However, few studies elucidate how non-human primates interact with these vocalization signals when they are challenged by tasks requiring auditory discrimination, recognition and/or memory. The present study employs a delayed matching-to-sample task with auditory stimuli to examine auditory memory performance of rhesus macaques (Macaca mulatta), wherein two sounds are determined to be the same or different. Rhesus macaques seem to have relatively poor short-term memory with auditory stimuli, and we examine if particular sound types are more favorable for memory performance. Experiment 1 suggests memory performance with vocalization sound types (particularly monkey), are significantly better than when using non-vocalization sound types, and male monkeys outperform female monkeys overall. Experiment 2, controlling for number of sound exemplars and presentation pairings across types, replicates Experiment 1, demonstrating better performance or decreased response latencies, depending on trial type, to species-specific monkey vocalizations. The findings cannot be explained by acoustic differences between monkey vocalizations and the other sound types, suggesting the biological, and/or ethological meaning of these sounds are more effective for auditory memory. 2009 Elsevier B.V.

Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen presenting cells and induces efficient CD4+ T helper responses.

Science.gov (United States)

Fiorentini, Simona; Marconi, Peggy; Avolio, Manuela; Marini, Elena; Garrafa, Emirena; Caracciolo, Sonia; Rossi, Daniele; Bozac, Alexandra; Becker, Pablo D; Gentili, Francesca; Facchetti, Fabio; Guzman, Carlos A; Manservigi, Roberto; Caruso, Arnaldo

2007-07-01

Both neutralizing antibodies and cytotoxic T-cells are necessary to control a viral infection. However, vigorous T helper responses are essential for their elicitation and maintenance. Here we show that a recombinant replication-deficient Herpes Simplex Virus (HSV)-1 vector encoding the Human Immunodeficiency Virus (HIV)-1 matrix protein p17 (T0-p17) was capable of infecting professional antigen presenting cells (APCs) in vitro and in vivo. The injection of T0-p17 in the mouse dermis generated a strong p17-specific CD4+ T helper response preceding both p17-specific humoral and effector T cell responses. Moreover, we show that T0-p17 infection did not interfere with the endogenous processing of the transgene encoded antigen, since infected APCs were able to evoke a strong recall response in vitro. Our results demonstrate that replication-deficient HSV vectors can be appealing candidates for the development of vaccines able to trigger T helper responses.

Deep hierarchies in the primate visual cortex: what can we learn for computer vision?

Science.gov (United States)

Krüger, Norbert; Janssen, Peter; Kalkan, Sinan; Lappe, Markus; Leonardis, Ales; Piater, Justus; Rodríguez-Sánchez, Antonio J; Wiskott, Laurenz

2013-08-01

Computational modeling of the primate visual system yields insights of potential relevance to some of the challenges that computer vision is facing, such as object recognition and categorization, motion detection and activity recognition, or vision-based navigation and manipulation. This paper reviews some functional principles and structures that are generally thought to underlie the primate visual cortex, and attempts to extract biological principles that could further advance computer vision research. Organized for a computer vision audience, we present functional principles of the processing hierarchies present in the primate visual system considering recent discoveries in neurophysiology. The hierarchical processing in the primate visual system is characterized by a sequence of different levels of processing (on the order of 10) that constitute a deep hierarchy in contrast to the flat vision architectures predominantly used in today's mainstream computer vision. We hope that the functional description of the deep hierarchies realized in the primate visual system provides valuable insights for the design of computer vision algorithms, fostering increasingly productive interaction between biological and computer vision research.

Social learning, culture and the 'socio-cultural brain' of human and non-human primates.

Science.gov (United States)

Whiten, Andrew; van de Waal, Erica

2017-11-01

Noting important recent discoveries, we review primate social learning, traditions and culture, together with associated findings about primate brains. We survey our current knowledge of primate cultures in the wild, and complementary experimental diffusion studies testing species' capacity to sustain traditions. We relate this work to theories that seek to explain the enlarged brain size of primates as specializations for social intelligence, that have most recently extended to learning from others and the cultural transmission this permits. We discuss alternative theories and review a variety of recent findings that support cultural intelligence hypotheses for primate encephalization. At a more fine-grained neuroscientific level we focus on the underlying processes of social learning, especially emulation and imitation. Here, our own and others' recent research has established capacities for bodily imitation in both monkeys and apes, results that are consistent with a role for the mirror neuron system in social learning. We review important convergences between behavioural findings and recent non-invasive neuroscientific studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative primate obstetrics: Observations of 15 diurnal births in wild gelada monkeys (Theropithecus gelada) and their implications for understanding human and nonhuman primate birth evolution.

Science.gov (United States)

Nguyen, Nga; Lee, Laura M; Fashing, Peter J; Nurmi, Niina O; Stewart, Kathrine M; Turner, Taylor J; Barry, Tyler S; Callingham, Kadie R; Goodale, C Barret; Kellogg, Bryce S; Burke, Ryan J; Bechtold, Emily K; Claase, Megan J; Eriksen, G Anita; Jones, Sorrel C Z; Kerby, Jeffrey T; Kraus, Jacob B; Miller, Carrie M; Trew, Thomas H; Zhao, Yi; Beierschmitt, Evan C; Ramsay, Malcolm S; Reynolds, Jason D; Venkataraman, Vivek V

2017-05-01

The birth process has been studied extensively in many human societies, yet little is known about this essential life history event in other primates. Here, we provide the most detailed account of behaviors surrounding birth for any wild nonhuman primate to date. Over a recent ∼10-year period, we directly observed 15 diurnal births (13 live births and 2 stillbirths) among geladas (Theropithecus gelada) at Guassa, Ethiopia. During each birth, we recorded the occurrence (or absence) of 16 periparturitional events, chosen for their potential to provide comparative evolutionary insights into the factors that shaped birth behaviors in humans and other primates. We found that several events (e.g., adopting standing crouched positions, delivering infants headfirst) occurred during all births, while other events (e.g., aiding the infant from the birth canal, licking infants following delivery, placentophagy) occurred during, or immediately after, most births. Moreover, multiparas (n = 9) were more likely than primiparas (n = 6) to (a) give birth later in the day, (b) isolate themselves from nearby conspecifics while giving birth, (c) aid the infant from the birth canal, and (d) consume the placenta. Our results suggest that prior maternal experience may contribute to greater competence or efficiency during the birth process. Moreover, face presentations (in which infants are born with their neck extended and their face appearing first, facing the mother) appear to be the norm for geladas. Lastly, malpresentations (in which infants are born in the occiput anterior position more typical of human infants) may be associated with increased mortality in this species. We compare the birth process in geladas to those in other primates (including humans) and discuss several key implications of our study for advancing understanding of obstetrics and the mechanism of labor in humans and nonhuman primates. © 2017 Wiley Periodicals, Inc.

Inhibitory function of adapter-related protein complex 2 alpha 1 subunit in the process of nuclear translocation of human immunodeficiency virus type 1 genome

International Nuclear Information System (INIS)

Kitagawa, Yukiko; Kameoka, Masanori; Shoji-Kawata, Sanae; Iwabu, Yukie; Mizuta, Hiroyuki; Tokunaga, Kenzo; Fujino, Masato; Natori, Yukikazu; Yura, Yoshiaki; Ikuta, Kazuyoshi

2008-01-01

The transfection of human cells with siRNA against adapter-related protein complex 2 alpha 1 subunit (AP2α) was revealed to significantly up-regulate the replication of human immunodeficiency virus type 1 (HIV-1). This effect was confirmed by cell infection with vesicular stomatitis virus G protein-pseudotyped HIV-1 as well as CXCR4-tropic and CCR5-tropic HIV-1. Viral adsorption, viral entry and reverse transcription processes were not affected by cell transfection with siRNA against AP2α. In contrast, viral nuclear translocation as well as the integration process was significantly up-regulated in cells transfected with siRNA against AP2α. Confocal fluorescence microscopy revealed that a subpopulation of AP2α was not only localized in the cytoplasm but was also partly co-localized with lamin B, importin β and Nup153, implying that AP2α negatively regulates HIV-1 replication in the process of nuclear translocation of viral DNA in the cytoplasm or the perinuclear region. We propose that AP2α may be a novel target for disrupting HIV-1 replication in the early stage of the viral life cycle

Molecular Evolution of the Glycosyltransferase 6 Gene Family in Primates

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Eliane Evanovich

2016-01-01

Full Text Available Glycosyltransferase 6 gene family includes ABO, Ggta1, iGb3S, and GBGT1 genes and by three putative genes restricted to mammals, GT6m6, GTm6, and GT6m7, only the latter is found in primates. GT6 genes may encode functional and nonfunctional proteins. Ggta1 and GBGT1 genes, for instance, are pseudogenes in catarrhine primates, while iGb3S gene is only inactive in human, bonobo, and chimpanzee. Even inactivated, these genes tend to be conversed in primates. As some of the GT6 genes are related to the susceptibility or resistance to parasites, we investigated (i the selective pressure on the GT6 paralogs genes in primates; (ii the basis of the conservation of iGb3S in human, chimpanzee, and bonobo; and (iii the functional potential of the GBGT1 and GT6m7 in catarrhines. We observed that the purifying selection is prevalent and these genes have a low diversity, though ABO and Ggta1 genes have some sites under positive selection. GT6m7, a putative gene associated with aggressive periodontitis, may have regulatory function, but experimental studies are needed to assess its function. The evolutionary conservation of iGb3S in humans, chimpanzee, and bonobo seems to be the result of proximity to genes with important biological functions.

Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques.

Directory of Open Access Journals (Sweden)

Timothy Carroll

2017-07-01

Full Text Available Zika virus (ZIKV is a mosquito-transmitted virus that can cause severe defects in an infected fetus. ZIKV is also transmitted by sexual contact, although the relative importance of sexual transmission is unclear. To better understand the role of sexual transmission in ZIKV pathogenesis, a nonhuman primate (NHP model of vaginal transmission was developed. ZIKV was readily transmitted to mature cycling female rhesus macaque (RM by vaginal inoculation with 104-106 plaque-forming units (PFU. However, there was variability in susceptibility between the individual RM with 1->8 vaginal inoculations required to establish infection. After treatment with Depoprovera, a widely used contraceptive progestin, two RM that initially resisted 8 vaginal ZIKV inoculations became infected after one ZIKV inoculation. Thus, Depoprovera seemed to enhance susceptibility to vaginal ZIKV transmission. Unexpectedly, the kinetics of virus replication and dissemination after intravaginal ZIKV inoculation were markedly different from RM infected with ZIKV by subcutaneous (SQ virus inoculation. Several groups have reported that after SQ ZIKV inoculation vRNA is rapidly detected in blood plasma with vRNA less common in urine and saliva and only rarely detected in female reproductive tract (FRT secretions. In contrast, in vaginally inoculated RM, plasma vRNA is delayed for several days and ZIKV replication in, and vRNA shedding from, the FRT was found in all 6 animals. Further, after intravaginal transmission ZIKV RNA shedding from FRT secretions was detected before or simultaneously with plasma vRNA, and persisted for at least as long. Thus, ZIKV replication in the FRT was independent of, and often preceded virus replication in the tissues contributing to plasma vRNA. These results support the conclusion that ZIKV preferentially replicates in the FRT after vaginal transmission, but not after SQ transmission, and raise the possibility that there is enhanced fetal infection and

Morphological and functional maturation of Leydig cells: from rodent models to primates.

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Teerds, Katja J; Huhtaniemi, Ilpo T

2015-01-01

Leydig cells (LC) are the sites of testicular androgen production. Development of LC occurs in the testes of most mammalian species as two distinct growth phases, i.e. as fetal and pubertal/adult populations. In primates there are indications of a third neonatal growth phase. LC androgen production begins in embryonic life and is crucial for the intrauterine masculinization of the male fetal genital tract and brain, and continues until birth after which it rapidly declines. A short post-natal phase of LC activity in primates (including human) termed 'mini-puberty' precedes the period of juvenile quiescence. The adult population of LC evolves, depending on species, in mid- to late-prepuberty upon reawakening of the hypothalamic-pituitary-testicular axis, and these cells are responsible for testicular androgen production in adult life, which continues with a slight gradual decline until senescence. This review is an updated comparative analysis of the functional and morphological maturation of LC in model species with special reference to rodents and primates. Pubmed, Scopus, Web of Science and Google Scholar databases were searched between December 2012 and October 2014. Studies published in languages other than English or German were excluded, as were data in abstract form only. Studies available on primates were primarily examined and compared with available data from specific animal models with emphasis on rodents. Expression of different marker genes in rodents provides evidence that at least two distinct progenitor lineages give rise to the fetal LC (FLC) population, one arising from the coelomic epithelium and the other from specialized vascular-associated cells along the gonad-mesonephros border. There is general agreement that the formation and functioning of the FLC population in rodents is gonadotrophin-responsive but not gonadotrophin-dependent. In contrast, although there is in primates some controversy on the role of gonadotrophins in the formation of

Age-associated increase in heterochromatic marks in murine and primate tissues.

Science.gov (United States)

Kreiling, Jill A; Tamamori-Adachi, Mimi; Sexton, Alec N; Jeyapalan, Jessie C; Munoz-Najar, Ursula; Peterson, Abigail L; Manivannan, Jayameenakshi; Rogers, Elizabeth S; Pchelintsev, Nikolay A; Adams, Peter D; Sedivy, John M

2011-04-01

Chromatin is highly dynamic and subject to extensive remodeling under many physiologic conditions. Changes in chromatin that occur during the aging process are poorly documented and understood in higher organisms, such as mammals. We developed an immunofluorescence assay to quantitatively detect, at the single cell level, changes in the nuclear content of chromatin-associated proteins. We found increased levels of the heterochromatin-associated proteins histone macro H2A (mH2A) and heterochromatin protein 1 beta (HP1β) in human fibroblasts during replicative senescence in culture, and for the first time, an age-associated increase in these heterochromatin marks in several tissues of mice and primates. Mouse lung was characterized by monophasic mH2A expression histograms at both ages, and an increase in mean staining intensity at old age. In the mouse liver, we observed increased age-associated localization of mH2A to regions of pericentromeric heterochromatin. In the skeletal muscle, we found two populations of cells with either low or high mH2A levels. This pattern of expression was similar in mouse and baboon, and showed a clear increase in the proportion of nuclei with high mH2A levels in older animals. The frequencies of cells displaying evidence of increased heterochromatinization are too high to be readily accounted for by replicative or oncogene-induced cellular senescence, and are prominently found in terminally differentiated, postmitotic tissues that are not conventionally thought to be susceptible to senescence. Our findings distinguish specific chromatin states in individual cells of mammalian tissues, and provide a foundation to investigate further the progressive epigenetic changes that occur during aging. © 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Facing the facts: The Runx2 gene is associated with variation in facial morphology in primates.

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Ritzman, Terrence B; Banovich, Nicholas; Buss, Kaitlin P; Guida, Jennifer; Rubel, Meagan A; Pinney, Jennifer; Khang, Bao; Ravosa, Matthew J; Stone, Anne C

2017-10-01

The phylogenetic and adaptive factors that cause variation in primate facial form-including differences among the major primate clades and variation related to feeding and/or social behavior-are relatively well understood. However, comparatively little is known about the genetic mechanisms that underlie diversity in facial form in primates. Because it is essential for osteoblastic differentiation and skeletal development, the runt-related transcription factor 2 (Runx2) is one gene that may play a role in these genetic mechanisms. Specifically, polymorphisms in the QA ratio (determined by the ratio of the number of polyglutamines to polyalanines in one functional domain of Runx2) have been shown to be correlated with variation in facial length and orientation in other mammal groups. However, to date, the relationship between variation in this gene and variation in facial form in primates has not been explicitly tested. To test the hypothesis that the QA ratio is correlated with facial form in primates, the current study quantified the QA ratio, facial length, and facial angle in a sample of 33 primate species and tested for correlation using phylogenetic generalized least squares. The results indicate that the QA ratio of the Runx2 gene is positively correlated with variation in relative facial length in anthropoid primates. However, no correlation was found in strepsirrhines, and there was no correlation between facial angle and the QA ratio in any groups. These results suggest that, in primates, the QA ratio of the Runx2 gene may play a role in modulating facial size, but not facial orientation. This study therefore provides important clues about the genetic and developmental mechanisms that may underlie variation in facial form in primates. Copyright © 2017 Elsevier Ltd. All rights reserved.

BCGitis and BCGosis in children with primary immunodeficiency - imaging characteristics

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Shrot, Shai; Soudack, Michalle [Sheba Medical Center, Department of Diagnostic Imaging, Ramat-Gan (Israel); Tel Aviv University, Sackler School of Medicine, Tel Aviv (Israel); Barkai, Galia [Sheba Medical Center, Pediatric Infectious Diseases Unit, Safra Children' s Hospital, Tel-Hashomer (Israel); Ben-Shlush, Aviva [Sheba Medical Center, Department of Diagnostic Imaging, Ramat-Gan (Israel)

2016-02-15

When administered to an immune-compromised patient, BCG (Bacille Calmette-Guerin) can cause disseminated and life-threatening infections. To describe the imaging findings in children with primary immunodeficiency and BCG-related infections. We reviewed the imaging findings of children with primary immunodeficiency treated at a children's hospital during 2012-2014 with localized or disseminated BCG infection. Imaging modalities included US, CT and radiography. Nine children with primary immunodeficiency had clinical signs of post-vaccination BCGitis; seven of these children showed disseminated disease and two showed only regional lesions with characteristic ipsilateral lymphadenopathy. Overall, lymphadenopathy was the most prevalent feature (n = 8) and characteristically appeared as a ring-enhancing hypodense (CT) or hypoechoic (US) lesion. Visceral involvement with multiple abscesses appeared in the spleen (n = 2), liver (n = 1) and bones (n = 1). All lesions regressed following appropriate anti-tuberculosis treatment. BCG infection needs to be considered in children with typical findings and with suspected primary immunodeficiency. (orig.)

Rethinking platelet function: thrombocytopenia induced immunodeficiency in critical illness

DEFF Research Database (Denmark)

Ostrowski, Sisse R; Johansson, Per Ingemar

2011-01-01

Thrombocytopenia in critical illness predicts a poor clinical outcome. Apart from its role in microvascular thrombus formation, it is widely anticipated that this association is indirect rather than causal. Emerging evidence however indicates that platelets are also immune competent cells. Like...... per se results in immunodeficiency through loss of platelet-mediated immune functions, and propose that thrombocytopenia induced immunodeficiency in critical illness in part explain the negative predictive value of low or declining platelet count. We propose that rethinking the risks...... of thrombocytopenia to include not only bleeding but also immunodeficiency and immune dysregulation along with the conduct of studies investigating mechanisms contributing to thrombocytopenia induced poor non-hemorrhagic outcome in critical illness, may be means to improve outcome in these patients through...

Identification of genetic defects in primary immunodeficiencies by whole exome sequencing

DEFF Research Database (Denmark)

Christiansen, Mette; Jensen, Jens Magnus Bernth; Veirum, Jens Erik

2014-01-01

to hypogammaglobulinaemia, and increased risk of both infections as well as cancer. We employed whole exome sequencing (WES) to identify mutations associated with primary immunodeficiency in severely affected children. We present WES data on 2 patients with severe immunodeficiency. WES was performed using TruSeq exome kit...... and severe infections including sepsis. Second, we identified compound heterozygote stopgain mutations in RAD52 and a heterozygote mutation in LRRC8A in a 7 year-old girl with T-cell deficiency, reduced T-cell mediated B-cell activity, hypogammaglobulinaemia, prolonged splenomegali and benign adenopathy. RAD......52 has not previously been linked to immunodeficiency and we are currently investigating the functional consequences. Knowledge of the mechanisms underlying immunodeficiencies is a prerequisite for understanding disease pathogenesis. WES allows the demonstration of immune defects that may result from...

Investigating the dental toolkit of primates based on food mechanical properties: Feeding action does matter.

Science.gov (United States)

Thiery, Ghislain; Guy, Franck; Lazzari, Vincent

2017-06-01

Although conveying an indisputable morphological and behavioral signal, traditional dietary categories such as frugivorous or folivorous tend to group a wide range of food mechanical properties together. Because food/tooth interactions are mostly mechanical, it seems relevant to investigate the dental morphology of primates based on mechanical categories. However, existing mechanical categories classify food by its properties but cannot be used as factors to classify primate dietary habits. This comes from the fact that one primate species might be adapted to a wide range of food mechanical properties. To tackle this issue, what follows is an original framework based on action-related categories. The proposal here is to classify extant primates based on the range of food mechanical properties they can process through one given action. The resulting categories can be used as factors to investigate the dental tools available to primates. Furthermore, cracking, grinding, and shearing categories assigned depending on the hardness and the toughness of food are shown to be supported by morphological data (3D relative enamel thickness) and topographic data (relief index, occlusal complexity, and Dirichlet normal energy). Inferring food mechanical properties from dental morphology is especially relevant for the study of extinct primates, which are mainly documented by dental remains. Hence, we use action-related categories to investigate the molar morphology of an extinct colobine monkey Mesopithecus pentelicus from the Miocene of Pikermi, Greece. Action-related categories show contrasting results compared with classical categories and give us new insights into the dietary adaptations of this extinct primate. Finally, we provide some possible directions for future research aiming to test action-related categories. In particular, we suggest acquiring more data on mechanically challenging fallback foods and advocate the use of other food mechanical properties such as

Feline immunodeficiency. ABCD guidelines on prevention and management.

Science.gov (United States)

Hosie, Margaret J; Addie, Diane; Belák, Sándor; Boucraut-Baralon, Corine; Egberink, Herman; Frymus, Tadeusz; Gruffydd-Jones, Tim; Hartmann, Katrin; Lloret, Albert; Lutz, Hans; Marsilio, Fulvio; Pennisi, Maria Grazia; Radford, Alan D; Thiry, Etienne; Truyen, Uwe; Horzinek, Marian C

2009-07-01

Feline immunodeficiency virus (FIV) is a retrovirus closely related to human immunodeficiency virus. Most felids are susceptible to FIV, but humans are not. Feline immunodeficiency virus is endemic in domestic cat populations worldwide. The virus loses infectivity quickly outside the host and is susceptible to all disinfectants. Feline immunodeficiency virus is transmitted via bites. The risk of transmission is low in households with socially well-adapted cats. Transmission from mother to kittens may occur, especially if the queen is undergoing an acute infection. Cats with FIV are persistently infected in spite of their ability to mount antibody and cell-mediated immune responses. Infected cats generally remain free of clinical signs for several years, and some cats never develop disease, depending on the infecting isolate. Most clinical signs are the consequence of immunodeficiency and secondary infection. Typical manifestations are chronic gingivostomatitis, chronic rhinitis, lymphadenopathy, weight loss and immune-mediated glomerulonephritis. Positive in-practice ELISA results obtained in a low-prevalence or low-risk population should always be confirmed by a laboratory. Western blot is the 'gold standard' laboratory test for FIV serology. PCR-based assays vary in performance. Cats should never be euthanased solely on the basis of an FIV-positive test result. Cats infected with FIV may live as long as uninfected cats, with appropriate management. Asymptomatic FIV-infected cats should be neutered to avoid fighting and virus transmission. Infected cats should receive regular veterinary health checks. They can be housed in the same ward as other patients, but should be kept in individual cages. At present, there is no FIV vaccine commercially available in Europe. Potential benefits and risks of vaccinating FIV-infected cats should be assessed on an individual cat basis. Needles and surgical instruments used on FIV-positive cats may transmit the virus to other cats

Testosterone and reproductive effort in male primates.

Science.gov (United States)

Muller, Martin N

2017-05-01

Considerable evidence suggests that the steroid hormone testosterone mediates major life-history trade-offs in vertebrates, promoting mating effort at the expense of parenting effort or survival. Observations from a range of wild primates support the "Challenge Hypothesis," which posits that variation in male testosterone is more closely associated with aggressive mating competition than with reproductive physiology. In both seasonally and non-seasonally breeding species, males increase testosterone production primarily when competing for fecund females. In species where males compete to maintain long-term access to females, testosterone increases when males are threatened with losing access to females, rather than during mating periods. And when male status is linked to mating success, and dependent on aggression, high-ranking males normally maintain higher testosterone levels than subordinates, particularly when dominance hierarchies are unstable. Trade-offs between parenting effort and mating effort appear to be weak in most primates, because direct investment in the form of infant transport and provisioning is rare. Instead, infant protection is the primary form of paternal investment in the order. Testosterone does not inhibit this form of investment, which relies on male aggression. Testosterone has a wide range of effects in primates that plausibly function to support male competitive behavior. These include psychological effects related to dominance striving, analgesic effects, and effects on the development and maintenance of the armaments and adornments that males employ in mating competition. Copyright © 2016 Elsevier Inc. All rights reserved.

Replicative Intermediates of Human Papillomavirus Type 11 in Laryngeal Papillomas: Site of Replication Initiation and Direction of Replication

Science.gov (United States)

Auborn, K. J.; Little, R. D.; Platt, T. H. K.; Vaccariello, M. A.; Schildkraut, C. L.

1994-07-01

We have examined the structures of replication intermediates from the human papillomavirus type 11 genome in DNA extracted from papilloma lesions (laryngeal papillomas). The sites of replication initiation and termination utilized in vivo were mapped by using neutral/neutral and neutral/alkaline two-dimensional agarose gel electrophoresis methods. Initiation of replication was detected in or very close to the upstream regulatory region (URR; the noncoding, regulatory sequences upstream of the open reading frames in the papillomavirus genome). We also show that replication forks proceed bidirectionally from the origin and converge 180circ opposite the URR. These results demonstrate the feasibility of analysis of replication of viral genomes directly from infected tissue.

The relevance of non-human primate and rodent malaria models for humans

Directory of Open Access Journals (Sweden)

Riley Eleanor

2011-02-01

Full Text Available Abstract At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material.

DNA replication and cancer: From dysfunctional replication origin activities to therapeutic opportunities.

Science.gov (United States)

Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

2016-06-01

A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways to promote genome integrity during DNA replication. This includes suppressing new replication origin firing, stabilization of replicating forks, and the safe restart of forks to prevent any loss of genetic information. Here, we describe mechanisms by which oncogenes can interfere with DNA replication thereby causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gene transfer in rodents and primates as a new tool for modeling diseases in animals and assessing functions by in vivo imaging

Energy Technology Data Exchange (ETDEWEB)

Deglon, N. [Atomic Energy Commission (CEA), Dept. of Medical Research and MIRCen Program, 91 - Orsay (France)

2006-07-01

The identification of disease-causing genes in familial forms of neuro-degenerative disorders and the development of genetic models closely replicating human CNS pathologies have drastically changed our understanding of the molecular events leading to neuronal cell death. If these achievements open new opportunities of therapeutic interventions efficient delivery systems taking into account the specificity of the central nervous system are required to administer therapeutic candidates. In addition, there is a need to develop 1) genetic models in large animals that replicate late stages of the diseases and 2) imaging techniques suitable for longitudinal, quantitative and non-invasive evaluation of disease progression and the evaluation of new therapeutic strategies. Over the last few years, we have investigated the potential of lentiviral vectors as tool to model and treat CNS disorders. The use of lentiviral vectors to create animal model of these pathologies holds various advantages compared to classical transgenic approaches. Viral vectors are versatile, highly flexible tools to perform in vivo studies. Multiple genetic models can be created in a short period of time. High transduction efficiencies as well as robust and sustained trans-gene expression lead to the rapid appearance of functional and behavioral abnormalities and severe neuro-degeneration. Targeted injections in different brain areas can be used to investigate the regional specificity of the neuro-pathology and eliminate potential side effects associated with a widespread over-expression of the trans-gene. Finally, models can be established in different mammalian species including non-human primates, thereby providing an opportunity to assess complex behavioral changes and perform longitudinal follow-up of neuro-pathological alterations by imaging. We have demonstrated the proof of principle of this approach for Huntington's disease. We have shown that the intratriatal injection of lentiviral

Gene transfer in rodents and primates as a new tool for modeling diseases in animals and assessing functions by in vivo imaging

International Nuclear Information System (INIS)

Deglon, N.

2006-01-01

The identification of disease-causing genes in familial forms of neuro-degenerative disorders and the development of genetic models closely replicating human CNS pathologies have drastically changed our understanding of the molecular events leading to neuronal cell death. If these achievements open new opportunities of therapeutic interventions efficient delivery systems taking into account the specificity of the central nervous system are required to administer therapeutic candidates. In addition, there is a need to develop 1) genetic models in large animals that replicate late stages of the diseases and 2) imaging techniques suitable for longitudinal, quantitative and non-invasive evaluation of disease progression and the evaluation of new therapeutic strategies. Over the last few years, we have investigated the potential of lentiviral vectors as tool to model and treat CNS disorders. The use of lentiviral vectors to create animal model of these pathologies holds various advantages compared to classical transgenic approaches. Viral vectors are versatile, highly flexible tools to perform in vivo studies. Multiple genetic models can be created in a short period of time. High transduction efficiencies as well as robust and sustained trans-gene expression lead to the rapid appearance of functional and behavioral abnormalities and severe neuro-degeneration. Targeted injections in different brain areas can be used to investigate the regional specificity of the neuro-pathology and eliminate potential side effects associated with a widespread over-expression of the trans-gene. Finally, models can be established in different mammalian species including non-human primates, thereby providing an opportunity to assess complex behavioral changes and perform longitudinal follow-up of neuro-pathological alterations by imaging. We have demonstrated the proof of principle of this approach for Huntington's disease. We have shown that the intratriatal injection of lentiviral vector

Non-Human Primate Models of Orthopoxvirus Infections

Directory of Open Access Journals (Sweden)

Anne Schmitt

2014-06-01

Full Text Available Smallpox, one of the most destructive diseases, has been successfully eradicated through a worldwide vaccination campaign. Since immunization programs have been stopped, the number of people with vaccinia virus induced immunity is declining. This leads to an increase in orthopoxvirus (OPXV infections in humans, as well as in animals. Additionally, potential abuse of Variola virus (VARV, the causative agent of smallpox, or monkeypox virus, as agents of bioterrorism, has renewed interest in development of antiviral therapeutics and of safer vaccines. Due to its high risk potential, research with VARV is restricted to two laboratories worldwide. Therefore, numerous animal models of other OPXV infections have been developed in the last decades. Non-human primates are especially suitable due to their close relationship to humans. This article provides a review about on non-human primate models of orthopoxvirus infections.

Consensus on context-specific strategies for reducing the stigma of human immunodeficiency virus/acquired immunodeficiency syndrome in Zambézia Province, Mozambique

OpenAIRE

Mukolo, Abraham; Torres, Isabel; Bechtel, Ruth M.; Sidat, Mohsin; Vergara, Alfredo E.

2014-01-01

Stigma has been implicated in poor outcomes of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) care. Reducing stigma is important for HIV prevention and long-term treatment success. Although stigma reduction interventions are conducted in Mozambique, little is known about the current nature of stigma and the efficacy and effectiveness of stigma reduction initiatives. We describe action research to generate consensus on critical characteristics of HIV stigma and an...

Crop damage by primates: quantifying the key parameters of crop-raiding events.

Directory of Open Access Journals (Sweden)

Graham E Wallace

Full Text Available Human-wildlife conflict often arises from crop-raiding, and insights regarding which aspects of raiding events determine crop loss are essential when developing and evaluating deterrents. However, because accounts of crop-raiding behaviour are frequently indirect, these parameters are rarely quantified or explicitly linked to crop damage. Using systematic observations of the behaviour of non-human primates on farms in western Uganda, this research identifies number of individuals raiding and duration of raid as the primary parameters determining crop loss. Secondary factors include distance travelled onto farm, age composition of the raiding group, and whether raids are in series. Regression models accounted for greater proportions of variation in crop loss when increasingly crop and species specific. Parameter values varied across primate species, probably reflecting differences in raiding tactics or perceptions of risk, and thereby providing indices of how comfortable primates are on-farm. Median raiding-group sizes were markedly smaller than the typical sizes of social groups. The research suggests that key parameters of raiding events can be used to measure the behavioural impacts of deterrents to raiding. Furthermore, farmers will benefit most from methods that discourage raiding by multiple individuals, reduce the size of raiding groups, or decrease the amount of time primates are on-farm. This study demonstrates the importance of directly relating crop loss to the parameters of raiding events, using systematic observations of the behaviour of multiple primate species.

Crop Damage by Primates: Quantifying the Key Parameters of Crop-Raiding Events

Science.gov (United States)

Wallace, Graham E.; Hill, Catherine M.

2012-01-01

Human-wildlife conflict often arises from crop-raiding, and insights regarding which aspects of raiding events determine crop loss are essential when developing and evaluating deterrents. However, because accounts of crop-raiding behaviour are frequently indirect, these parameters are rarely quantified or explicitly linked to crop damage. Using systematic observations of the behaviour of non-human primates on farms in western Uganda, this research identifies number of individuals raiding and duration of raid as the primary parameters determining crop loss. Secondary factors include distance travelled onto farm, age composition of the raiding group, and whether raids are in series. Regression models accounted for greater proportions of variation in crop loss when increasingly crop and species specific. Parameter values varied across primate species, probably reflecting differences in raiding tactics or perceptions of risk, and thereby providing indices of how comfortable primates are on-farm. Median raiding-group sizes were markedly smaller than the typical sizes of social groups. The research suggests that key parameters of raiding events can be used to measure the behavioural impacts of deterrents to raiding. Furthermore, farmers will benefit most from methods that discourage raiding by multiple individuals, reduce the size of raiding groups, or decrease the amount of time primates are on-farm. This study demonstrates the importance of directly relating crop loss to the parameters of raiding events, using systematic observations of the behaviour of multiple primate species. PMID:23056378

Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina.

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Peter Charbel Issa

Full Text Available Adeno-associated viral vectors (AAV have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of different rAAV serotypes isolated from primate brain were combined to create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy of these novel serotypes were assessed in wild type mice and in two models of retinal degeneration (the Abca4(-/- mouse which is a model for Stargardt disease and in the Pde6b(rd1/rd1 mouse in vivo, in primate tissue ex-vivo, and in the human-derived SH-SY5Y cell line, using an identical AAV2 expression cassette. We show that these novel hybrid serotypes can transduce retinal tissue in mice and primates efficiently, although no more than AAV2/2 and rAAV2/5 serotypes. Transduction efficiency appeared lower in the Abca4(-/- mouse compared to wild type with all vectors tested, suggesting an effect of specific retinal diseases on the efficiency of gene delivery. Shuffling of AAV capsid domains may have clinical applications for patients who develop T-cell immune responses following AAV gene therapy, as specific peptide antigen sequences could be substituted using this technique prior to vector re-treatments.

Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina.

Science.gov (United States)

Charbel Issa, Peter; De Silva, Samantha R; Lipinski, Daniel M; Singh, Mandeep S; Mouravlev, Alexandre; You, Qisheng; Barnard, Alun R; Hankins, Mark W; During, Matthew J; Maclaren, Robert E

2013-01-01

Adeno-associated viral vectors (AAV) have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of different rAAV serotypes isolated from primate brain were combined to create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy of these novel serotypes were assessed in wild type mice and in two models of retinal degeneration (the Abca4(-/-) mouse which is a model for Stargardt disease and in the Pde6b(rd1/rd1) mouse) in vivo, in primate tissue ex-vivo, and in the human-derived SH-SY5Y cell line, using an identical AAV2 expression cassette. We show that these novel hybrid serotypes can transduce retinal tissue in mice and primates efficiently, although no more than AAV2/2 and rAAV2/5 serotypes. Transduction efficiency appeared lower in the Abca4(-/-) mouse compared to wild type with all vectors tested, suggesting an effect of specific retinal diseases on the efficiency of gene delivery. Shuffling of AAV capsid domains may have clinical applications for patients who develop T-cell immune responses following AAV gene therapy, as specific peptide antigen sequences could be substituted using this technique prior to vector re-treatments.

Identification of Plasmodium spp. in Neotropical primates of Maranhense Amazon in Northeast Brazil.

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Mayra Araguaia Pereira Figueiredo

Full Text Available In the Brazilian Amazon region, malaria caused by Plasmodium malariae is considered to be a zoonosis because of cross-transfer of the parasite between humans and Neotropical primates. To contribute information on this issue, we investigated occurrences of natural infection with Plasmodium sp. among Neotropical primates in the Maranhense Amazon (Amazon region of the state of Maranhão, in the northeastern region of Brazil. Blood samples were collected from 161 Neotropical primates of six species that were caught in an environmental reserve (Sítio Aguahy and from captive primates (CETAS-Wildlife Screening Center, municipality of São Luís, in Maranhão. Plasmodium sp. was diagnosed based on light microscopy, PCR, qPCR and LAMP for amplification of the 18S rRNA gene. Serum samples were also assayed by means of indirect immunofluorescence for IgG antibodies against P. malariae/P. brasilianum, P. falciparum and P. berghei. Parasites were detected through light microscopy on five slides from captive primates (four Sapajus spp. and one Callithrix jacchus. In the molecular tests, 34.16% (55/161 and 29.81% (48/161 of the animals sampled were positive in the qPCR and PCR assays, respectively. In the PCR, 47/48 animals were positive for P. malariae/P. brasilianum; of these, eight were free-living primates and 39 from CETAS, São Luís. One sample showed a band in the genus-specific reaction, but not in the second PCR reaction. Anti-P. malariae/P. brasilianum IgG antibodies were detected in four serum samples from Sapajus spp. in captivity. In this study, circulation of P. malariae/P. brasilianum in Neotropical primates was confirmed, with low levels of parasitemia and low levels of antibodies. The importance of these animals as reservoirs of human malaria in the region studied is still unknown. This scenario has an impact on control and elimination of malaria in this region.

Feline Immunodeficiency Virus Evolutionarily Acquires Two Proteins, Vif and Protease, Capable of Antagonizing Feline APOBEC3.

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Yoshikawa, Rokusuke; Takeuchi, Junko S; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Kimura, Yuichi; Ren, Fengrong; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei

2017-06-01

The interplay between viral and host proteins has been well studied to elucidate virus-host interactions and their relevance to virulence. Mammalian genes encode apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins, which act as intrinsic restriction factors against lentiviruses. To overcome APOBEC3-mediated antiviral actions, lentiviruses have evolutionarily acquired an accessory protein, viral infectivity factor (Vif), and Vif degrades host APOBEC3 proteins via a ubiquitin/proteasome-dependent pathway. Although the Vif-APOBEC3 interaction and its evolutionary significance, particularly those of primate lentiviruses (including HIV) and primates (including humans), have been well investigated, those of nonprimate lentiviruses and nonprimates are poorly understood. Moreover, the factors that determine lentiviral pathogenicity remain unclear. Here, we focus on feline immunodeficiency virus (FIV), a pathogenic lentivirus in domestic cats, and the interaction between FIV Vif and feline APOBEC3 in terms of viral virulence and evolution. We reveal the significantly reduced diversity of FIV subtype B compared to that of other subtypes, which may associate with the low pathogenicity of this subtype. We also demonstrate that FIV subtype B Vif is less active with regard to feline APOBEC3 degradation. More intriguingly, we further reveal that FIV protease cleaves feline APOBEC3 in released virions. Taken together, our findings provide evidence that a lentivirus encodes two types of anti-APOBEC3 factors, Vif and viral protease. IMPORTANCE During the history of mammalian evolution, mammals coevolved with retroviruses, including lentiviruses. All pathogenic lentiviruses, excluding equine infectious anemia virus, have acquired the vif gene via evolution to combat APOBEC3 proteins, which are intrinsic restriction factors against exogenous lentiviruses. Here we demonstrate that FIV, a pathogenic lentivirus in domestic cats, antagonizes feline APOBEC3

Conservation strategies for understanding and combating the primate bushmeat trade on Bioko Island, Equatorial Guinea.

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Cronin, Drew T; Sesink Clee, Paul R; Mitchell, Matthew W; Bocuma Meñe, Demetrio; Fernández, David; Riaco, Cirilo; Fero Meñe, Maximiliano; Esara Echube, Jose Manuel; Hearn, Gail W; Gonder, Mary Katherine

2017-11-01

Bioko Island, Equatorial Guinea is among the important places in Africa for the conservation of primates, but a cultural preference for bushmeat and a lack of effective law enforcement has encouraged commercial bushmeat hunting, threatening the survival of the remaining primate population. For over 13 years, we collected bushmeat market data in the Malabo market, recording over 35,000 primate carcasses, documenting "mardi gras" consumption patterns, seasonal carcass availability, and negative effects resulting from government intervention. We also conducted forest surveys throughout Bioko's two protected areas in order to localize and quantify primate populations and hunting pressure. Using these data, we were able to document the significant negative impact bushmeat hunting had on monkey populations, estimate which species are most vulnerable to hunting, and develop ecological niche models to approximate the distribution of each of Bioko's diurnal primate species. These results also have allowed for the identification of primate hotspots, such as the critically important southwest region of the Gran Caldera Scientific Reserve, and thus, priority areas for conservation on Bioko, leading to more comprehensive conservation recommendations. Current and future efforts now focus on bridging the gap between investigators and legislators in order to develop and effectively implement a management plan for Bioko's Gran Caldera Scientific Reserve and to develop a targeted educational campaign to reduce demand by changing consumer attitudes toward bushmeat. Using this multidisciplinary approach, informed by biological, socioeconomic, and cultural research, there may yet be a positive future for the primates of Bioko. © 2017 Wiley Periodicals, Inc.

Allelic lineages of the ficolin genes (FCNs are passed from ancestral to descendant primates.

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Tina Hummelshøj

Full Text Available The ficolins recognize carbohydrates and acetylated compounds on microorganisms and dying host cells and are able to activate the lectin pathway of the complement system. In humans, three ficolin genes have been identified: FCN1, FCN2 and FCN3, which encode ficolin-1, ficolin-2 and ficolin-3, respectively. Rodents have only two ficolins designated ficolin-A and ficolin-B that are closely related to human ficolin-1, while the rodent FCN3 orthologue is a pseudogene. Ficolin-2 and ficolin-3 have so far only been observed in humans. Thus, we performed a systematic investigation of the FCN genes in non-human primates. The exons and intron-exon boundaries of the FCN1-3 genes were sequenced in the following primate species: chimpanzee, gorilla, orangutan, rhesus macaque, cynomolgus macaque, baboon and common marmoset. We found that the exon organisation of the FCN genes was very similar between all the non-human primates and the human FCN genes. Several variations in the FCN genes were found in more than one primate specie suggesting that they were carried from one species to another including humans. The amino acid diversity of the ficolins among human and non-human primate species was estimated by calculating the Shannon entropy revealing that all three proteins are generally highly conserved. Ficolin-1 and ficolin-2 showed the highest diversity, whereas ficolin-3 was more conserved. Ficolin-2 and ficolin-3 were present in non-human primate sera with the same characteristic oligomeric structures as seen in human serum. Taken together all the FCN genes show the same characteristics in lower and higher primates. The existence of trans-species polymorphisms suggests that different FCN allelic lineages may be passed from ancestral to descendant species.

Primates decline rapidly in unprotected forests: evidence from a monitoring program with data constraints.

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Rovero, Francesco; Mtui, Arafat; Kitegile, Amani; Jacob, Philipo; Araldi, Alessandro; Tenan, Simone

2015-01-01

Growing threats to primates in tropical forests make robust and long-term population abundance assessments increasingly important for conservation. Concomitantly, monitoring becomes particularly relevant in countries with primate habitat. Yet monitoring schemes in these countries often suffer from logistic constraints and/or poor rigor in data collection, and a lack of consideration of sources of bias in analysis. To address the need for feasible monitoring schemes and flexible analytical tools for robust trend estimates, we analyzed data collected by local technicians on abundance of three species of arboreal monkey in the Udzungwa Mountains of Tanzania (two Colobus species and one Cercopithecus), an area of international importance for primate endemism and conservation. We counted primate social groups along eight line transects in two forest blocks in the area, one protected and one unprotected, over a span of 11 years. We applied a recently proposed open metapopulation model to estimate abundance trends while controlling for confounding effects of observer, site, and season. Primate populations were stable in the protected forest, while the colobines, including the endemic Udzungwa red colobus, declined severely in the unprotected forest. Targeted hunting pressure at this second site is the most plausible explanation for the trend observed. The unexplained variability in detection probability among transects was greater than the variability due to observers, indicating consistency in data collection among observers. There were no significant differences in both primate abundance and detectability between wet and dry seasons, supporting the choice of sampling during the dry season only based on minimizing practical constraints. Results show that simple monitoring routines implemented by trained local technicians can effectively detect changes in primate populations in tropical countries. The hierarchical Bayesian model formulation adopted provides a flexible

Organising pneumonia in common variable immunodeficiency.

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Boujaoude, Ziad; Arya, Rohan; Rafferty, William; Dammert, Pedro

2013-06-07

Common variable immunodeficiency (CVID) is the most common of the primary immunodeficiency disorders. Pulmonary manifestations are characterised by recurrent rhinosinusitis, respiratory tract infections and bronchiectasis. Less commonly the lung may be affected by lymphoid disorders and sarcoid-like granulomas. Organising pneumonia (OP) is a rare pulmonary manifestation. We report the case of a 32-year-old woman with CVID who presented with fever, dyspnoea and persistent lung infiltrates despite antibiotic therapy. CT of the chest showed bilateral patchy alveolar infiltrates. Pulmonary function tests revealed moderate restriction and reduction in diffusion capacity. Initial bronchoscopy with transbronchial biopsies did not yield a diagnosis but surgical lung biopsies identified OP. Significant clinical, radiographic and physiological improvement was achieved after institution of corticosteroid therapy.

Los cromosomas sexuales en los Primates no sólo son X e Y

OpenAIRE

Steinberg, María Eugenia; Nieves, Mariela; Mudry, Marta Dolores

2009-01-01

En el Orden Primates se agrupan dos subórdenes, Strepsirrhini y Haplorrhini, donde las formas actuales del segundo comprenden a los Tarsiiformes junto a los Primates del Nuevo (Platyrrhini) y del Viejo Mundo (Catarrhini), incluyendo a Hominoidea en los últimos. En estos mamíferos el sistema de determinación sexual más extendido es el XX/XY, tal como se ha descrito en los Primates del Viejo Mundo, incluidos los humanos, de ahí el nombre de "human like". En los Platyrrhini actuales se observa l...

Nonhuman primates prefer slow tempos but dislike music overall.

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McDermott, Josh; Hauser, Marc D

2007-09-01

Human adults generally find fast tempos more arousing than slow tempos, with tempo frequently manipulated in music to alter tension and emotion. We used a previously published method [McDermott, J., & Hauser, M. (2004). Are consonant intervals music to their ears? Spontaneous acoustic preferences in a nonhuman primate. Cognition, 94(2), B11-B21] to test cotton-top tamarins and common marmosets, two new-World primates, for their spontaneous responses to stimuli that varied systematically with respect to tempo. Across several experiments, we found that both tamarins and marmosets preferred slow tempos to fast. It is possible that the observed preferences were due to arousal, and that this effect is homologous to the human response to tempo. In other respects, however, these two monkey species showed striking differences compared to humans. Specifically, when presented with a choice between slow tempo musical stimuli, including lullabies, and silence, tamarins and marmosets preferred silence whereas humans, when similarly tested, preferred music. Thus despite the possibility of homologous mechanisms for tempo perception in human and nonhuman primates, there appear to be motivational ties to music that are uniquely human.

Evaluation of Clinical and Laboratory Data in Patients with Recurrent Infections and Suspected Immunodeficiency

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Hamid Ahanchian

2014-09-01

Full Text Available Background: Frequent infections is among the most frequent clinical dilemmas for primary care physicians. Immunodeficiency disorders are a heterogeneous group of illnesses that predispose patients to the recurrent infections, autoimmunity and malignancies. The aim of this study was to evaluate the clinical and laboratory data collected for the final diagnosis of patients referred with recurrent infections and suspected immunodeficiency to a local immunodeficiency clinic.   Methods: This epidemiological study was carried out between April 2010 and September 2012 at the Immunodeficiency Clinic of Mashhad. All patients with clinical manifestations of immunodeficiency who were referred to our clinic during this period of time were included in this study. 41 patients aged from 10 months to 51 years, were evaluated. Results: Forty one patients, aged between 10 months and 51 years were evaluated. Eleven patients had a primary immunodeficiency, four cases had a secondary immunodeficiency, in three patients an underlying structural disease were found, eight patients were predisposed to recurrent infections as a result of allergies and finally, fifteen cases were found to be normal individuals.   Discussion: Most patients with recurrent infection have a normal immune system. Allergic disorders are the most common predisposing factor to recurrent infection. However, as immunodeficiency disorders are potentially serious, early diagnosis can improve the quality of life and outcome and prevent severe sequels in future.

Crying tapir: the functionality of errors and accuracy in predator recognition in two neotropical high-canopy primates.

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Mourthé, Ítalo; Barnett, Adrian A

2014-01-01

Predation is often considered to be a prime driver in primate evolution, but, as predation is rarely observed in nature, little is known of primate antipredator responses. Time-limited primates should be highly discerning when responding to predators, since time spent in vigilance and avoidance behaviour may supplant other activities. We present data from two independent studies describing and quantifying the frequency, nature and duration of predator-linked behaviours in 2 high-canopy primates, Ateles belzebuth and Cacajao ouakary. We introduce the concept of 'pseudopredators' (harmless species whose appearance is sufficiently similar to that of predators to elicit antipredator responses) and predict that changes in behaviour should increase with risk posed by a perceived predator. We studied primate group encounters with non-primate vertebrates across 14 (Ateles) and 19 (Cacajao) months in 2 undisturbed Amazonian forests. Although preliminary, data on both primates revealed that they distinguished the potential predation capacities of other species, as predicted. They appeared to differentiate predators from non-predators and distinguished when potential predators were not an immediate threat, although they reacted erroneously to pseudopredators, on average in about 20% of the responses given toward other vertebrates. Reacting to pseudopredators would be interesting since, in predation, one error can be fatal to the prey. © 2015 S. Karger AG, Basel.

Deep Hierarchies in the Primate Visual Cortex

DEFF Research Database (Denmark)

Krüger, Norbert; Jannsen, Per; Kalkan, S.

2013-01-01

Computational modeling of the primate visual system yields insights of potential relevance to some of the challenges that computer vision is facing, such as object recognition and categorization, motion detection and activity recognition or vision-based navigation and manipulation. This article r...

Primate Innovation: Sex, Age and Social Rank

NARCIS (Netherlands)

Reader, S.M.; Laland, K.N.

2001-01-01

Analysis of an exhaustive survey of primate behavior collated from the published literature revealed significant variation in rates of innovation among individuals of different sex, age and social rank. We searched approximately 1,000 articles in four primatology journals, together with other

Molecular phylogeny of anoplocephalid tapeworms (Cestoda: Anoplocephalidae) infecting humans and non-human primates.

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Doležalová, Jana; Vallo, Peter; Petrželková, Klára J; Foitová, Ivona; Nurcahyo, Wisnu; Mudakikwa, Antoine; Hashimoto, Chie; Jirků, Milan; Lukeš, Julius; Scholz, Tomáš; Modrý, David

2015-09-01

Anoplocephalid tapeworms of the genus Bertiella Stiles and Hassall, 1902 and Anoplocephala Blanchard, 1848, found in the Asian, African and American non-human primates are presumed to sporadic ape-to-man transmissions. Variable nuclear (5.8S-ITS2; 28S rRNA) and mitochondrial genes (cox1; nad1) of isolates of anoplocephalids originating from different primates (Callicebus oenanthe, Gorilla beringei, Gorilla gorilla, Pan troglodytes and Pongo abelii) and humans from various regions (South America, Africa, South-East Asia) were sequenced. In most analyses, Bertiella formed a monophyletic group within the subfamily Anoplocephalinae, however, the 28S rRNA sequence-based analysis indicated paraphyletic relationship between Bertiella from primates and Australian marsupials and rodents, which should thus be regarded as different taxa. Moreover, isolate determined as Anoplocephala cf. gorillae from mountain gorilla clustered within the Bertiella clade from primates. This either indicates that A. gorillae deserves to be included into the genus Bertiella, or, that an unknown Bertiella species infects also mountain gorillas. The analyses allowed the genetic differentiation of the isolates, albeit with no obvious geographical or host-related patterns. The unexpected genetic diversity of the isolates studied suggests the existence of several Bertiella species in primates and human and calls for revision of the whole group, based both on molecular and morphological data.

Social network analysis in the study of nonhuman primates: A historical perspective

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Brent, Lauren J.N.; Lehmann, Julia; Ramos-Fernández, Gabriel

2011-01-01

Advances over the last fifteen years have made social network analysis (SNA) a powerful tool for the study of nonhuman primate social behavior. Although many SNA-based techniques have been only very recently adopted in primatological research, others have been commonly used by primatologists for decades. The roots of SNA also stem from some of the same conceptual frameworks as the majority of nonhuman primate behavioral research. The rapid development of SNA in recent years has led to questions within the primatological community of where and how SNA fits within this field. We aim to address these questions by providing an overview of the historical relationship between SNA and the study of nonhuman primates. We begin with a brief history of the development of SNA, followed by a detailed description of the network-based visualization techniques, analytical methods and conceptual frameworks which have been employed by primatologists since as early as the 1960s. We also introduce some of the latest advances to SNA, thereby demonstrating that this approach contains novel tools for study of nonhuman primate social behavior which may be used to shed light on questions that cannot be addressed fully using more conventional methods. PMID:21433047

Long-distance transportation of primate embryos developing in culture: a preliminary study.

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Nichols, Stephanie; Harvey, Alexandra; Gierbolini, Lynette; Gonzalez-Martinez, Janis; Brenner, Carol; Bavister, Barry

2010-03-01

Non-human primate embryos are invaluable for conducting research relevant to human infertility and stem cells, but their availability is restricted. In this preliminary study, rhesus monkey embryos were produced by IVF at the Caribbean Primate Research Centre and shipped in tubes of gassed culture medium within a battery-powered transport incubator by overnight courier to Wayne State University in Michigan. Upon arrival, the embryos were incubated in fresh culture medium to evaluate further development. In 11 shipments comprising 98 cleavage-stage embryos developing from oocytes that were mature (MII) upon collection, 51 (52%) reached advanced preimplantation stages (morula to hatched blastocyst) during prolonged culture following transportation. However, most embryos produced from oocytes that were immature (MI) at collection arrested and only 5/51 (10%) reached advanced stages of development. This study demonstrates that non-cryopreserved primate embryos can be routinely transported between distant sites without loss of developmental ability. In this way, the processes of production and study of non-cryopreserved primate embryos need not be restricted to the same or nearby laboratories. This will expand the use of these embryos for research and facilitate generation of translationally relevant information. Published by Elsevier Ltd.

Structural analysis of a repetitive protein sequence motif in strepsirrhine primate amelogenin.

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Rodrigo S Lacruz

2011-03-01

Full Text Available Strepsirrhines are members of a primate suborder that has a distinctive set of features associated with the development of the dentition. Amelogenin (AMEL, the better known of the enamel matrix proteins, forms 90% of the secreted organic matrix during amelogenesis. Although AMEL has been sequenced in numerous mammalian lineages, the only reported strepsirrhine AMEL sequences are those of the ring-tailed lemur and galago, which contain a set of additional proline-rich tandem repeats absent in all other primates species analyzed to date, but present in some non-primate mammals. Here, we first determined that these repeats are present in AMEL from three additional lemur species and thus are likely to be widespread throughout this group. To evaluate the functional relevance of these repeats in strepsirrhines, we engineered a mutated murine amelogenin sequence containing a similar proline-rich sequence to that of Lemur catta. In the monomeric form, the MQP insertions had no influence on the secondary structure or refolding properties, whereas in the assembled form, the insertions increased the hydrodynamic radii. We speculate that increased AMEL nanosphere size may influence enamel formation in strepsirrhine primates.

Curing Color Blindness—Mice and Nonhuman Primates

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Neitz, Maureen; Neitz, Jay

2014-01-01

It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates, red-green color vision in mice is poor, indicating large differences between mice and monkeys in their ability to take advantage of the new input. These results have implications for understanding the limits and opportunities for using gene therapy to treat vision disorders caused by defects in cone function. PMID:25147187

Patterns of variation across primates in jaw-muscle electromyography during mastication.

Science.gov (United States)

Vinyard, Christopher J; Wall, Christine E; Williams, Susan H; Hylander, William L

2008-08-01

Biologists that study mammals continue to discuss the evolution of and functional variation in jaw-muscle activity during chewing. A major barrier to addressing these issues is collecting sufficient in vivo data to adequately capture neuromuscular variation in a clade. We combine data on jaw-muscle electromyography (EMG) collected during mastication from 14 species of primates and one of treeshrews to assess patterns of neuromuscular variation in primates. All data were collected and analyzed using the same methods. We examine the variance components for EMG parameters using a nested ANOVA design across successive hierarchical factors from chewing cycle through species for eight locations in the masseter and temporalis muscles. Variation in jaw-muscle EMGs was not distributed equally across hierarchical levels. The timing of peak EMG activity showed the largest variance components among chewing cycles. Relative levels of recruitment of jaw muscles showed the largest variance components among chewing sequences and cycles. We attribute variation among chewing cycles to (1) changes in food properties throughout the chewing sequence, (2) variation in bite location, and (3) the multiple ways jaw muscles can produce submaximal bite forces. We hypothesize that variation among chewing sequences is primarily related to variation in properties of food. The significant proportion of variation in EMGs potentially linked to food properties suggests that experimental biologists must pay close attention to foods given to research subjects in laboratory-based studies of feeding. The jaw muscles exhibit markedly different variance components among species suggesting that primate jaw muscles have evolved as distinct functional units. The balancing-side deep masseter (BDM) exhibits the most variation among species. This observation supports previous hypotheses linking variation in the timing and activation of the BDM to symphyseal fusion in anthropoid primates and in strepsirrhines

Repair replication in replicating and nonreplicating DNA after irradiation with uv light

Energy Technology Data Exchange (ETDEWEB)

Slor, H.; Cleaver, J.E.

1978-06-01

Ultraviolet light induces more pyrimidine dimers and more repair replication in DNA that replicates within 2 to 3 h of irradiation than in DNA that does not replicate during this period. This difference may be due to special conformational changes in DNA and chromatin that might be associated with semiconservative DNA replication.

'Omics investigations of HIV and SIV pathogenesis and innate immunity.

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Palermo, Robert E; Fuller, Deborah H

2013-01-01

In the 30 years since the advent of the AIDS epidemic, the biomedical community has put forward a battery of molecular therapies that are based on the accumulated knowledge of a limited number of viral targets. Despite these accomplishments, the community still confronts unanswered foundational questions about HIV infection. What are the cellular or biomolecular processes behind HIV pathogenesis? Can we elucidate the characteristics that distinguish those individuals who are naturally resistant to either infection or disease progression? The discovery of simian immunodeficiency viruses (SIVs) and the ensuing development of in vivo, nonhuman primate (NHP) infection models was a tremendous advance, especially in abetting the exploration of vaccine strategies. And while there have been numerous NHP infection models and vaccine trials performed, fundamental questions remain regarding host-virus interactions and immune correlates of protection. These issues are, perhaps, most starkly illustrated with the appreciation that many species of African nonhuman primates are naturally infected with strains of SIV that do not cause any appreciable disease while replicating to viral loads that match or exceed those seen with pathogenic SIV infections in Asian species of nonhuman primates. The last decade has seen the establishment of high-throughput molecular profiling tools, such as microarrays for transcriptomics, SNP arrays for genome features, and LC-MS techniques for proteins or metabolites. These provide the capacity to interrogate a biological model at a comprehensive, systems level, in contrast to historical approaches that characterized a few genes or proteins in an experiment. These methods have already had revolutionary impacts in understanding human diseases originating within the host genome such as genetic disorders and cancer, and the methods are finding increasing application in the context of infectious disease. We will provide a review of the use of such 'omics

A solution to the worn tooth conundrum in primate functional anatomy

OpenAIRE

Ungar, Peter S.; M'Kirera, Francis

2003-01-01

Worn teeth are a bane to paleobiologists interested in the diets of human ancestors and other fossil primates. Although worn teeth dominate fossil assemblages, their shapes are usually not used to reconstruct the diets of extinct species. The problem is that traditional studies of primate dental functional anatomy have focused on unworn morphology. This has limited most functional analyses to only a few well-represented fossil species. This paper introduces a method to characterize and compar...

Screening for Human Immunodeficiency Virus (HIV)

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... with antiretroviral therapy (ART). Starting ART early—before symptoms appear—greatly reduces the risk of developing acquired immunodeficiency syndrome (AIDS, the final stage of HIV infection), having AIDS-related complications, or dying of ...

Common Variable Immunodeficiency: Diagnosis, Management, and Treatment.

Science.gov (United States)

Abbott, Jordan K; Gelfand, Erwin W

2015-11-01

Common variable immunodeficiency (CVID) refers to a grouping of antibody deficiencies that lack a more specific genetic or phenotypic classification. It is the immunodeficiency classification with the greatest number of constituents, likely because of the numerous ways in which antibody production can be impaired and the frequency in which antibody production becomes impaired in human beings. CVID comprises a heterogeneous group of rare diseases. Consequently, CVID presents a significant challenge for researchers and clinicians. Despite these difficulties, both our understanding of and ability to manage this grouping of complex immune diseases has advanced significantly over the past 60 years. Copyright © 2015 Elsevier Inc. All rights reserved.

Silencing, positive selection and parallel evolution: busy history of primate cytochromes C.

Science.gov (United States)

Pierron, Denis; Opazo, Juan C; Heiske, Margit; Papper, Zack; Uddin, Monica; Chand, Gopi; Wildman, Derek E; Romero, Roberto; Goodman, Morris; Grossman, Lawrence I

2011-01-01

Cytochrome c (cyt c) participates in two crucial cellular processes, energy production and apoptosis, and unsurprisingly is a highly conserved protein. However, previous studies have reported for the primate lineage (i) loss of the paralogous testis isoform, (ii) an acceleration and then a deceleration of the amino acid replacement rate of the cyt c somatic isoform, and (iii) atypical biochemical behavior of human cyt c. To gain insight into the cause of these major evolutionary events, we have retraced the history of cyt c loci among primates. For testis cyt c, all primate sequences examined carry the same nonsense mutation, which suggests that silencing occurred before the primates diversified. For somatic cyt c, maximum parsimony, maximum likelihood, and Bayesian phylogenetic analyses yielded the same tree topology. The evolutionary analyses show that a fast accumulation of non-synonymous mutations (suggesting positive selection) occurred specifically on the anthropoid lineage root and then continued in parallel on the early catarrhini and platyrrhini stems. Analysis of evolutionary changes using the 3D structure suggests they are focused on the respiratory chain rather than on apoptosis or other cyt c functions. In agreement with previous biochemical studies, our results suggest that silencing of the cyt c testis isoform could be linked with the decrease of primate reproduction rate. Finally, the evolution of cyt c in the two sister anthropoid groups leads us to propose that somatic cyt c evolution may be related both to COX evolution and to the convergent brain and body mass enlargement in these two anthropoid clades.

Silencing, positive selection and parallel evolution: busy history of primate cytochromes C.

Directory of Open Access Journals (Sweden)

Denis Pierron

Full Text Available Cytochrome c (cyt c participates in two crucial cellular processes, energy production and apoptosis, and unsurprisingly is a highly conserved protein. However, previous studies have reported for the primate lineage (i loss of the paralogous testis isoform, (ii an acceleration and then a deceleration of the amino acid replacement rate of the cyt c somatic isoform, and (iii atypical biochemical behavior of human cyt c. To gain insight into the cause of these major evolutionary events, we have retraced the history of cyt c loci among primates. For testis cyt c, all primate sequences examined carry the same nonsense mutation, which suggests that silencing occurred before the primates diversified. For somatic cyt c, maximum parsimony, maximum likelihood, and Bayesian phylogenetic analyses yielded the same tree topology. The evolutionary analyses show that a fast accumulation of non-synonymous mutations (suggesting positive selection occurred specifically on the anthropoid lineage root and then continued in parallel on the early catarrhini and platyrrhini stems. Analysis of evolutionary changes using the 3D structure suggests they are focused on the respiratory chain rather than on apoptosis or other cyt c functions. In agreement with previous biochemical studies, our results suggest that silencing of the cyt c testis isoform could be linked with the decrease of primate reproduction rate. Finally, the evolution of cyt c in the two sister anthropoid groups leads us to propose that somatic cyt c evolution may be related both to COX evolution and to the convergent brain and body mass enlargement in these two anthropoid clades.

Inactivation of Primate Prefrontal Cortex Impairs Auditory and Audiovisual Working Memory.

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Plakke, Bethany; Hwang, Jaewon; Romanski, Lizabeth M

2015-07-01

The prefrontal cortex is associated with cognitive functions that include planning, reasoning, decision-making, working memory, and communication. Neurophysiology and neuropsychology studies have established that dorsolateral prefrontal cortex is essential in spatial working memory while the ventral frontal lobe processes language and communication signals. Single-unit recordings in nonhuman primates has shown that ventral prefrontal (VLPFC) neurons integrate face and vocal information and are active during audiovisual working memory. However, whether VLPFC is essential in remembering face and voice information is unknown. We therefore trained nonhuman primates in an audiovisual working memory paradigm using naturalistic face-vocalization movies as memoranda. We inactivated VLPFC, with reversible cortical cooling, and examined performance when faces, vocalizations or both faces and vocalization had to be remembered. We found that VLPFC inactivation impaired subjects' performance in audiovisual and auditory-alone versions of the task. In contrast, VLPFC inactivation did not disrupt visual working memory. Our studies demonstrate the importance of VLPFC in auditory and audiovisual working memory for social stimuli but suggest a different role for VLPFC in unimodal visual processing. The ventral frontal lobe, or inferior frontal gyrus, plays an important role in audiovisual communication in the human brain. Studies with nonhuman primates have found that neurons within ventral prefrontal cortex (VLPFC) encode both faces and vocalizations and that VLPFC is active when animals need to remember these social stimuli. In the present study, we temporarily inactivated VLPFC by cooling the cortex while nonhuman primates performed a working memory task. This impaired the ability of subjects to remember a face and vocalization pair or just the vocalization alone. Our work highlights the importance of the primate VLPFC in the processing of faces and vocalizations in a manner that

Evolution and Allometry of Calcaneal Elongation in Living and Extinct Primates

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Boyer, Doug M.; Seiffert, Erik R.; Gladman, Justin T.; Bloch, Jonathan I.

2013-01-01

Specialized acrobatic leaping has been recognized as a key adaptive trait tied to the origin and subsequent radiation of euprimates based on its observed frequency in extant primates and inferred frequency in extinct early euprimates. Hypothesized skeletal correlates include elongated tarsal elements, which would be expected to aid leaping by allowing for increased rates and durations of propulsive acceleration at takeoff. Alternatively, authors of a recent study argued that pronounced distal calcaneal elongation of euprimates (compared to other mammalian taxa) was related primarily to specialized pedal grasping. Testing for correlations between calcaneal elongation and leaping versus grasping is complicated by body size differences and associated allometric affects. We re-assess allometric constraints on, and the functional significance of, calcaneal elongation using phylogenetic comparative methods, and present an evolutionary hypothesis for the evolution of calcaneal elongation in primates using a Bayesian approach to ancestral state reconstruction (ASR). Results show that among all primates, logged ratios of distal calcaneal length to total calcaneal length are inversely correlated with logged body mass proxies derived from the area of the calcaneal facet for the cuboid. Results from phylogenetic ANOVA on residuals from this allometric line suggest that deviations are explained by degree of leaping specialization in prosimians, but not anthropoids. Results from ASR suggest that non-allometric increases in calcaneal elongation began in the primate stem lineage and continued independently in haplorhines and strepsirrhines. Anthropoid and lorisid lineages show stasis and decreasing elongation, respectively. Initial increases in calcaneal elongation in primate evolution may be related to either development of hallucal-grasping or a combination of grasping and more specialized leaping behaviors. As has been previously suggested, subsequent increases in calcaneal

Development of replication-deficient adenovirus malaria vaccines.

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Hollingdale, Michael R; Sedegah, Martha; Limbach, Keith

2017-03-01

Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas covered: This review covers current malaria clinical trials using adenoviruses and pre-clinical research. Heterologous prime-boost regimens, including replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are efficacious. However, efficacy appears to be adversely affected by pre-existing anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials including infants in malaria-endemic areas. Key antigens have been identified and are being used alone, in combination, or with protein subunit vaccines. Gorilla adenoviruses carrying malaria antigens are also currently being evaluated in preclinical models. These replacement adenovirus vectors will be successfully used to develop vaccines against malaria, as well as other infectious diseases. Expert commentary: Simplified prime-boost single shot regimens, dry-coated live vector vaccines or silicon microneedle arrays could be developed for malaria or other vaccines. Replacement vectors with similar or superior immunogenicity have rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria as well as other diseases, notably Ebola.

Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication.

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Zou, Wei; Wang, Zekun; Xiong, Min; Chen, Aaron Yun; Xu, Peng; Ganaie, Safder S; Badawi, Yomna; Kleiboeker, Steve; Nishimune, Hiroshi; Ye, Shui Qing; Qiu, Jianming

2018-03-01

Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V. We found that DNA metabolism, DNA replication, DNA repair, DNA damage response, cell cycle, and cell cycle arrest pathways were significantly regulated after B19V infection. Confocal microscopy analyses revealed that most cellular DNA replication proteins were recruited to the centers of viral DNA replication, but not the DNA repair DNA polymerases. Our results suggest that DNA replication polymerase δ and polymerase α are responsible for B19V DNA replication by knocking down its expression in EPCs. We further showed that although RPA32 is essential for B19V DNA replication and the phosphorylated forms of RPA32 colocalized with the replicating viral genomes, RPA32 phosphorylation was not necessary for B19V DNA replication. Thus, this report provides evidence that B19V uses the cellular DNA replication machinery for viral DNA replication. IMPORTANCE Human parvovirus B19 (B19V) infection can cause transient aplastic crisis, persistent viremia, and pure red cell aplasia. In fetuses, B19V infection can result in nonimmune hydrops fetalis and fetal death. These clinical manifestations of B19V infection are a direct outcome of the death of human erythroid progenitors that host B19V replication. B19V infection induces a DNA damage response that is important for cell cycle arrest at late S phase. Here, we analyzed dynamic changes in cellular gene expression and found that DNA metabolic processes are tightly regulated during B19V infection. Although genes involved in cellular DNA replication were downregulated overall, the cellular DNA replication machinery was tightly

Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs.

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Bernard, Marie-Clotilde; Barban, Véronique; Pradezynski, Fabrine; de Montfort, Aymeric; Ryall, Robert; Caillet, Catherine; Londono-Hayes, Patricia

2015-01-01

HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29) has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529) derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige) mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a prophylactic vaccine.

Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs.

Directory of Open Access Journals (Sweden)

Marie-Clotilde Bernard

Full Text Available HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29 has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529 derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a

MOF Suppresses Replication Stress and Contributes to Resolution of Stalled Replication Forks.

Science.gov (United States)

Singh, Dharmendra Kumar; Pandita, Raj K; Singh, Mayank; Chakraborty, Sharmistha; Hambarde, Shashank; Ramnarain, Deepti; Charaka, Vijaya; Ahmed, Kazi Mokim; Hunt, Clayton R; Pandita, Tej K

2018-03-15

The human MOF (hMOF) protein belongs to the MYST family of histone acetyltransferases and plays a critical role in transcription and the DNA damage response. MOF is essential for cell proliferation; however, its role during replication and replicative stress is unknown. Here we demonstrate that cells depleted of MOF and under replicative stress induced by cisplatin, hydroxyurea, or camptothecin have reduced survival, a higher frequency of S-phase-specific chromosome damage, and increased R-loop formation. MOF depletion decreased replication fork speed and, when combined with replicative stress, also increased stalled replication forks as well as new origin firing. MOF interacted with PCNA, a key coordinator of replication and repair machinery at replication forks, and affected its ubiquitination and recruitment to the DNA damage site. Depletion of MOF, therefore, compromised the DNA damage repair response as evidenced by decreased Mre11, RPA70, Rad51, and PCNA focus formation, reduced DNA end resection, and decreased CHK1 phosphorylation in cells after exposure to hydroxyurea or cisplatin. These results support the argument that MOF plays an important role in suppressing replication stress induced by genotoxic agents at several stages during the DNA damage response. Copyright © 2018 American Society for Microbiology.

Homeostasis in primates in hyperacceleration fields

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Fuller, C. A.

1984-01-01

Various homeostatic responses of a nonhuman primate, the squirrel monkey (Saimiri sciureus) to acute changes in the acceleration environment were examined. When these animals were exposed to a hyperdynamic field the body temperature was consistently depressed and the animals showed behavioral indications of increased drowsiness. Further, time of day played a significant role in influencing these responses.

Analysis of dental root apical morphology: a new method for dietary reconstructions in primates.

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Hamon, NoÉmie; Emonet, Edouard-Georges; Chaimanee, Yaowalak; Guy, Franck; Tafforeau, Paul; Jaeger, Jean-Jacques

2012-06-01

The reconstruction of paleo-diets is an important task in the study of fossil primates. Previously, paleo-diet reconstructions were performed using different methods based on extant primate models. In particular, dental microwear or isotopic analyses provided accurate reconstructions for some fossil primates. However, there is sometimes difficult or impossible to apply these methods to fossil material. Therefore, the development of new, independent methods of diet reconstructions is crucial to improve our knowledge of primates paleobiology and paleoecology. This study aims to investigate the correlation between tooth root apical morphology and diet in primates, and its potential for paleo-diet reconstructions. Dental roots are composed of two portions: the eruptive portion with a smooth and regular surface, and the apical penetrative portion which displays an irregular and corrugated surface. Here, the angle formed by these two portions (aPE), and the ratio of penetrative portion over total root length (PPI), are calculated for each mandibular tooth root. A strong correlation between these two variables and the proportion of some food types (fruits, leaves, seeds, animal matter, and vertebrates) in diet is found, allowing the use of tooth root apical morphology as a tool for dietary reconstructions in primates. The method was then applied to the fossil hominoid Khoratpithecus piriyai, from the Late Miocene of Thailand. The paleo-diet deduced from aPE and PPI is dominated by fruits (>50%), associated with animal matter (1-25%). Leaves, vertebrates and most probably seeds were excluded from the diet of Khoratpithecus, which is consistent with previous studies. Copyright © 2012 Wiley Periodicals, Inc.

Conserving social-ecological systems in Indonesia: human-nonhuman primate interconnections in Bali and Sulawesi.

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Riley, Erin P; Fuentes, Agustín

2011-01-01

An important question asked by primatologists and conservationists alike is: what is the relevance of primates and primate conservation for ecosystem conservation? The goal of this article is to contribute to this dialogue by advocating the use of a research perspective that focuses on the dynamics of human-nonhuman primate sympatry and interaction (i.e., ethnoprimatology) in order to better understand complex social-ecological systems and to inform their conservation management. This perspective/approach is based largely on the recognition that human primates are important components of all ecological systems and that niche construction is a fundamental feature of their adaptive success. To demonstrate the relevance of the human-nonhuman primate interface for ecosystem conservation, we provide examples from our research from two islands in the Indonesian archipelago: Bali and Sulawesi. In Bali, humans and long-tail macaques coexist in a system that creates favorable environments for the macaques. This anthropogenic landscape and the economic and ecological relationships between humans and monkeys on Bali provide insight into sustainable systems of human/nonhuman primate coexistence. In Lore Lindu National Park in Central Sulawesi, villagers and Tonkean macaques overlap in their use of both forest and cultivated resources. The finding that the Arenga pinnata palm is extremely important for both villagers and macaques points to a conservation management recommendation that may help protect the overall ecosystem; the cultivation and propagation of mutually important tree species at forest-agricultural ecotone as a means to curb crop raiding and to alleviate farmer's perceived need to clear additional forest.

Research progress of the bitter taste receptor genes in primates.

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Feng, Ping; Luo, Rui-Jian

2018-02-20

Among the five basic tastes (umami, sweet, bitter, salty and sour), the perception of bitterness is believed to protect animals from digesting toxic and harmful substances, thus it is vital for animal survival. The taste of bitterness is triggered by the interaction between bitter substances and bitter taste receptors, which are encoded by Tas2rs. The gene numbers vary largely across species to meet different demands. So far, several ligands of bitter receptors have been identified in primates. They also discovered that the selective pressure of certain bitter taste receptor genes vary across taxa, genes or even different functional regions of the gene. In this review, we summarize the research progress of bitter taste receptor genes in primates by introducing the functional diversity of bitter receptors, the specific interaction between bitter taste receptors and ligands, the relationship between the evolutionary pattern of bitter taste receptors and diets, and the adaptive evolution of bitter taste receptor genes. We aim to provide a reference for further research on bitter receptor genes in primates.

A solution to the worn tooth conundrum in primate functional anatomy.

Science.gov (United States)

Ungar, Peter S; M'Kirera, Francis

2003-04-01

Worn teeth are a bane to paleobiologists interested in the diets of human ancestors and other fossil primates. Although worn teeth dominate fossil assemblages, their shapes are usually not used to reconstruct the diets of extinct species. The problem is that traditional studies of primate dental functional anatomy have focused on unworn morphology. This has limited most functional analyses to only a few well-represented fossil species. This paper introduces a method to characterize and compare worn occlusal morphology in primates using laser scanning and geographic information systems technologies. A study of variably worn chimpanzee and gorilla molars indicates that differences between these species in tooth shape remain consistent at given stages of wear. Although cusp slope decreases with wear in both taxa, angularity values remain unchanged. These results indicate that African ape teeth wear in a manner that keeps them mechanically efficient for fracturing specific foods. Studies of changes in tooth shape with wear add a new dimension to dental functional anatomy, and offer a more complete picture of dental-dietary adaptations. Also, given how rare unworn teeth are in the fossil record, the ability to include worn specimens in analyses opens the door to reconstructing the diets of many more extinct primate groups, allowing us to better understand the adaptive radiation of our order.

Database Replication

CERN Document Server

Kemme, Bettina

2010-01-01

Database replication is widely used for fault-tolerance, scalability and performance. The failure of one database replica does not stop the system from working as available replicas can take over the tasks of the failed replica. Scalability can be achieved by distributing the load across all replicas, and adding new replicas should the load increase. Finally, database replication can provide fast local access, even if clients are geographically distributed clients, if data copies are located close to clients. Despite its advantages, replication is not a straightforward technique to apply, and

Sources of variation in hair cortisol in wild and captive non-human primates.

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Fourie, Nicolaas H; Brown, Janine L; Jolly, Clifford J; Phillips-Conroy, Jane E; Rogers, Jeffrey; Bernstein, Robin M

2016-04-01

Hair cortisol analysis is a potentially powerful tool for evaluating adrenal function and chronic stress. However, the technique has only recently been applied widely to studies of wildlife, including primates, and there are numerous practical and technical factors that should be considered to ensure good quality data and the validity of results and conclusions. Here we report on various intrinsic and extrinsic sources of variation in hair cortisol measurements in wild and captive primates. Hair samples from both wild and captive primates revealed that age and sex can affect hair cortisol concentrations; these effects need to be controlled for when making comparisons between individual animals or populations. Hair growth rates also showed considerable inter-specific variation among a number of primate species. We describe technical limitations of hair analyses and variation in cortisol concentrations as a function of asynchronous hair growth, anatomical site of collection, and the amount and numbers of hair/s used for cortisol extraction. We discuss these sources of variation and their implications for proper study design and interpretation of results. Published by Elsevier GmbH.

Visual cortical areas of the mouse: comparison of parcellation and network structure with primates

Directory of Open Access Journals (Sweden)

Marie-Eve eLaramée

2015-01-01

Full Text Available Brains have evolved to optimize sensory processing. In primates, complex cognitive tasks must be executed and evolution led to the development of large brains with many cortical areas. Rodents do not accomplish cognitive tasks of the same level of complexity as primates and remain with small brains both in relative and absolute terms. But is a small brain necessarily a simple brain? In this review, several aspects of the visual cortical networks have been compared between rodents and primates. The visual system has been used as a model to evaluate the level of complexity of the cortical circuits at the anatomical and functional levels. The evolutionary constraints are first presented in order to appreciate the rules for the development of the brain and its underlying circuits. The organization of sensory pathways, with their parallel and cross-modal circuits, is also examined. Other features of brain networks, often considered as imposing constraints on the development of underlying circuitry, are also discussed and their effect on the complexity of the mouse and primate brain are inspected. In this review, we discuss the common features of cortical circuits in mice and primates and see how these can be useful in understanding visual processing in these animals.

Visual cortical areas of the mouse: comparison of parcellation and network structure with primates

Science.gov (United States)

Laramée, Marie-Eve; Boire, Denis

2015-01-01

Brains have evolved to optimize sensory processing. In primates, complex cognitive tasks must be executed and evolution led to the development of large brains with many cortical areas. Rodents do not accomplish cognitive tasks of the same level of complexity as primates and remain with small brains both in relative and absolute terms. But is a small brain necessarily a simple brain? In this review, several aspects of the visual cortical networks have been compared between rodents and primates. The visual system has been used as a model to evaluate the level of complexity of the cortical circuits at the anatomical and functional levels. The evolutionary constraints are first presented in order to appreciate the rules for the development of the brain and its underlying circuits. The organization of sensory pathways, with their parallel and cross-modal circuits, is also examined. Other features of brain networks, often considered as imposing constraints on the development of underlying circuitry, are also discussed and their effect on the complexity of the mouse and primate brain are inspected. In this review, we discuss the common features of cortical circuits in mice and primates and see how these can be useful in understanding visual processing in these animals. PMID:25620914

Visual cortical areas of the mouse: comparison of parcellation and network structure with primates.

Science.gov (United States)

Laramée, Marie-Eve; Boire, Denis

2014-01-01

Brains have evolved to optimize sensory processing. In primates, complex cognitive tasks must be executed and evolution led to the development of large brains with many cortical areas. Rodents do not accomplish cognitive tasks of the same level of complexity as primates and remain with small brains both in relative and absolute terms. But is a small brain necessarily a simple brain? In this review, several aspects of the visual cortical networks have been compared between rodents and primates. The visual system has been used as a model to evaluate the level of complexity of the cortical circuits at the anatomical and functional levels. The evolutionary constraints are first presented in order to appreciate the rules for the development of the brain and its underlying circuits. The organization of sensory pathways, with their parallel and cross-modal circuits, is also examined. Other features of brain networks, often considered as imposing constraints on the development of underlying circuitry, are also discussed and their effect on the complexity of the mouse and primate brain are inspected. In this review, we discuss the common features of cortical circuits in mice and primates and see how these can be useful in understanding visual processing in these animals.

Clinical Laboratory Values as Early Indicators of Ebola Virus Infection in Nonhuman Primates.

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Reisler, Ronald B; Yu, Chenggang; Donofrio, Michael J; Warren, Travis K; Wells, Jay B; Stuthman, Kelly S; Garza, Nicole L; Vantongeren, Sean A; Donnelly, Ginger C; Kane, Christopher D; Kortepeter, Mark G; Bavari, Sina; Cardile, Anthony P

2017-08-01

The Ebola virus (EBOV) outbreak in West Africa during 2013-2016 demonstrated the need to improve Ebola virus disease (EVD) diagnostics and standards of care. This retrospective study compared laboratory values and clinical features of 3 nonhuman primate models of lethal EVD to assess associations with improved survival time. In addition, the study identified laboratory values useful as predictors of survival, surrogates for EBOV viral loads, and triggers for initiation of therapeutic interventions in these nonhuman primate models. Furthermore, the data support that, in nonhuman primates, the Makona strain of EBOV may be less virulent than the Kikwit strain of EBOV. The applicability of these findings as potential diagnostic and management tools for EVD in humans warrants further investigation.

Anatomical Network Analysis Shows Decoupling of Modular Lability and Complexity in the Evolution of the Primate Skull

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Esteve-Altava, Borja; Boughner, Julia C.; Diogo, Rui; Villmoare, Brian A.; Rasskin-Gutman, Diego

2015-01-01

Modularity and complexity go hand in hand in the evolution of the skull of primates. Because analyses of these two parameters often use different approaches, we do not know yet how modularity evolves within, or as a consequence of, an also-evolving complex organization. Here we use a novel network theory-based approach (Anatomical Network Analysis) to assess how the organization of skull bones constrains the co-evolution of modularity and complexity among primates. We used the pattern of bone contacts modeled as networks to identify connectivity modules and quantify morphological complexity. We analyzed whether modularity and complexity evolved coordinately in the skull of primates. Specifically, we tested Herbert Simon’s general theory of near-decomposability, which states that modularity promotes the evolution of complexity. We found that the skulls of extant primates divide into one conserved cranial module and up to three labile facial modules, whose composition varies among primates. Despite changes in modularity, statistical analyses reject a positive feedback between modularity and complexity. Our results suggest a decoupling of complexity and modularity that translates to varying levels of constraint on the morphological evolvability of the primate skull. This study has methodological and conceptual implications for grasping the constraints that underlie the developmental and functional integration of the skull of humans and other primates. PMID:25992690

Nonhuman primate positron emission tomography neuroimaging in drug abuse research.

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Howell, Leonard Lee; Murnane, Kevin Sean

2011-05-01

Positron emission tomography (PET) neuroimaging in nonhuman primates has led to significant advances in our current understanding of the neurobiology and treatment of stimulant addiction in humans. PET neuroimaging has defined the in vivo biodistribution and pharmacokinetics of abused drugs and related these findings to the time course of behavioral effects associated with their addictive properties. With novel radiotracers and enhanced resolution, PET neuroimaging techniques have also characterized in vivo drug interactions with specific protein targets in the brain, including neurotransmitter receptors and transporters. In vivo determinations of cerebral blood flow and metabolism have localized brain circuits implicated in the effects of abused drugs and drug-associated stimuli. Moreover, determinations of the predisposing factors to chronic drug use and long-term neurobiological consequences of chronic drug use, such as potential neurotoxicity, have led to novel insights regarding the pathology and treatment of drug addiction. However, similar approaches clearly need to be extended to drug classes other than stimulants. Although dopaminergic systems have been extensively studied, other neurotransmitter systems known to play a critical role in the pharmacological effects of abused drugs have been largely ignored in nonhuman primate PET neuroimaging. Finally, the study of brain activation with PET neuroimaging has been replaced in humans mostly by functional magnetic resonance imaging (fMRI). There has been some success in implementing pharmacological fMRI in awake nonhuman primates. Nevertheless, the unique versatility of PET imaging will continue to complement the systems-level strengths of fMRI, especially in the context of nonhuman primate drug abuse research.

X-irradiation affects all DNA replication intermediates when inhibiting replication initiation

International Nuclear Information System (INIS)

Loenn, U.; Karolinska Hospital, Stockholm

1982-01-01

When a human melanoma line was irradiated with 10 Gy, there was, after 30 to 60 min, a gradual reduction in the DNA replication rate. Ten to twelve hours after the irradiation, the DNA replication had returned to near normal rate. The results showed tht low dose-rate X-irradiation inhibits preferentially the formation of small DNA replication intermediates. There is no difference between the inhibition of these replication intermediates formed only in the irradiated cells and those formed also in untreated cells. (U.K.)

Chromatin Structure and Replication Origins: Determinants Of Chromosome Replication And Nuclear Organization

Science.gov (United States)

Smith, Owen K.; Aladjem, Mirit I.

2014-01-01

The DNA replication program is, in part, determined by the epigenetic landscape that governs local chromosome architecture and directs chromosome duplication. Replication must coordinate with other biochemical processes occurring concomitantly on chromatin, such as transcription and remodeling, to insure accurate duplication of both genetic and epigenetic features and to preserve genomic stability. The importance of genome architecture and chromatin looping in coordinating cellular processes on chromatin is illustrated by two recent sets of discoveries. First, chromatin-associated proteins that are not part of the core replication machinery were shown to affect the timing of DNA replication. These chromatin-associated proteins could be working in concert, or perhaps in competition, with the transcriptional machinery and with chromatin modifiers to determine the spatial and temporal organization of replication initiation events. Second, epigenetic interactions are mediated by DNA sequences that determine chromosomal replication. In this review we summarize recent findings and current models linking spatial and temporal regulation of the replication program with epigenetic signaling. We discuss these issues in the context of the genome’s three-dimensional structure with an emphasis on events occurring during the initiation of DNA replication. PMID:24905010

Prelife catalysts and replicators

OpenAIRE

Ohtsuki, Hisashi; Nowak, Martin A.

2009-01-01

Life is based on replication and evolution. But replication cannot be taken for granted. We must ask what there was prior to replication and evolution. How does evolution begin? We have proposed prelife as a generative system that produces information and diversity in the absence of replication. We model prelife as a binary soup of active monomers that form random polymers. ‘Prevolutionary’ dynamics can have mutation and selection prior to replication. Some sequences might have catalytic acti...

Curing color blindness--mice and nonhuman primates.

Science.gov (United States)

Neitz, Maureen; Neitz, Jay

2014-08-21

It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates, red-green color vision in mice is poor, indicating large differences between mice and monkeys in their ability to take advantage of the new input. These results have implications for understanding the limits and opportunities for using gene therapy to treat vision disorders caused by defects in cone function. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Interspecific perspective on mechanical and nonmechanical models of primate circumorbital morphology.

Science.gov (United States)

Ravosa, M J

1991-11-01

Linear dimensions and angular orientations of the browridge, postorbital bar, and postorbital septum were obtained from a representative series of primates and compared with variables associated with several nonmechanical and biomechanical/mechanical models put forward to explain the form and function of the circumorbital region. Analyses of the results indicate that face size is the primary determinant of variation in primate circumorbital morphology. Anteroposterior browridge thickness is correlated with neural-orbital disjunction among anthropoid primates, but not among prosimians. This difference appears related to differences in the construction of the upper face and anterior cranial fossa between prosimians and anthropoids. Little support is demonstrated for the anterior dental loading model of browridge development. Mediolateral postorbital bar width and (to a lesser degree) browridge height are correlated with neurofacial torsion during mastication and variation in masticatory muscle size. These analyses further suggest that since circumorbital structures (especially the browridges) are located the farthest away from the chewing apparatus, they are least affected by masticatory stresses.

Data from Investigating Variation in Replicability: A “Many Labs” Replication Project

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Richard A. Klein

2014-04-01

Full Text Available This dataset is from the Many Labs Replication Project in which 13 effects were replicated across 36 samples and over 6,000 participants. Data from the replications are included, along with demographic variables about the participants and contextual information about the environment in which the replication was conducted. Data were collected in-lab and online through a standardized procedure administered via an online link. The dataset is stored on the Open Science Framework website. These data could be used to further investigate the results of the included 13 effects or to study replication and generalizability more broadly.

Characterization of interleukin-8 receptors in non-human primates

Energy Technology Data Exchange (ETDEWEB)

Alvarez, V.; Coto, E.; Gonzalez-Roces, S.; Lopez-Larrea, C. [Hospital Central de Asturias, Oviedo (Spain)] [and others

1996-09-01

Interleukin-8 is a chemokine with a potent neutrophil chemoatractant activity. In humans, two different cDNAs encoding human IL8 receptors designated IL8RA and IL8RB have been cloned. IL8RA binds IL8, while IL8RB binds IL8 as well as other {alpha}-chemokines. Both human IL8Rs are encoded by two genes physically linked on chromosome 2. The IL8RA and IL8RB genes have open reading frames (ORF) lacking introns. By direct sequencing of the polymerase chain reaction products, we sequenced the IL8R genes of cell lines from four non-human primates: chimpanzee, gorilla, orangutan, and macaca. The IL8RB encodes an ORF in the four non-human primates, showing 95%-99% similarity to the human IL8RB sequence. The IL8RA homologue in gorilla and chimpanzee consisted of two ORF 98%-99% identical to the human sequence. The macaca and orangutan IL8RA homologues are pseudogenes: a 2 base pair insertion generated a sequence with several stop codons. In addition, we describe the physical linkage of these genes in the four non-human primates and discuss the evolutionary implications of these findings. 25 refs., 5 figs., 3 tabs.

Adaptive cultural transmission biases in children and nonhuman primates.

Science.gov (United States)

Price, Elizabeth E; Wood, Lara A; Whiten, Andrew

2017-08-01

Comparative and evolutionary developmental analyses seek to discover the similarities and differences between humans and non-human species that might illuminate both the evolutionary foundations of our nature that we share with other animals, and the distinctive characteristics that make human development unique. As our closest animal relatives, with whom we last shared common ancestry, non-human primates have been particularly important in this endeavour. Such studies have focused on social learning, traditions, and culture, and have discovered much about the 'how' of social learning, concerned with key underlying processes such as imitation and emulation. One of the core discoveries is that the adaptive adjustment of social learning options to different contexts is not unique to human, therefore multiple new strands of research have begun to focus on more subtle questions about when, from whom, and why such learning occurs. Here we review illustrative studies on both human infants and young children and on non-human primates to identify the similarities shared more broadly across the primate order, and the apparent specialisms that distinguish human development. Adaptive biases in social learning discussed include those modulated by task comprehension, experience, conformity to majorities, and the age, skill, proficiency and familiarity of potential alternative cultural models. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Virus-host interaction in feline immunodeficiency virus (FIV) infection.

Science.gov (United States)

Taniwaki, Sueli Akemi; Figueiredo, Andreza Soriano; Araujo, João Pessoa

2013-12-01

Feline immunodeficiency virus (FIV) infection has been the focus of several studies because this virus exhibits genetic and pathogenic characteristics that are similar to those of the human immunodeficiency virus (HIV). FIV causes acquired immunodeficiency syndrome (AIDS) in cats, nevertheless, a large fraction of infected cats remain asymptomatic throughout life despite of persistent chronic infection. This slow disease progression may be due to the presence of factors that are involved in the natural resistance to infection and the immune response that is mounted by the animals, as well as due to the adaptation of the virus to the host. Therefore, the study of virus-host interaction is essential to the understanding of the different patterns of disease course and the virus persistence in the host, and to help with the development of effective vaccines and perhaps the cure of FIV and HIV infections. Copyright © 2013 Elsevier Ltd. All rights reserved.

Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection

Energy Technology Data Exchange (ETDEWEB)

Subramanian, T.; Zhao, Ling-jun; Chinnadurai, G., E-mail: chinnag@slu.edu

2013-09-01

Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP–E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP–E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. - Highlights: • Adenovirus E1A C-terminal region suppresses E1A/Ras co-transformation. • This E1A region binds with FOXK, DYRK1/HAN11 and CtBP cellular protein complexes. • We found that E1A–CtBP interaction suppresses immortalization and transformation. • The interaction enhances viral replication in human cells.

Energetics of feeding, social behavior, and life history in non-human primates.

Science.gov (United States)

Emery Thompson, Melissa

2017-05-01

Energy is a variable of key importance to a wide range of research in primate behavioral ecology, life history, and conservation. However, obtaining detailed data on variation in energetic condition, and its biological consequences, has been a considerable challenge. In the past 20years, tremendous strides have been made towards non-invasive methods for monitoring the physiology of animals in their natural environment. These methods provide detailed, individualized data about energetic condition, as well as energy allocations to growth, reproduction, and somatic health. In doing so, they add much-needed resolution by which to move beyond correlative studies to research programs that can discriminate causes from effects and disaggregate multiple correlated features of the social and physical environment. In this review, I describe the conceptual and methodological approaches for studying primate energetics. I then discuss the core questions about primate feeding ecology, social behavior, and life history that can benefit from physiological studies, highlighting the ways in which recent research has done so. Among these are studies that test, and often refute, common assumptions about how feeding ecology shapes primate biology, and those that reveal proximate associations between energetics and reproductive strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

Diminished internalization and action of 1,25-dihydroxyvitamin D3 in dermal fibroblasts cultured from New World primates

International Nuclear Information System (INIS)

Adams, J.S.; Gacad, M.A.; Baker, A.J.; Kheun, G.; Rude, R.K.

1985-01-01

We investigated the occurrence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-resistant osteomalacia in the New World primate colony of Saguinus imperator at the Los Angeles Zoo. The mean serum concentration of 1,25-(OH)2D3 was elevated 5-fold in the New World primates compared to that in their Old World counterparts. The specific internalization of 0.6 nM [ 3 H]1,25-(OH)2D3 by cultured dermal fibroblasts from New World primates was reduced 75% compared to that by cells from Old World primates or man. The decrease in hormone uptake resulted from a decrease in the number of high affinity intracellular binding sites for 1,25-(OH)2D3 and apparently caused a 90-95% reduction in 1,25-(OH)2D3-induced 25-hydroxyvitamin-D3-24-hydroxylase activity. There was no alteration in the capacity or avidity of New World primate serum for 1,25-(OH)2D3 compared to that of serum from Old World primates. These data suggest that the occurrence of vitamin D-resistant osteomalacia in New World primates is the result of decreased high affinity, receptor-mediated uptake of 1,25-(OH)2D3 by the target cell

Crystal Structure of the Full-Length Feline Immunodeficiency Virus Capsid Protein Shows an N-Terminal β-Hairpin in the Absence of N-Terminal Proline

Directory of Open Access Journals (Sweden)

Christelle Folio

2017-11-01

Full Text Available Feline immunodeficiency virus (FIV is a member of the Retroviridae family. It is the causative agent of an acquired immunodeficiency syndrome (AIDS in cats and wild felines. Its capsid protein (CA drives the assembly of the viral particle, which is a critical step in the viral replication cycle. Here, the first atomic structure of full-length FIV CA to 1.67 Å resolution is determined. The crystallized protein exhibits an original tetrameric assembly, composed of dimers which are stabilized by an intermolecular disulfide bridge induced by the crystallogenesis conditions. The FIV CA displays a standard α-helical CA topology with two domains, separated by a linker shorter than other retroviral CAs. The β-hairpin motif at its amino terminal end, which interacts with nucleotides in HIV-1, is unusually long in FIV CA. Interestingly, this functional β-motif is formed in this construct in the absence of the conserved N-terminal proline. The FIV CA exhibits a cis Arg–Pro bond in the CypA-binding loop, which is absent in known structures of lentiviral CAs. This structure represents the first tri-dimensional structure of a functional, full-length FIV CA.

Socioeconomic contexts of primate conservation: population, poverty, global economic demands, and sustainable land use.

Science.gov (United States)

Estrada, Alejandro

2013-01-01

Recent assessments by the International Union for Conservation of Nature (IUCN) indicate the existence of about 612 recognized primate species and subspecies (IUCN RedList, 2012), but close to 50% of these taxa are at risk of extinction as a result of human action. In this article, I call attention to underlying regional and global socioeconomic contexts of primate conservation. Using information from FAO and UN databases and other sources, I examine, for the Neotropics, sub-Saharan Africa, and Southeast Asia, trends in forest loss and human demographics and social condition, discuss the impact of global market pressures upon primate habitats, and examine land-use patterns that may favor primate conservation. Between 1990 and 2010, an estimated 149 million ha of forest were lost in the three regions and additional losses are expected in the future. Global human population will increase from 7 billion in 2012 to 9 billion in 2050. Currently, 2 billion people live in the three primate range regions under high levels of poverty. Large-scale deforestation is related to global market demands, especially from developed and developing nations, for food (e.g., cattle), domestic animal feed (e.g., soybeans), biofuel-based crops (e.g., oil palm), and industrial round wood. The growth of protected areas in the three regions has been steady for several decades, but it is not enough to ensure long-term conservation of many primate taxa. Other conservations tools involving sustainable land use and biodiversity conservation corridors are required at the landscape level. The above assessment can easily be applied at the local level by primatologists, giving more precision to conservation initiatives. © 2012 Wiley Periodicals, Inc.

Cranial vault thickness in primates: Homo erectus does not have uniquely thick vault bones.

Science.gov (United States)

Copes, Lynn E; Kimbel, William H

2016-01-01

Extremely thick cranial vaults have been noted as a diagnostic characteristic of Homo erectus since the first fossil of the species was identified, but relatively little work has been done on elucidating its etiology or variation across fossils, living humans, or extant non-human primates. Cranial vault thickness (CVT) is not a monolithic trait, and the responsiveness of its layers to environmental stimuli is unknown. We obtained measurements of cranial vault thickness in fossil hominins from the literature and supplemented those data with additional measurements taken on African fossil specimens. Total CVT and the thickness of the cortical and diploë layers individually were compared to measures of CVT in extant species measured from more than 500 CT scans of human and non-human primates. Frontal and parietal CVT in fossil primates was compared to a regression of CVT on cranial capacity calculated for extant species. Even after controlling for cranial capacity, African and Asian H. erectus do not have uniquely high frontal or parietal thickness residuals, either among hominins or extant primates. Extant primates with residual CVT thickness similar to or exceeding H. erectus (depending on the sex and bone analyzed) include Nycticebus coucang, Perodicticus potto, Alouatta caraya, Lophocebus albigena, Galago alleni, Mandrillus sphinx, and Propithecus diadema. However, the especially thick vaults of extant non-human primates that overlap with H. erectus values are composed primarily of cortical bone, while H. erectus and other hominins have diploë-dominated vault bones. Thus, the combination of thick vaults comprised of a thickened diploë layer may be a reliable autapomorphy for members of the genus Homo. Copyright © 2015 Elsevier Ltd. All rights reserved.

PRIMARY IMMUNODEFICIENCY: STATUS OF A PROBLEM TODAY. RUSSIAN NETWORK OF JMF-CENTERS

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E. A. Latysheva

2013-01-01

Full Text Available The problems of primary immunodeficiency in Russia and the ways of solving of them are discussed in the article. Primary immunodeficiency is a group of rare diseases, so awareness of this pathology in the medical community and among patients is very low. This leads to late diagnosis and inadequate treatment of patients with such conditions. The result of the late beginning of treatment is early development of disability, and the high mortality rate of patients, as well as the high costs of the treatment of complications of primary immunodeficiency and sick-leave certificates for the government. Today in time and adequate therapy allows patients not only to reach adulthood without signs of disability, and to lead an active way of life, but to have healthy children. Given the high cost of therapy in many countries, the issue of providing patients with life-saving drugs remains unresolved. The global practice is to involve social organizations and funds. One of the foundations supporting educational programs, development of laboratories and research in the field of primary immunodeficiency is the Foundation of the Jeffrey Modell. A network of centres for primary immunodeficiency supported by the Jeffrey Modell Foundation (JMF-centers has started its functioning over the territory of the Russian Federation since 2011 in order to improve diagnostics and treatment of patients with primary immunodeficiency. A brief description of activity of these centers is presented in the article.

Interleukin-9 receptor α chain mRNA formation in CD8+ T cells producing anti-human immunodeficiency virus type 1 substance(s)

International Nuclear Information System (INIS)

Hossain, M.M.; Tsuchie, H.; Detorio, M.A.; Shirono, H.; Hara, C.; Nishimoto, A.; Saji, A.; Koga, J.; Takata, N.; Maniar, J.K.; Saple, D.G.; Taniguchi, K.; Kageyama, S.; Ichimura, H.; Kurimura, T.

1998-01-01

A search for gene(s) associated with anti-human immunodeficiency virus type 1 (HIV-l) activity of CD8 + T cells was attempted using molecular cloning and the relation between the anti-HIV activity of CD8 + T cells and the interleukin-9 receptor a chain (IL-9R-α) mRNA expression from the cDNA clones obtained was examined. The anti-HIV-l activity of CD8 + T cell culture supernatants was assessed by measuring the level of HIV-l replication in a CD4 + T cell line transfected with an infectious HIV-l DNA clone. IL-9R-a mRNA was assayed by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 5 cases showing high level of anti-HIV-l activity (more than 80% suppression of HIV-l replication), the mRNA was detected in 4 cases. Of 10 cases showing low level of anti-HIV-l activity (less than 80% suppression of HIV-l replication), the mRNA was detected in one case. Soluble recombinant human IL-9 receptor (rhIL-9sR) did not suppress HIV-l replication at a concentration of 1 μg/ml. These data suggest that the IL-9R-a mRNA formation in CD8 + T cells may correlate with and play some role in the anti-HIV-l activity of CD8+ T cells from HIV-l-infected individuals. Key words: CD8+ T cells; anti-HIV-l activity; cytokines; interleukin-9 receptor (authors)

Acquired immunodeficiency syndrome/human immunodeficiency virus knowledge, attitudes, and practices, and use of healthcare services among rural migrants: a cross-sectional study in China

OpenAIRE

Wang, Ying; Cochran, Christopher; Xu, Peng; Shen, Jay J; Zeng, Gang; Xu, Yanjun; Sun, Mei; Li, Chengyue; Li, Xiaohong; Chang, Fengshui; Lu, Jun; Hao, Mo; Lu, Fan

2014-01-01

Background Today’s rapid growth of migrant populations has been a major contributor to the human immunodeficiency virus (HIV) epidemic. However, relatively few studies have focused on HIV/acquired immunodeficiency syndrome (AIDS)-related knowledge, attitudes, and practice among rural-to-urban migrants in China. This cross-sectional study was to assess HIV/AIDS-related knowledge and perceptions, including knowledge about reducing high-risk sex. Methods Two-phase stratified cluster sampling was...

Stability of the Gorilla Microbiome Despite SIV Infection

OpenAIRE

Moeller, Andrew H.; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H.; Ochman, Howard

2015-01-01

Simian Immunodeficiency Viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in fecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. He...

[Interdisciplinary AWMF guideline for the diagnostics of primary immunodeficiency].

Science.gov (United States)

Farmand, S; Baumann, U; von Bernuth, H; Borte, M; Foerster-Waldl, E; Franke, K; Habermehl, P; Kapaun, P; Klock, G; Liese, J; Marks, R; Müller, R; Nebe, T; Niehues, T; Schuster, V; Warnatz, K; Witte, T; Ehl, S; Schulze, I

2011-11-01

Primary immunodeficiencies are potentially life-threatening diseases. Over the last years, the clinical phenotype and the molecular basis of an increasing number of immunological defects have been characterized. However, in daily practice primary immunodeficiencies are still often diagnosed too late. Considering that an early diagnosis may reduce morbidity and mortality of affected patients, an interdisciplinary guideline for the diagnosis of primary immunodeficiencies was developed on behalf of the Arbeitsgemeinschaft Pädiatrische Immunologie (API) and the Deutsche Gesellschaft für Immunologie (DGfI). The guideline is based on expert opinion and on knowledge from other guidelines and recommendations from Germany and other countries, supplemented by data from studies that support the postulated key messages (level of evidence III). With the contribution of 20 representatives, belonging to 14 different medical societies and associations, a consensus-based guideline with a representative group of developers and a structured consensus process was created (S2k). Under the moderation of a representative of the Association of the Scientific Medical Societies in Germany (AWMF) the nominal group process took place in April 2011. The postulated key messages were discussed and voted on following a structured consensus procedure. In particular, modified warning signs for primary immunodeficiencies were formulated and immunological emergency situations were defined. © Georg Thieme Verlag KG Stuttgart · New York.

Viral RNA annealing activities of human immunodeficiency virus type 1 nucleocapsid protein require only peptide domains outside the zinc fingers.

Science.gov (United States)

De Rocquigny, H; Gabus, C; Vincent, A; Fournié-Zaluski, M C; Roques, B; Darlix, J L

1992-07-15

The nucleocapsid (NC) of human immunodeficiency virus type 1 consists of a large number of NC protein molecules, probably wrapping the dimeric RNA genome within the virion inner core. NC protein is a gag-encoded product that contains two zinc fingers flanked by basic residues. In human immunodeficiency virus type 1 virions, NCp15 is ultimately processed into NCp7 and p6 proteins. During virion assembly the retroviral NC protein is necessary for core formation and genomic RNA encapsidation, which are essential for virus infectivity. In vitro NCp15 activates viral RNA dimerization, a process most probably linked in vivo to genomic RNA packaging, and replication primer tRNA(Lys,3) annealing to the initiation site of reverse transcription. To characterize the domains of human immunodeficiency virus type 1 NC protein necessary for its various functions, the 72-amino acid NCp7 and several derived peptides were synthesized in a pure form. We show here that synthetic NCp7 with or without the two zinc fingers has the RNA annealing activities of NCp15. Further deletions of the N-terminal 12 and C-terminal 8 amino acids, leading to a 27-residue peptide lacking the finger domains, have little or no effect on NC protein activity in vitro. However deletion of short sequences containing basic residues flanking the first finger leads to a complete loss of NC protein activity. It is proposed that the basic residues and the zinc fingers cooperate to select and package the genomic RNA in vivo. Inhibition of the viral RNA binding and annealing activities associated with the basic residues flanking the first zinc finger of NC protein could therefore be used as a model for the design of antiviral agents.

Functions of Ubiquitin and SUMO in DNA Replication and Replication Stress

Science.gov (United States)

García-Rodríguez, Néstor; Wong, Ronald P.; Ulrich, Helle D.

2016-01-01

Complete and faithful duplication of its entire genetic material is one of the essential prerequisites for a proliferating cell to maintain genome stability. Yet, during replication DNA is particularly vulnerable to insults. On the one hand, lesions in replicating DNA frequently cause a stalling of the replication machinery, as most DNA polymerases cannot cope with defective templates. This situation is aggravated by the fact that strand separation in preparation for DNA synthesis prevents common repair mechanisms relying on strand complementarity, such as base and nucleotide excision repair, from working properly. On the other hand, the replication process itself subjects the DNA to a series of hazardous transformations, ranging from the exposure of single-stranded DNA to topological contortions and the generation of nicks and fragments, which all bear the risk of inducing genomic instability. Dealing with these problems requires rapid and flexible responses, for which posttranslational protein modifications that act independently of protein synthesis are particularly well suited. Hence, it is not surprising that members of the ubiquitin family, particularly ubiquitin itself and SUMO, feature prominently in controlling many of the defensive and restorative measures involved in the protection of DNA during replication. In this review we will discuss the contributions of ubiquitin and SUMO to genome maintenance specifically as they relate to DNA replication. We will consider cases where the modifiers act during regular, i.e., unperturbed stages of replication, such as initiation, fork progression, and termination, but also give an account of their functions in dealing with lesions, replication stalling and fork collapse. PMID:27242895

Serodiagnosis of Helicobacter pylori infection in patients with human immunodeficiency virus infection

DEFF Research Database (Denmark)

Nielsen, H; Andersen, L P

1995-01-01

In contrast to the established role of Helicobacter pylori gastritis in gastritis and duodenal ulcer in general, conflicting results have been reported in patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome. The seroprevalence during early HIV...

Antiviral treatment for chronic hepatitis C in patients with human immunodeficiency virus

DEFF Research Database (Denmark)

Iorio, Alfonso; Marchesini, Emanuela; Awad, Tahany

2010-01-01

Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV).......Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV)....

Evaluating the Genetics of Common Variable Immunodeficiency: Monogenetic Model and Beyond

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Guillem de Valles-Ibáñez

2018-05-01

Full Text Available Common variable immunodeficiency (CVID is the most frequent symptomatic primary immunodeficiency characterized by recurrent infections, hypogammaglobulinemia and poor response to vaccines. Its diagnosis is made based on clinical and immunological criteria, after exclusion of other diseases that can cause similar phenotypes. Currently, less than 20% of cases of CVID have a known underlying genetic cause. We have analyzed whole-exome sequencing and copy number variants data of 36 children and adolescents diagnosed with CVID and healthy relatives to estimate the proportion of monogenic cases. We have replicated an association of CVID to p.C104R in TNFRSF13B and reported the second case of homozygous patient to date. Our results also identify five causative genetic variants in LRBA, CTLA4, NFKB1, and PIK3R1, as well as other very likely causative variants in PRKCD, MAPK8, or DOCK8 among others. We experimentally validate the effect of the LRBA stop-gain mutation which abolishes protein production and downregulates the expression of CTLA4, and of the frameshift indel in CTLA4 producing expression downregulation of the protein. Our results indicate a monogenic origin of at least 15–24% of the CVID cases included in the study. The proportion of monogenic patients seems to be lower in CVID than in other PID that have also been analyzed by whole exome or targeted gene panels sequencing. Regardless of the exact proportion of CVID monogenic cases, other genetic models have to be considered for CVID. We propose that because of its prevalence and other features as intermediate penetrancies and phenotypic variation within families, CVID could fit with other more complex genetic scenarios. In particular, in this work, we explore the possibility of CVID being originated by an oligogenic model with the presence of heterozygous mutations in interacting proteins or by the accumulation of detrimental variants in particular immunological pathways, as well as

NACSA Charter School Replication Guide: The Spectrum of Replication Options. Authorizing Matters. Replication Brief 1

Science.gov (United States)

O'Neill, Paul

2010-01-01