WorldWideScience

Sample records for human retrovirus infection

  1. Linking human beta retrovirus infection with primary biliary cirrhosis.

    Science.gov (United States)

    Mason, A L; Zhang, G

    2010-01-01

    Several environmental agents have been linked with primary biliary cirrhosis (PBC) that include bacteria, xenobiotics and viruses. A human beta retrovirus (HBRV) related to mouse mammary tumor virus has been cloned and characterized from patients with PBC. This agent can be detected in the majority of patients' perihepatic lymph nodes by immunochemistry and RT-PCR. The HBRV has recently been isolated in culture and integration sites have been identified in the genome of patients to provide convincing evidence of beta retrovirus infection in patients. Three lines of evidence support a role for the virus in PBC. First, the beta retrovirus is linked with aberrant expression of mitochondrial protein(s) on the biliary epithelium cell (BEC) surface, a disease specific phenotype. Second, the related agent, mouse mammary tumor virus has been linked with autoimmune biliary disease in the NOD.c3c4 mouse model for PBC. In this mouse model, the virus is localized to diseased biliary epithelium that also display aberrant expression of the mitochondrial autoantigens. In translational studies, both patients with PBC and NOD.c3c4 mice demonstrate significant improvement in biliary disease with combination antiviral therapy. An overview of the biological relevance of the beta retrovirus infection in PBC will be discussed in this review. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  2. Characterization of resistance to rhabdovirus and retrovirus infection in a human myeloid cell line.

    Science.gov (United States)

    Boso, Guney; Somia, Nikunj V

    2015-01-01

    Viruses interact with various permissive and restrictive factors in host cells throughout their replication cycle. Cell lines that are non-permissive to viral infection have been particularly useful in discovering host cell proteins involved in viral life cycles. Here we describe the characterization of a human myeloid leukemia cell line, KG-1, that is resistant to infection by retroviruses and a Rhabdovirus. We show that KG-1 cells are resistant to infection by Vesicular Stomatits Virus as well as VSV Glycoprotein (VSVG) pseudotyped retroviruses due to a defect in binding. Moreover our results indicate that entry by xenotropic retroviral envelope glycoprotein RD114 is impaired in KG-1 cells. Finally we characterize a post- entry block in the early phase of the retroviral life cycle in KG-1 cells that renders the cell line refractory to infection. This cell line will have utility in discovering proteins involved in infection by VSV and HIV-1.

  3. Infection with human retroviruses other than HIV-1: HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4.

    Science.gov (United States)

    Nicolás, David; Ambrosioni, Juan; Paredes, Roger; Marcos, M Ángeles; Manzardo, Christian; Moreno, Asunción; Miró, José M

    2015-08-01

    HIV-1 is the most prevalent retrovirus, with over 30 million people infected worldwide. Nevertheless, infection caused by other human retroviruses like HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4 is gaining importance. Initially confined to specific geographical areas, HIV-2, HTLV-1 and HTLV-2 are becoming a major concern in non-endemic countries due to international migration flows. Clinical manifestations of retroviruses range from asymptomatic carriers to life-threatening conditions, such as AIDS in HIV-2 infection or adult T-cell lymphoma/leukemia or tropical spastic paraparesis in HTLV-1 infection. HIV-2 is naturally resistant to some antiretrovirals frequently used to treat HIV-1 infection, but it does have effective antiretroviral therapy options. Unfortunately, HTLV still has limited therapeutic options. In this article, we will review the epidemiological, clinical, diagnostic, pathogenic and therapeutic aspects of infections caused by these human retroviruses.

  4. Suboptimal porcine endogenous retrovirus infection in non-human primate cells: implication for preclinical xenotransplantation.

    Directory of Open Access Journals (Sweden)

    Giada Mattiuzzo

    Full Text Available BACKGROUND: Porcine endogenous retrovirus (PERV poses a potential risk of zoonotic infection in xenotransplantation. Preclinical transplantation trials using non-human primates (NHP as recipients of porcine xenografts present the opportunity to assess the zoonosis risk in vivo. However, PERV poorly infects NHP cells for unclear reasons and therefore NHP may represent a suboptimal animal model to assess the risk of PERV zoonoses. We investigated the mechanism responsible for the low efficiency of PERV-A infection in NHP cells. PRINCIPAL FINDINGS: Two steps, cell entry and exit, were inefficient for the replication of high-titer, human-tropic A/C recombinant PERV. A restriction factor, tetherin, is likely to be responsible for the block to matured virion release, supported by the correlation between the levels of inhibition and tetherin expression. In rhesus macaque, cynomolgus macaque and baboon the main receptor for PERV entry, PERV-A receptor 1 (PAR-1, was found to be genetically deficient: PAR-1 genes in these species encode serine at amino acid 109 in place of the leucine in human PAR-1. This genetic defect inevitably impacts in vivo sensitivity to PERV infection of these species. In contrast, African green monkey (AGM PAR-1 is functional, but PERV infection is still poor. Although the mechanism is unclear, tunicamycin treatment, which removes N-glycosylated sugar chains, increases PERV infection, suggesting a possible role for the glycosylation of the receptors. CONCLUSIONS: Since cynomolgus macaque and baboon, species often used in pig-to-NHP xenotransplantation experiments, have a defective PAR-1, they hardly represent an ideal animal model to assess the risk of PERV transmission in xenotransplantation. Alternatively, NHP species, like AGM, whose both PARs are functional may represent a better model than baboon and cynomolgus macaque for PERV zoonosis in vivo studies.

  5. Susceptibility of human liver cells to porcine endogenous retrovirus.

    Science.gov (United States)

    Lin, Xinzi; Qi, Lin; Li, Zhiguo; Chi, Hao; Lin, Wanjun; Wang, Yan; Jiang, Zesheng; Pan, Mingxin; Gao, Yi

    2013-12-01

    The risk of porcine endogenous retrovirus infection is a major barrier for pig-to-human xenotransplant. Porcine endogenous retrovirus, present in porcine cells, can infect many human and nonhuman primate cells in vitro, but there is no evidence available about in vitro infection of human liver cells. We investigated the susceptibility of different human liver cells to porcine endogenous retrovirus. The supernatant from a porcine kidney cell line was added to human liver cells, including a normal hepatocyte cell line (HL-7702 cells), primary hepatocytes (Phh cells), and a liver stellate cell line (Lx-2 cells), and to human embryonic kidney cells as a reference control. Expression of the porcine endogenous retrovirus antigen p15E in the human cells was evaluated with polymerase chain reaction, reverse transcription-polymerase chain reaction, and Western blot. The porcine endogenous retrovirus antigen p15E was not expressed in any human liver cells (HL-7702, Phh, or Lx-2 cells) that had been exposed to supernatants from porcine kidney cell lines. Porcine endogenous retrovirus-specific fragments were amplified in human kidney cells. Human liver cells tested were not susceptible to infection by porcine endogenous retrovirus. Therefore, not all human cells are susceptible to porcine endogenous retrovirus.

  6. Human retroviruses and AIDS 1994

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    Myers, G.; Korber, B. [Los Alamos National Lab., NM (United States); Wain-Hobson, S.; Jeang, Kuan-Teh; Henderson, L.E.; Pavlakis, G.N. [eds.

    1995-01-01

    This compendium, including accompanying floppy diskettes, is the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts it comprises: (I) Nucleic Acid Alignments and Sequences; (II) Amino Acid Alignments; (III) Analysis; (IV) Related Sequences; (V) Database communications.

  7. Retroviruses.

    Science.gov (United States)

    Varmus, Harold

    1988-01-01

    Discusses the growth, development, and unusual parasitic nature of the retrovirus community. Reviews these infectious cancer-causing agents as models for the study of fundamental biological problems, tools for genetic manipulations, and problems posed by their pathogenic potential in humans and animal hosts where they cause diseases such as…

  8. Human retroviruses and AIDS 1997

    Energy Technology Data Exchange (ETDEWEB)

    Korber, B.; Foley, B.; Leitner, T. [eds.] [and others

    1997-12-01

    This compendium is the result of an effort to compile, organize, and rapidly publish as much relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses as possible. The scope of the compendium and database is best summarized by the four parts that it comprises: (1) Nucleic Acid Alignments, (2) Amino Acid Alignments, (3) Reviews and Analyses, and (4) Related Sequences. Information within all the parts is updated throughout the year on the Web site, http://hiv-web.lanl.gov. This year we are not including floppy diskettes as the entire compendium is available both at our Web site and at our ftp site. If you need floppy diskettes please contact either Bette Korber (btk@t10.lanl.gov) or Kersti Rock (karm@t10.lanl.gov) by email or fax ((505) 665-4453). While this publication could take the form of a review or sequence monograph, it is not so conceived. Instead, the literature from which the database is derived has simply been summarized and some elementary computational analyses have been performed upon the data. Interpretation and commentary have been avoided insofar as possible so that the reader can form his or her own judgments concerning the complex information. The exception to this are reviews submitted by experts in areas deemed of particular and basic importance to research involving AIDS viral sequence information. These are included in Part III, and are contributed by scientists with particular expertise in the area of interest. In addition to the general descriptions below of the parts of the compendium, the user should read the individual introductions for each part.

  9. Vaccination against feline retrovirus infections

    NARCIS (Netherlands)

    Horzinek, M.C.

    1996-01-01

    Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV), both of veterinary importance, their antigenic and genetic variability as well as their pathogenicity are described. Disease following FeLV infection is interpreted as a consequence of genetic recombination, as a result of viral

  10. Human retroviruses in Amerindians of Colombia: high prevalence of human T cell lymphotropic virus type II infection among the Tunebo Indians.

    Science.gov (United States)

    Duenas-Barajas, E; Bernal, J E; Vaught, D R; Nerurkar, V R; Sarmiento, P; Yanagihara, R; Gajdusek, D C

    1993-12-01

    The coexistence of infection with human T lymphotropic virus types I and II (HTLV-I and HTLV-II) has been demonstrated recently among the Wayuu Indians from the Guajira region of Colombia. To ascertain if other Indian groups in Colombia are similarly infected, we tested 1,250 sera, collected between 1990 and 1992 from 18 culturally distinct Amerindian tribes living in widely separated regions, for IgG antibodies against HTLV-I/II using enzyme-linked immunosorbent assay (ELISA) and Western blot. Sera were also tested for antibodies against human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) to investigate the overall burden of retrovirus infection in these semi-isolated indigenous groups. A total of 33 of the 1,250 samples were repeatedly reactive to HTLV-I/II antigens by ELISA, and of these, three sera from Waunana/Noanama Indians from the Choco area and two sera from Tunebo Indians from the Santander region were found to be infected with HTLV-I and HTLV-II, respectively, as verified by Western blot and differential ELISA. Thus, despite the small sample size, the overall seroprevalences for HTLV-I and HTLV-II infection among the Waunana/Noanama and Tunebo Indians were 2.1% and 5.0%, respectively. In contrast, none of the 29 Indians who exhibited reactivity to HIV-1/2 by ELISA were seropositive by Western blot. This study adds the Tunebo to the expanding list of Amerindian groups with high prevalences of HTLV-II infection. Further intensive investigations of such indigenous populations will clarify the natural history and disease potential of HTLV-II infection.

  11. Human endogenous retrovirus K(HML-2) Gag- and Env-specific T-cell responses are infrequently detected in HIV-1-infected subjects using standard peptide matrix-based screening

    NARCIS (Netherlands)

    R.B. Jones (R. Brad); V.M. John (Vivek); D.V. Hunter (Diana); E. Martin (Eric); S. Mujib (Shariq); V. Mihajlovic (Vesna); P.C. Burgers (Peter); T.M. Luider (Theo); G. Gyenes (Gabor); N.C. Sheppard (Neil); D. SenGupta (Devi); R. Tandon (Ravi); F.-Y. Yue (Feng-Yun); W.S. Benko (William); C. Kovacs (Carrie); R. Nixon; M.A. Ostrowski (Mario)

    2012-01-01

    textabstractT-cell responses to human endogenous retrovirus (HERV) K(HML-2) Gag and Env were mapped in HIV-1-infected subjects using 15mer peptides. Small peptide pools and high concentrations were used to maximize sensitivity. In the 23 subjects studied, only three bona fide HERV-K(HML-2)-specific

  12. Insufficient natural killer cell responses against retroviruses: how to improve NK cell killing of retrovirus-infected cells.

    Science.gov (United States)

    Littwitz-Salomon, Elisabeth; Dittmer, Ulf; Sutter, Kathrin

    2016-11-08

    Natural killer (NK) cells belong to the innate immune system and protect against cancers and a variety of viruses including retroviruses by killing transformed or infected cells. They express activating and inhibitory receptors on their cell surface and often become activated after recognizing virus-infected cells. They have diverse antiviral effector functions like the release of cytotoxic granules, cytokine production and antibody dependent cellular cytotoxicity. The importance of NK cell activity in retroviral infections became evident due to the discovery of several viral strategies to escape recognition and elimination by NK cells. Mutational sequence polymorphisms as well as modulation of surface receptors and their ligands are mechanisms of the human immunodeficiency virus-1 to evade NK cell-mediated immune pressure. In Friend retrovirus infected mice the virus can manipulate molecular or cellular immune factors that in turn suppress the NK cell response. In this model NK cells lack cytokines for optimal activation and can be functionally suppressed by regulatory T cells. However, these inhibitory pathways can be overcome therapeutically to achieve full activation of NK cell responses and ultimately control dissemination of retroviral infection. One effective approach is to modulate the crosstalk between NK cells and dendritic cells, which produce NK cell-stimulating cytokines like type I interferons (IFN), IL-12, IL-15, and IL-18 upon retrovirus sensing or infection. Therapeutic administration of IFNα directly increases NK cell killing of retrovirus-infected cells. In addition, IL-2/anti-IL-2 complexes that direct IL-2 to NK cells have been shown to significantly improve control of retroviral infection by NK cells in vivo. In this review, we describe novel approaches to improve NK cell effector functions in retroviral infections. Immunotherapies that target NK cells of patients suffering from viral infections might be a promising treatment option for the

  13. Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

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    Tönjes, Ralf R.

    2012-01-01

    Summary: Xenotransplantation may be a solution to overcome the shortage of organs for the treatment of patients with organ failure, but it may be associated with the transmission of porcine microorganisms and the development of xenozoonoses. Whereas most microorganisms may be eliminated by pathogen-free breeding of the donor animals, porcine endogenous retroviruses (PERVs) cannot be eliminated, since these are integrated into the genomes of all pigs. Human-tropic PERV-A and -B are present in all pigs and are able to infect human cells. Infection of ecotropic PERV-C is limited to pig cells. PERVs may adapt to host cells by varying the number of LTR-binding transcription factor binding sites. Like all retroviruses, they may induce tumors and/or immunodeficiencies. To date, all experimental, preclinical, and clinical xenotransplantations using pig cells, tissues, and organs have not shown transmission of PERV. Highly sensitive and specific methods have been developed to analyze the PERV status of donor pigs and to monitor recipients for PERV infection. Strategies have been developed to prevent PERV transmission, including selection of PERV-C-negative, low-producer pigs, generation of an effective vaccine, selection of effective antiretrovirals, and generation of animals transgenic for a PERV-specific short hairpin RNA inhibiting PERV expression by RNA interference. PMID:22491774

  14. Human retroviruses and AIDS, 1991. [CONTAINS GLOSSARY

    Energy Technology Data Exchange (ETDEWEB)

    Myers, G.; Korber, B. (eds.) (Los Alamos National Lab., NM (USA)); Berzofsky, J.A.; Pavlakis, G.N. (eds.) (National Cancer Inst., Bethesda, MD (USA)); Smith, R.F. (ed.) (Harvard Univ. (USA))

    1991-05-01

    This compendium and the accompanying floppy diskettes are the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses.The scope of the compendium and database is best summarized by the five parts that it comprises: (1) HIV and SIV Nucleotide Sequences; (2) Amino Acid Sequences; (3) Analyses; (4) Related Sequences; and (5) Database Communications. Information within all the parts is updated at least twice in each year, which accounts for the modes of binding and pagination in the compendium.

  15. Genomic Flexibility of Human Endogenous Retrovirus Type K

    Science.gov (United States)

    Dube, Derek; Contreras-Galindo, Rafael; He, Shirley; King, Steven R.; Gonzalez-Hernandez, Marta J.; Gitlin, Scott D.; Kaplan, Mark H.

    2014-01-01

    ABSTRACT Human endogenous retrovirus type K (HERV-K) proviruses are scattered throughout the human genome, but as no infectious HERV-K virus has been detected to date, the mechanism by which these viruses replicated and populated the genome remains unresolved. Here, we provide evidence that, in addition to the RNA genomes that canonical retroviruses package, modern HERV-K viruses can contain reverse-transcribed DNA (RT-DNA) genomes. Indeed, reverse transcription of genomic HERV-K RNA into the DNA form is able to occur in three distinct times and locations: (i) in the virus-producing cell prior to viral release, yielding a DNA-containing extracellular virus particle similar to the spumaviruses; (ii) within the extracellular virus particle itself, transitioning from an RNA-containing particle to a DNA-containing particle; and (iii) after entry of the RNA-containing virus into the target cell, similar to canonical retroviruses, such as murine leukemia virus and HIV. Moreover, using a resuscitated HERV-K virus construct, we show that both viruses with RNA genomes and viruses with DNA genomes are capable of infecting target cells. This high level of genomic flexibility historically could have permitted these viruses to replicate in various host cell environments, potentially assisting in their many integration events and resulting in their high prevalence in the human genome. Moreover, the ability of modern HERV-K viruses to proceed through reverse transcription and package RT-DNA genomes suggests a higher level of replication competency than was previously understood, and it may be relevant in HERV-K-associated human diseases. IMPORTANCE Retroviral elements comprise at least 8% of the human genome. Of all the endogenous retroviruses, HERV-K viruses are the most intact and biologically active. While a modern infectious HERV-K has yet to be found, HERV-K activation has been associated with cancers, autoimmune diseases, and HIV-1 infection. Thus, determining how this

  16. Origin and diversity of human retroviruses

    OpenAIRE

    Peeters, Martine; D'Arc, M.; Delaporte, Eric

    2014-01-01

    Simian immunodeficiency viruses, simian T-cell lymphotropic viruses, and simian foamy viruses from nonhuman primates have crossed the species barrier to humans at several time points, leading to the HIV and human T lymphotropic virus epidemic and to sporadic cases of human infections with simian foamy viruses, respectively. Efficient infection and spread in humans differs between simian foamy virus, simian lymphotropic virus, and simian immunodeficiency virus, but seems also to differ among t...

  17. Apparatus for testing for infection by a retrovirus

    Science.gov (United States)

    Layne, Scott P.; Beugelsdijk, Tony J.

    1999-01-01

    An apparatus for testing specimens for infection by a retrovirus is described. The apparatus comprises a process controller including a communications module for translating user commands into test instrument suite commands and a means for communicating specimen test results to a user. The apparatus further comprises a test instrument suite including a means for treating the specimen to manifest an observable result and a detector for measuring the observable result.

  18. Flow cytometric assay detecting cytotoxicity against human endogenous retrovirus antigens expressed on cultured multiple sclerosis cells

    DEFF Research Database (Denmark)

    Møller-Larsen, A; Brudek, T; Petersen, T

    2013-01-01

    expressing increased amounts of human endogenous retrovirus antigens. MS patients also have increased antibody levels to these antigens. The target cells are spontaneously growing peripheral blood mononuclear cells (PBMCs) of B cell lineage, expressing human endogenous retrovirus HERV epitopes...

  19. Evaluation of Vero-cell-derived simian endogenous retrovirus infection in humans by detection of viral genome in clinicopathological samples and commercialized vaccines and by serology of Japanese general population.

    Science.gov (United States)

    Fukumoto, Hitomi; Hishima, Tsunekazu; Hasegawa, Hideki; Saeki, Hidehisa; Kuroda, Makoto; Katano, Harutaka

    2016-05-23

    Vero cells are used in laboratories for the isolation of viruses and the production of vaccines. Recently, the sequence of simian endogenous retrovirus (SERV) was identified in Vero cells (SERVagm-Vero), with homology to exogenously transmitted, pathogenic simian retroviruses (SRVs). Although SERVagm-Vero was shown to be noninfectious to human cells in vitro, SERV infection in humans is controversial. In this study, we evaluated the status of SERV infection in humans by detecting the viral genome in clinicopathological samples and commercialized vaccines, and with a serological survey of the Japanese general population. Real-time polymerase chain reaction (PCR) and reverse transcription-PCR were used to detect the SERVagm-Vero genome. We also examined the seroprevalence of SERV in 1000 individuals in the Japanese population with an enzyme-linked immunoabsorbent assay (ELISA) using mixed SERVagm-Vero gag, pol, and env proteins as antigens. Real-time PCR failed to detect SERVagm-Vero genomic fragments in 783 human clinicopathological samples, and all 13 human cell lines tested were negative for the SERVagm-Vero genome. Thirteen commercialized vaccines, including five Vero-based vaccines, were also negative for the SERVagm-Vero genome on real-time PCR and reverse transcription-PCR. Eight (0.8%) were seropositive on ELISA, and western blotting showed that all eight sera contained anti-pol antibodies. All SERV-seropositive individuals were born before 1965, suggesting that SERV infection in Japan might not be associated with vaccine, because more than 90% of Japanese children born from 1964 to 2012 have received live poliovirus vaccines containing virus produced in Vero cells since the 1980s. We have confirmed that the vaccines we use today are free of SERVagm-Vero. Moreover, SERV infection in humans is very rare and unlikely to be associated with vaccines in the Japanese general population. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Efficacy of antiviral chemotherapy for retrovirus-infected cats: What does the current literature tell us?

    Science.gov (United States)

    Hartmann, Katrin

    2015-11-01

    The two feline retroviruses, feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV), are global and widespread, but differ in their potential to cause disease. FIV, a lentivirus that shares many properties with human immunodeficiency virus (HIV), can cause an acquired immune deficiency syndrome, which predisposes cats to other infections, stomatitis, neurological disorders and tumours. Although secondary infections are common, specific opportunistic infections or acquired immunodeficiency virus-defining infections, such as those that occur with HIV, are not commonly reported in FIV-infected cats. In most naturally infected cats, FIV does not cause a severe clinical syndrome; with appropriate care, FIV-infected cats can live many years before succumbing to conditions unrelated to their FIV infection. Thus, overall survival time is not necessarily shorter than in uninfected cats, and quality of life is usually high over many years or lifelong. FeLV, an oncornavirus, is more pathogenic than FIV. Historically, it was considered to account for more disease-related deaths and clinical syndromes in cats than any other infectious agent. Recently, the prevalence and importance of FeLV have been decreasing, mainly because of testing and eradication programmes and the use of FeLV vaccines. Progressive FeLV infection can cause tumours, bone marrow suppression and immunosuppression, as well as neurological and other disorders, and leads to a decrease in life expectancy. However, with appropriate care, many FeLV-infected cats can also live several years with a good quality of life. A decision regarding treatment or euthanasia should never be based solely on the presence or absence of a retrovirus infection. Antiviral chemotherapy is of increasing interest in veterinary medicine, but is still not used commonly. This article reviews the current literature on antiviral chemotherapy in retrovirus-infected cats, focusing on drugs that are currently available on the

  1. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...... factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...

  2. Investigation of Human Cancers for Retrovirus by Low-Stringency Target Enrichment and High-Throughput Sequencing

    DEFF Research Database (Denmark)

    Vinner, Lasse; Mourier, Tobias; Friis-Nielsen, Jens

    2015-01-01

    sequences in clinical samples. We used this method to conduct an investigation for novel retrovirus in samples from three cancer types. In accordance with recent studies our investigation revealed no retroviral infections in human B-cell lymphoma cells, cutaneous T-cell lymphoma or colorectal cancer...

  3. RNA levels of human retrovirus receptors Pit1 and Pit2 do not correlate with infectibility by three retroviral vector pseudotypes

    DEFF Research Database (Denmark)

    Uckert, Wolfgang; Willimsky, Gerald; Pedersen, Finn Skou

    1998-01-01

    cell line it used Pit1 more efficiently for entry. We conclude that (1) Pit1 and Pit2 mRNA levels in human cells are not indicative of the infectibility by GaLV and A-MuLV pseudotypes, respectively; (2) A-MuLV can infect target cells as efficiently as can GaLV, although Pit2 RNA is less abundant than......The gibbon ape leukemia virus (GaLV) and the amphotropic murine leukemia virus (A-MuLV) infect human cells via specific receptors, Pit1 and Pit2, respectively. mRNA levels of these receptors were determined by Northern analysis and for Pit2 in addition by quantitative RT-PCR. Pit1 and Pit2 were...... expressed in different amounts in human tissues and cell lines; Pit1-specific mRNA was generally more abundant than Pit2 mRNA. No correlation was found between Pit1 and Pit2 RNA levels and infectibility by GaLV and A-MuLV pseudotyped vectors, respectively. GaLV and A-MuLV revealed a partial reciprocal...

  4. Evolutionary history of the human endogenous retrovirus family ERV9.

    Science.gov (United States)

    Costas, J; Naveira, H

    2000-02-01

    Several distinct families of endogenous retrovirus-like elements (ERVs) exist in the genomes of primates. Despite the important evolutionary consequences that carrying these intragenomic parasites may have for their hosts, our knowledge about their evolution is still scarce. A matter of particular interest is whether evolution of ERVs occurs via a master lineage or through several lineages coexisting over long periods of time. In this work, the paleogenomic approach has been applied to the study of the evolution of ERV9, one of the human endogenous retrovirus families mobilized during primate evolution. By searching the GenBank database with the first 676 bp of the ERV9 long terminal repeat, we identified 156 different element insertions into the human genome. These elements were grouped into 14 subfamilies based on several characteristic nucleotide differences. The age of each subfamily was roughly estimated based on the average sequence divergence of its members from the subfamily consensus sequence. Determination of the sequential order of diagnostic substitutions led to the identification of four distinct lineages, which retained their capacity of transposition over extended periods of evolution. Strong evidence for mosaic evolution of some of these lineages is presented. Taken altogether, the available data indicate that the possibility of ERV9 still being active in the human lineage can not be discarded.

  5. Human Endogenous Retrovirus W Activity in Cartilage of Osteoarthritis Patients

    Directory of Open Access Journals (Sweden)

    Signy Bendiksen

    2014-01-01

    Full Text Available The etiology of viruses in osteoarthritis remains controversial because the prevalence of viral nucleic acid sequences in peripheral blood or synovial fluid from osteoarthritis patients and that in healthy control subjects are similar. Until now the presence of virus has not been analyzed in cartilage. We screened cartilage and chondrocytes from advanced and non-/early osteoarthritis patients for parvovirus B19, herpes simplex virus-1, Epstein Barr virus, cytomegalovirus, human herpes virus-6, hepatitis C virus, and human endogenous retroviruses transcripts. Endogenous retroviruses transcripts, but none of the other viruses, were detected in 15 out the 17 patients. Sequencing identified the virus as HERV-WE1 and E2. HERV-W activity was confirmed by high expression levels of syncytin, dsRNA, virus budding, and the presence of virus-like particles in all advanced osteoarthritis cartilages examined. Low levels of HERV-WE1, but not E2 envelope RNA, were observed in 3 out of 8 non-/early osteoarthritis patients, while only 3 out of 7 chondrocytes cultures displayed low levels of syncytin, and just one was positive for virus-like particles. This study demonstrates for the first time activation of HERV-W in cartilage of osteoarthritis patients; however, a causative role for HERV-W in development or deterioration of the disease remains to be proven.

  6. Innate immunity in the pathogenesis of polytropic retrovirus infection in the central nervous system.

    Science.gov (United States)

    Peterson, Karin E; Du, Min

    2009-01-01

    Neuroinflammation, including astrogliosis, microgliosis, and the production of proinflammatory cytokines and chemokines is a common response in the central nervous system (CNS) to virus infection, including retrovirus infection. However, the contribution of this innate immune response in disease pathogenesis remains unresolved. Analysis of the neuroinflammatory response to polytropic retrovirus infection in the mouse has provided insight into the potential contribution of the innate immune response to retrovirus-induced neurologic disease. In this model, retroviral pathogenesis correlates with the induction of neuroinflammatory responses including the activation of astrocytes and microglia, as well as the production of proinflammatory cytokines and chemokines. Studies of the neurovirulent determinants of the polytropic envelope protein as well as studies with knockout mice suggest that retroviral pathogenesis in the brain is multifaceted and that cytokine and chemokine production may be only one mechanism of disease pathogenesis. Analysis of the activation of the innate immune response to retrovirus infection in the CNS indicates that toll-like receptor 7 (TLR7) is a contributing factor to retrovirus-induced neuroinflammation, but that other factors can compensate for the lack of TLR7 in inducing both neuroinflammation and neurologic disease.

  7. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection.

    Science.gov (United States)

    Li, Sam X; Barrett, Bradley S; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L

    2016-02-05

    Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation.

  8. Endogenous retroviruses in fish genomes: from relics of past infections to evolutionary innovations?

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    Magali Naville

    2016-08-01

    Full Text Available The increasing availability of fish genome sequences has allowed to gain new insights into the diversity and host distribution of retroviruses in fish and other vertebrates. This distribution can be assessed through the identification and analysis of endogenous retroviruses, which are proviral remnants of past infections integrated in genomes. Retroviral sequences are probably important for evolution through their ability to induce rearrangements and to contribute regulatory and coding sequences; they may also protect their host against new infections. We argue that the current mass of genome sequences will soon strongly improve our understanding of retrovirus diversity and evolution in aquatic animals, with the identification of new/re-emerging elements and host resistance genes that restrict their infectivity.

  9. Evidence against a role for jaagsiekte sheep retrovirus in human lung cancer.

    Science.gov (United States)

    Miller, A Dusty; De Las Heras, Marcelo; Yu, Jingyou; Zhang, Fushun; Liu, Shan-Lu; Vaughan, Andrew E; Vaughan, Thomas L; Rosadio, Raul; Rocca, Stefano; Palmieri, Giuseppe; Goedert, James J; Fujimoto, Junya; Wistuba, Ignacio I

    2017-01-20

    Jaagsiekte sheep retrovirus (JSRV) causes a contagious lung cancer in sheep and goats that can be transmitted by aerosols produced by infected animals. Virus entry into cells is initiated by binding of the viral envelope (Env) protein to a specific cell-surface receptor, Hyal2. Unlike almost all other retroviruses, the JSRV Env protein is also a potent oncoprotein and is responsible for lung cancer in animals. Of concern, Hyal2 is a functional receptor for JSRV in humans. We show here that JSRV is fully capable of infecting human cells, as measured by its reverse transcription and persistence in the DNA of cultured human cells. Several studies have indicated a role for JSRV in human lung cancer while other studies dispute these results. To further investigate the role of JSRV in human lung cancer, we used highly-specific mouse monoclonal antibodies and a rabbit polyclonal antiserum against JSRV Env to test for JSRV expression in human lung cancer. JSRV Env expression was undetectable in lung cancers from 128 human subjects, including 73 cases of bronchioalveolar carcinoma (BAC; currently reclassified as lung invasive adenocarcinoma with a predominant lepidic component), a lung cancer with histology similar to that found in JSRV-infected sheep. The BAC samples included 8 JSRV DNA-positive samples from subjects residing in Sardinia, Italy, where sheep farming is prevalent and JSRV is present. We also tested for neutralizing antibodies in sera from 138 Peruvians living in an area where sheep farming is prevalent and JSRV is present, 24 of whom were directly exposed to sheep, and found none. We conclude that while JSRV can infect human cells, JSRV plays little if any role in human lung cancer.

  10. Seroprevalence of xenotropic murine leukemia virus-related virus in normal and retrovirus-infected blood donors.

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    Qiu, Xiaoxing; Swanson, Priscilla; Tang, Ning; Leckie, Gregor W; Devare, Sushil G; Schochetman, Gerald; Hackett, John

    2012-02-01

    Xenotropic murine leukemia virus-related virus (XMRV) has been reported in patients with prostate cancer and chronic fatigue syndrome. Although results have been conflicting, the potential of XMRV as an infectious human retrovirus has raised concerns about transfusion safety. To address this issue, normal and retrovirus-infected blood donors were screened for evidence of XMRV infection. Plasma from 1000 US, 100 human immunodeficiency virus Type 1-infected Cameroonian, and 642 human T-lymphotropic virus Type I (HTLV-I)-infected or uninfected Japanese blood donors as well as 311 sexually transmitted disease diagnostic specimens were screened for antibodies to XMRV gp70 and p15E using chemiluminescent immunoassays (CMIAs). CMIA-reactive samples were evaluated by p30 CMIA, Western blot, and real-time reverse transcriptase polymerase chain reaction. XMRV seroreactivity was low (0%-0.6%) with the exception of the HTLV-I-infected donors (4.9%). Antibody was detected against only a single XMRV protein (p15E or gp70); none of the seroreactive samples had detectable XMRV pol or env sequences. The elevated seroreactivity in HTLV-I-infected donors was due to an increased p15E seroreactive rate (4.1%). Inspection of XMRV and HTLV sequences revealed a high level of conservation within the immunodominant region (IDR) of the transmembrane protein. In some cases, HTLV IDR peptide competitively reduced the XMRV p15E signal. Based on the low prevalence of seroreactivity, detection of antibody to only a single XMRV protein and the absence of XMRV sequences, this study finds no compelling evidence of XMRV in normal or retrovirus-infected blood donors. The increased p15E seroreactivity observed in HTLV infection is likely due to cross-reactive antibodies. © 2012 American Association of Blood Banks.

  11. Different modes of retrovirus restriction by human APOBEC3A and APOBEC3G in vivo.

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    Stavrou, Spyridon; Crawford, Daniel; Blouch, Kristin; Browne, Edward P; Kohli, Rahul M; Ross, Susan R

    2014-05-01

    The apolipoprotein B editing complex 3 (A3) cytidine deaminases are among the most highly evolutionarily selected retroviral restriction factors, both in terms of gene copy number and sequence diversity. Primate genomes encode seven A3 genes, and while A3F and 3G are widely recognized as important in the restriction of HIV, the role of the other genes, particularly A3A, is not as clear. Indeed, since human cells can express multiple A3 genes, and because of the lack of an experimentally tractable model, it is difficult to dissect the individual contribution of each gene to virus restriction in vivo. To overcome this problem, we generated human A3A and A3G transgenic mice on a mouse A3 knockout background. Using these mice, we demonstrate that both A3A and A3G restrict infection by murine retroviruses but by different mechanisms: A3G was packaged into virions and caused extensive deamination of the retrovirus genomes while A3A was not packaged and instead restricted infection when expressed in target cells. Additionally, we show that a murine leukemia virus engineered to express HIV Vif overcame the A3G-mediated restriction, thereby creating a novel model for studying the interaction between these proteins. We have thus developed an in vivo system for understanding how human A3 proteins use different modes of restriction, as well as a means for testing therapies that disrupt HIV Vif-A3G interactions.

  12. The retrovirus HTLV-1 inserts an ectopic CTCF-binding site into the human genome.

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    Satou, Yorifumi; Miyazato, Paola; Ishihara, Ko; Yaguchi, Hiroko; Melamed, Anat; Miura, Michi; Fukuda, Asami; Nosaka, Kisato; Watanabe, Takehisa; Rowan, Aileen G; Nakao, Mitsuyoshi; Bangham, Charles R M

    2016-03-15

    Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes malignant and inflammatory diseases in ∼10% of infected people. A typical host has between 10(4) and 10(5) clones of HTLV-1-infected T lymphocytes, each clone distinguished by the genomic integration site of the single-copy HTLV-1 provirus. The HTLV-1 bZIP (HBZ) factor gene is constitutively expressed from the minus strand of the provirus, whereas plus-strand expression, required for viral propagation to uninfected cells, is suppressed or intermittent in vivo, allowing escape from host immune surveillance. It remains unknown what regulates this pattern of proviral transcription and latency. Here, we show that CTCF, a key regulator of chromatin structure and function, binds to the provirus at a sharp border in epigenetic modifications in the pX region of the HTLV-1 provirus in T cells naturally infected with HTLV-1. CTCF is a zinc-finger protein that binds to an insulator region in genomic DNA and plays a fundamental role in controlling higher order chromatin structure and gene expression in vertebrate cells. We show that CTCF bound to HTLV-1 acts as an enhancer blocker, regulates HTLV-1 mRNA splicing, and forms long-distance interactions with flanking host chromatin. CTCF-binding sites (CTCF-BSs) have been propagated throughout the genome by transposons in certain primate lineages, but CTCF binding has not previously been described in present-day exogenous retroviruses. The presence of an ectopic CTCF-BS introduced by the retrovirus in tens of thousands of genomic locations has the potential to cause widespread abnormalities in host cell chromatin structure and gene expression.

  13. The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome.

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    Silverman, Robert H; Nguyen, Carvell; Weight, Christopher J; Klein, Eric A

    2010-07-01

    Xenotropic murine leukemia virus-related virus (XMRV) is an authentic, newly recognized human retrovirus first identified in prostate cancer tissues from men with a deficiency in the innate immunity gene RNASEL. At present, studies have detected XMRV at widely different rates in prostate cancer cases (0-27%) and in patients with chronic fatigue syndrome (CFS; 0-67%). Indirect or direct modes of carcinogenesis by XMRV have been suggested depending on whether the virus was found in stroma or malignant epithelium. Viral replication in the prostate might be affected by androgens, which stimulate XMRV through a transcriptional enhancer site in viral DNA. By contrast, host restriction factors, such as APOBEC3 and tetherin, inhibit virus replication. Immune dysfunction mediated by XMRV has been suggested as a possible factor in CFS. Recent studies show that some existing antiretroviral drugs suppress XMRV infections and diagnostic assays are under development. Although other retroviruses of the same genus as XMRV (gammaretroviruses) cause cancer and neurological disease in animals, whether XMRV is a cause of either prostate cancer or CFS remains unknown. Emerging science surrounding XMRV is contributing to our knowledge of retroviral infections while focusing intense interest on two major human diseases.

  14. Felis Catus Gammaherpesvirus 1 DNAemia in Whole Blood from Therapeutically Immunosuppressed or Retrovirus-Infected Cats

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    Alicia J. McLuckie

    2017-03-01

    Full Text Available Gammaherpesviruses are major co-pathogens of human immunodeficiency virus (HIV infection, making the interactions between feline immunodeficiency virus (FIV and Felis catus gammaherpesvirus 1 (FcaGHV1 pertinent to both human and veterinary medical research. FIV-infected cats are at increased risk of FcaGHV1 DNAemia and consistently harbor higher FcaGHV1 loads than FIV-uninfected cats. Whether immune deficiencies unrelated to FIV are associated with similar risks is unknown. Using whole blood FcaGHV1 qPCR, we found no difference in the frequency of DNAemia or DNA load in therapeutically immunosuppressed (P1, n = 18 or feline leukemia virus (FeLV-infected (P2, n = 57 patients compared with age- and sex-matched controls (C1, n = 58; C2, n = 57. In contrast, FIV/FeLV-co-infected cats (P3, n = 5 were at increased risk of FcaGHV1 DNAemia compared to retrovirus uninfected controls (C3, n = 39; p = 0.0068, and had a higher median FcaGHV1 DNA load, although the latter was not significant. FIV/FeLV-co-infected cats (P3 had a similar frequency of FcaGHV1 DNAemia reported compared to FIV-infected controls (C4. In conclusion, we found no evidence that cats with therapeutic immunosuppression or FeLV infection were at greater risk of FcaGHV1 DNAemia or had higher FcaGHV1 DNA load in whole blood. The risk of DNAemia in FIV/FeLV-co-infected cats was similar to that documented previously in cats infected with FIV alone.

  15. Characterization of retroviral infectivity and superinfection resistance during retrovirus-mediated transduction of mammalian cells.

    Science.gov (United States)

    Liao, J; Wei, Q; Fan, J; Zou, Y; Song, D; Liu, J; Liu, F; Ma, C; Hu, X; Li, L; Yu, Y; Qu, X; Chen, L; Yu, X; Zhang, Z; Zhao, C; Zeng, Z; Zhang, R; Yan, S; Wu, T; Wu, X; Shu, Y; Lei, J; Li, Y; Zhang, W; Wang, J; Reid, R R; Lee, M J; Huang, W; Wolf, J M; He, T-C; Wang, J

    2017-06-01

    Retroviral vectors including lentiviral vectors are commonly used tools to stably express transgenes or RNA molecules in mammalian cells. Their utilities are roughly divided into two categories, stable overexpression of transgenes and RNA molecules, which requires maximal transduction efficiency, or functional selection with retrovirus (RV)-based libraries, which takes advantage of retroviral superinfection resistance. However, the dynamic features of RV-mediated transduction are not well characterized. Here, we engineered two murine stem cell virus-based retroviral vectors expressing dual fluorescence proteins and antibiotic markers, and analyzed virion production efficiency and virion stability, dynamic infectivity and superinfection resistance in different cell types, and strategies to improve transduction efficiency. We found that the highest virion production occurred between 60 and 72 h after transfection. The stability of the collected virion supernatant decreased by >60% after 3 days in storage. We found that RV infectivity varied drastically in the tested human cancer lines, while low transduction efficiency was partially overcome with increased virus titer, prolonged infection duration and/or repeated infections. Furthermore, we demonstrated that RV receptors PIT1 and PIT2 were lowly expressed in the analyzed cells, and that PIT1 and/or PIT2 overexpression significantly improved transduction efficiency in certain cell lines. Thus, our findings provide resourceful information for the optimal conditions of retroviral-mediated gene delivery.

  16. Tetherin promotes the innate and adaptive cell-mediated immune response against retrovirus infection in vivo.

    Science.gov (United States)

    Li, Sam X; Barrett, Bradley S; Heilman, Karl J; Messer, Ronald J; Liberatore, Rachel A; Bieniasz, Paul D; Kassiotis, George; Hasenkrug, Kim J; Santiago, Mario L

    2014-07-01

    Tetherin/BST-2 is a host restriction factor that could directly inhibit retroviral particle release by tethering nascent virions to the plasma membrane. However, the immunological impact of Tetherin during retrovirus infection remains unknown. We now show that Tetherin influences antiretroviral cell-mediated immune responses. In contrast to the direct antiviral effects of Tetherin, which are dependent on cell surface expression, the immunomodulatory effects are linked to the endocytosis of the molecule. Mice encoding endocytosis-competent C57BL/6 Tetherin exhibited lower viremia and pathology at 7 d postinfection with Friend retrovirus (FV) compared with mice encoding endocytosis-defective NZW/LacJ Tetherin. Notably, antiretroviral protection correlated with stronger NK cell responses. In addition, Friend retrovirus infection levels were significantly lower in wild-type C57BL/6 mice than in Tetherin knockout mice at 2 wk postinfection, and antiretroviral protection correlated with stronger NK cell and virus-specific CD8+ T cell responses. The results demonstrate that Tetherin acts as a modulator of the cell-mediated immune response against retrovirus infection in vivo.

  17. Epidemiological aspects of retrovirus (HTLV infection among Indian populations in the Amazon Region of Brazil

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    Ishak Ricardo

    2003-01-01

    Full Text Available HTLV was initially described in association with a form of leukemia in Japan and a neurological disease in the Caribbean. It was soon shown that HTLV-II was endemic among Amerindians and particularly among Brazilian Indians. The Amazon Region of Brazil is presently the largest endemic area for this virus and has allowed several studies concerning virus biology, the search for overt disease, epidemiological data including detailed demographic data on infected individuals, clear-cut geographic distribution, definition of modes of transmission and maintenance within small, epidemiologically-closed groups, and advances in laboratory diagnosis of the infection. A new molecular subtype named HTLV-IIc was further described on the basis of genome sequencing and phylogenetic analysis. This subtype is present in other areas of Brazil, indicating that the virus is additionally both a valuable marker for tracing past human migration routes in the Americas and a probable marker for social habits of the present human population. HIV, the other human retrovirus, is still not prevalent among indigenous communities in the Brazilian Amazon, but these groups are also easy targets for the virus.

  18. Implication of Human Endogenous Retrovirus Envelope Proteins in Placental Functions

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    Adjimon Gatien Lokossou

    2014-11-01

    Full Text Available Human endogenous retroviruses (ERVs represent 8% of the total human genome. Although the majority of these ancient proviral sequences have only retained non-coding long terminal repeats (LTRs, a number of “endogenized” retroviral genes encode functional proteins. Previous studies have underlined the implication of these ERV-derived proteins in the development and the function of the placenta. In this review, we summarize recent findings showing that two ERV genes, termed Syncytin-1 and Syncytin-2, which encode former envelope (Env proteins, trigger fusion events between villous cytotrophoblasts and the peripheral multinucleated syncytiotrophoblast layer. Such fusion events maintain the stability of this latter cell structure, which plays an important role in fetal development by the active secretion of various soluble factors, gas exchange and regulation of fetomaternal immunotolerance. We also highlight new studies showing that these ERV proteins, in addition to their localization at the cell surface of cytotrophoblasts, are also incorporated on the surface of various extracellular microvesicles, including exosomes. Such exosome-associated proteins could be involved in the various functions attributed to these vesicles and could provide a form of tropism. Additionally, through their immunosuppressive domains, these ERV proteins could also contribute to fetomaternal immunotolerance in a local and more distal manner. These various aspects of the implication of Syncytin-1 and -2 in placental function are also addressed in the context of the placenta-related disorder, preeclampsia.

  19. Neuropeptide Y Negatively Influences Monocyte Recruitment to the Central Nervous System during Retrovirus Infection.

    Science.gov (United States)

    Woods, Tyson A; Du, Min; Carmody, Aaron; Peterson, Karin E

    2015-12-30

    Monocyte infiltration into the CNS is a hallmark of several viral infections of the central nervous system (CNS), including retrovirus infection. Understanding the factors that mediate monocyte migration in the CNS is essential for the development of therapeutics that can alter the disease process. In the current study, we found that neuropeptide Y (NPY) suppressed monocyte recruitment to the CNS in a mouse model of polytropic retrovirus infection. NPY(-/-) mice had increased incidence and kinetics of retrovirus-induced neurological disease, which correlated with a significant increase in monocytes in the CNS compared to wild-type mice. Both Ly6C(hi) inflammatory and Ly6C(lo) alternatively activated monocytes were increased in the CNS of NPY(-/-) mice following virus infection, suggesting that NPY suppresses the infiltration of both cell types. Ex vivo analysis of myeloid cells from brain tissue demonstrated that infiltrating monocytes expressed high levels of the NPY receptor Y2R. Correlating with the expression of Y2R on monocytes, treatment of NPY(-/-) mice with a truncated, Y2R-specific NPY peptide suppressed the incidence of retrovirus-induced neurological disease. These data demonstrate a clear role for NPY as a negative regulator of monocyte recruitment into the CNS and provide a new mechanism for suppression of retrovirus-induced neurological disease. Monocyte recruitment to the brain is associated with multiple neurological diseases. However, the factors that influence the recruitment of these cells to the brain are still not well understood. In the current study, we found that neuropeptide Y, a protein produced by neurons, affected monocyte recruitment to the brain during retrovirus infection. We show that mice deficient in NPY have increased influx of monocytes into the brain and that this increase in monocytes correlates with neurological-disease development. These studies provide a mechanism by which the nervous system, through the production of NPY

  20. Human and murine APOBEC3s restrict replication of koala retrovirus by different mechanisms.

    Science.gov (United States)

    Nitta, Takayuki; Ha, Dat; Galvez, Felipe; Miyazawa, Takayuki; Fan, Hung

    2015-08-08

    Koala retrovirus (KoRV) is an endogenous and exogenous retrovirus of koalas that may cause lymphoma. As for many other gammaretroviruses, the KoRV genome can potentially encode an alternate form of Gag protein, glyco-gag. In this study, a convenient assay for assessing KoRV infectivity in vitro was employed: the use of DERSE cells (initially developed to search for infectious xenotropic murine leukemia-like viruses). Using infection of DERSE and other human cell lines (HEK293T), no evidence for expression of glyco-gag by KoRV was found, either in expression of glyco-gag protein or changes in infectivity when the putative glyco-gag reading frame was mutated. Since glyco-gag mediates resistance of Moloney murine leukemia virus to the restriction factor APOBEC3, the sensitivity of KoRV (wt or putatively mutant for glyco-gag) to restriction by murine (mA3) or human APOBEC3s was investigated. Both mA3 and hA3G potently inhibited KoRV infectivity. Interestingly, hA3G restriction was accompanied by extensive G → A hypermutation during reverse transcription while mA3 restriction was not. Glyco-gag status did not affect the results. These results indicate that the mechanisms of APOBEC3 restriction of KoRV by hA3G and mA3 differ (deamination dependent vs. independent) and glyco-gag does not play a role in the restriction.

  1. Investigating human T cell lymphotropic retrovirus (HTLV) Tax function with molecular and immunophenotypic techniques.

    Science.gov (United States)

    Forlani, Greta; Accolla, Roberto S; Tosi, Giovanna

    2014-01-01

    Human T cell Lymphotropic Viruses 1 and 2 (HTLV-1 and HTLV-2) are the first described human retroviruses. HTLV-1 is the causative agent of an aggressive malignancy of CD4+ T lymphocytes named adult T-cell leukemia/lymphoma (ATLL) and of a chronic neurological disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-2 shares many similarities with HTLV-1, but displays lower or absent association to diseases. Among the proteins encoded by HTLVs, the viral transactivator Tax exerts an essential role in viral transcription as well as in cell transformation. Different experimental methods to study Tax activity on HTLV-LTR promoter and Tax subcellular distribution are described. Emphasis is given to the functional and physical interaction between Tax-1/Tax-2 and cellular cofactors which may have an impact on the infectivity process of the HTLVs and on the capacity of cell transformation.

  2. Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (Macaca fascicularis

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    Montag Judith

    2011-06-01

    Full Text Available Abstract Background Prion diseases such as bovine spongiform encephalopathies (BSE are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease. Results Cynomolgus macaques (Macaca fasicularis were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2 RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2 Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques. Conclusions We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration.

  3. No association of polymorphisms in human endogenous retrovirus K18 and CD48 with schizophrenia

    DEFF Research Database (Denmark)

    Nyegaard, Mette; Demontis, Ditte; Thestrup, Britta Boserup

    2012-01-01

    The human endogenous retrovirus HERV-K18 is located within intron 1 of CD48 on chromosome 1q and is still active in the human genome. Genetic variation in HERV-K18 single-nucleotide polymorphisms (SNPs) has previously been associated with an increased risk of schizophrenia (SZ) and with type 2...

  4. Human Endogenous Retrovirus HERV-Fc1 Association with Multiple Sclerosis Susceptibility: A Meta-Analysis

    Science.gov (United States)

    García-Montojo, Marta; Alcina, Antonio; Fedetz, María; Alloza, Iraide; Astobiza, Ianire; Leyva, Laura; Fernández, Oscar; Izquierdo, Guillermo; Antigüedad, Alfredo; Arroyo, Rafael; Álvarez-Lafuente, Roberto; Vandenbroeck, Koen; Matesanz, Fuencisla; Urcelay, Elena

    2014-01-01

    Background Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. Methods A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. Results Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: pM-H = 0.0005; ORM-H (95% CI) = 1.27 (1.11–1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [pM-H = 0.0003, ORM-H (95% CI) = 1.32 (1.14–1.53)]. Conclusion Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts. PMID:24594754

  5. 12th international conference on human retrovirology: HTLV and related retroviruses

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    Lairmore Michael D

    2005-10-01

    Full Text Available Abstract The 12th International Conference on Human Retrovirology: HTLV and Related Retroviruses, was held at the Half Moon Hotel in Montego Bay, Jamaica, from June 22nd to June 25th 2005. The scientific conference, sponsored by the International Retrovirology Association, is held biennially at rotating international venues around the world. The meeting brings together basic scientists, epidemiologists and clinical researchers to discuss findings to prevent HTLV infection or develop new therapies against HTLV-mediated diseases. The Association fosters the education and training of young scientists to bring new approaches to the complex problems of HTLV research, such as translational research to bring findings from the laboratory into clinical trials that benefit HTLV-infected patients. The breadth and quality of research presentations and workshops at the 12th International Conference indicate that these goals are being accomplished. As HTLV research enters its third decade a new generation of scientists face many challenges. However, HTLV scientists and clinicians displayed exciting new approaches and discoveries during plenary talks and poster sessions. The conference encouraged research in HTLV infections and disease, fostered collaborations, and stimulated new partnerships between clinicians and scientists to encourage clinical trials and novel therapeutic interventions.

  6. The role of human endogenous retroviruses in brain development and function.

    Science.gov (United States)

    Mortelmans, Kristien; Wang-Johanning, Feng; Johanning, Gary L

    2016-01-01

    Endogenous retroviral sequences are spread throughout the genome of all humans, and make up about 8% of the genome. Despite their prevalence, the function of human endogenous retroviruses (HERVs) in humans is largely unknown. In this review we focus on the brain, and evaluate studies in animal models that address mechanisms of endogenous retrovirus activation in the brain and central nervous system (CNS). One such study in mice found that TRIM28, a protein critical for mouse early development, regulates transcription and silencing of endogenous retroviruses in neural progenitor cells. Another intriguing finding in human brain cells and mouse models was that endogenous retrovirus HERV-K appears to be protective against neurotoxins. We also report on studies that associate HERVs with human diseases of the brain and CNS. There is little doubt of an association between HERVs and a number of CNS diseases. However, a cause and effect relationship between HERVs and these diseases has not yet been established. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  7. Human endogenous retrovirus K and cancer: Innocent bystander or tumorigenic accomplice?

    Science.gov (United States)

    Downey, Ronan F; Sullivan, Francis J; Wang-Johanning, Feng; Ambs, Stefan; Giles, Francis J; Glynn, Sharon A

    2015-09-15

    Harbored as relics of ancient germline infections, human endogenous retroviruses (HERVs) now constitute up to 8% of our genome. A proportion of this sequence has been co-opted for molecular and cellular processes, beneficial to human physiology, such as the fusogenic activity of the envelope protein, a vital component of placentogenesis. However, the discovery of high levels of HERV-K mRNA and protein and even virions in a wide array of cancers has revealed that HERV-K may be playing a more sinister role-a role as an etiological agent in cancer itself. Whether the presence of this retroviral material is simply an epiphenomenon, or an actual causative factor, is a hotly debated topic. This review will summarize the current state of knowledge regarding HERV-K and cancer and attempt to outline the potential mechanisms by which HERV-K could be involved in the onset and promotion of carcinogenesis. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  8. Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors

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    Smith Robert A

    2010-08-01

    Full Text Available Abstract Background XMRV (xenotropic murine leukemia virus-related virus is the first known example of an exogenous gammaretrovirus that can infect humans. A limited number of reports suggest that XMRV is intrinsically resistant to many of the antiretroviral drugs used to treat HIV-1 infection, but is sensitive to a small subset of these inhibitors. In the present study, we used a novel marker transfer assay to directly compare the antiviral drug sensitivities of XMRV and HIV-1 under identical conditions in the same host cell type. Results We extend the findings of previous studies by showing that, in addition to AZT and tenofovir, XMRV and HIV-1 are equally sensitive to AZddA (3'-azido-2',3'-dideoxyadenosine, AZddG (3'-azido-2',3'-dideoxyguanosine and adefovir. These results indicate that specific 3'-azido or acyclic nucleoside analog inhibitors of HIV-1 reverse transcriptase (RT also block XMRV infection with comparable efficacy in vitro. Our data confirm that XMRV is highly resistant to the non-nucleoside RT inhibitors nevirapine and efavirenz and to inhibitors of HIV-1 protease. In addition, we show that the integrase inhibitors raltegravir and elvitegravir are active against XMRV, with EC50 values in the nanomolar range. Conclusions Our analysis demonstrates that XMRV exhibits a distinct pattern of nucleoside analog susceptibility that correlates with the structure of the pseudosugar moiety and that XMRV is sensitive to a broader range of antiretroviral drugs than has previously been reported. We suggest that the divergent drug sensitivity profiles of XMRV and HIV-1 are partially explained by specific amino acid differences in their respective protease, RT and integrase sequences. Our data provide a basis for choosing specific antiretroviral drugs for clinical studies in XMRV-infected patients.

  9. Lack of antiviral antibody response in koalas infected with koala retroviruses (KoRV).

    Science.gov (United States)

    Fiebig, Uwe; Keller, Martina; Möller, Annekatrin; Timms, Peter; Denner, Joachim

    2015-02-16

    Many wild koalas are infected with the koala retrovirus, KoRV, some of which suffer from lymphoma and chlamydial disease. Three subgroups, KoRV-A, KoRV-B and KoRV-J, have so far been described. It is well known that other closely related gammaretroviruses can induce tumours and severe immunodeficiencies in their respective hosts and a possible role for KoRV infection in lymphoma and chlamydial disease in koalas has been suggested. In many wild koalas, KoRV-A has become endogenised, i.e., it is integrated in the germ-line and is passed on with normal cellular genes. In this study, sera from koalas in European zoos and from wild animals in Australia were screened for antibodies against KoRV-A. These naturally infected animals all carry endogenous KoRV-A and two zoo animals are also infected with KoRV-B. The antibody response is generally an important diagnostic tool for detecting retrovirus infections. However, when Western blot analyses were performed using purified virus or recombinant proteins corresponding to KoRV-A, none of the koalas tested positive for specific antibodies, suggesting a state of tolerance. These results have implications for koala vaccination, as they suggest that therapeutic immunisation of animals carrying and expressing endogenous KoRV-A will not be successful. However, it remains unclear whether these animals can be immunised against KoRV-B and immunisation of uninfected koalas could still be worthwhile. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Retroviruses As Myeloid Cell Riders: What Natural Human Siglec-1 “Knockouts” Tell Us About Pathogenesis

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    Javier Martinez-Picado

    2017-11-01

    Full Text Available Myeloid cells initiate immune responses and are crucial to control infections. In the case of retroviruses, however, myeloid cells also promote pathogenesis by enabling viral dissemination; a process extensively studied in vitro using human immunodeficiency virus type 1 (HIV-1. This viral hijacking mechanism does not rely on productive myeloid cell infection but requires HIV-1 capture via Siglec-1/CD169, a receptor expressed on myeloid cells that facilitates the infection of bystander target cells. Murine retroviruses are also recognized by Siglec-1, and this interaction is required for robust retroviral infection in vivo. Yet, the relative contribution of Siglec-1-mediated viral dissemination to HIV-1 disease progression remains unclear. The identification of human null individuals lacking working copies of a particular gene enables studying how this loss affects disease progression. Moreover, it can reveal novel antiviral targets whose blockade might be therapeutically effective and safe, since finding null individuals in natura uncovers dispensable functions. We previously described a loss-of-function variant in SIGLEC-1. Analysis of a large cohort of HIV-1-infected individuals identified homozygous and heterozygous subjects, whose cells were functionally null or partially defective for Siglec-1 activity in HIV-1 capture and transmission ex vivo. Nonetheless, analysis of the effect of Siglec-1 truncation on progression to AIDS was not conclusive due to the limited cohort size, the lack of complete clinical records, and the restriction to study only off-therapy periods. Here, we review how the study of loss-of-function variants might serve to illuminate the role of myeloid cells in viral pathogenesis in vivo and the challenges ahead.

  11. Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus......Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental...... factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...

  12. Integration and Fixation Preferences of Human and Mouse Endogenous Retroviruses Uncovered with Functional Data Analysis.

    Science.gov (United States)

    Campos-Sánchez, Rebeca; Cremona, Marzia A; Pini, Alessia; Chiaromonte, Francesca; Makova, Kateryna D

    2016-06-01

    Endogenous retroviruses (ERVs), the remnants of retroviral infections in the germ line, occupy ~8% and ~10% of the human and mouse genomes, respectively, and affect their structure, evolution, and function. Yet we still have a limited understanding of how the genomic landscape influences integration and fixation of ERVs. Here we conducted a genome-wide study of the most recently active ERVs in the human and mouse genome. We investigated 826 fixed and 1,065 in vitro HERV-Ks in human, and 1,624 fixed and 242 polymorphic ETns, as well as 3,964 fixed and 1,986 polymorphic IAPs, in mouse. We quantitated >40 human and mouse genomic features (e.g., non-B DNA structure, recombination rates, and histone modifications) in ±32 kb of these ERVs' integration sites and in control regions, and analyzed them using Functional Data Analysis (FDA) methodology. In one of the first applications of FDA in genomics, we identified genomic scales and locations at which these features display their influence, and how they work in concert, to provide signals essential for integration and fixation of ERVs. The investigation of ERVs of different evolutionary ages (young in vitro and polymorphic ERVs, older fixed ERVs) allowed us to disentangle integration vs. fixation preferences. As a result of these analyses, we built a comprehensive model explaining the uneven distribution of ERVs along the genome. We found that ERVs integrate in late-replicating AT-rich regions with abundant microsatellites, mirror repeats, and repressive histone marks. Regions favoring fixation are depleted of genes and evolutionarily conserved elements, and have low recombination rates, reflecting the effects of purifying selection and ectopic recombination removing ERVs from the genome. In addition to providing these biological insights, our study demonstrates the power of exploiting multiple scales and localization with FDA. These powerful techniques are expected to be applicable to many other genomic investigations.

  13. DNA hypomethylation and aberrant expression of the human endogenous retrovirus ERVWE1/syncytin-1 in seminomas

    Czech Academy of Sciences Publication Activity Database

    Benešová, Martina; Trejbalová, Kateřina; Kovářová, Denisa; Vernerová, Z.; Hron, Tomáš; Kučerová, Dana; Hejnar, Jiří

    2017-01-01

    Roč. 14, č. 1 (2017), č. článku 20. ISSN 1742-4690 R&D Projects: GA ČR GA13-37600S; GA MZd NT14601 Institutional support: RVO:68378050 Keywords : Human endogenous retrovirus * ERVWE1 * Germ cell tumor * Seminoma * Promoter DNA methylation * 5-Hydroxymethylcytosine * Transcription * RNA splicing Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.867, year: 2016

  14. Investigation of Human Cancers for Retrovirus by Low-Stringency Target Enrichment and High-Throughput Sequencing.

    Science.gov (United States)

    Vinner, Lasse; Mourier, Tobias; Friis-Nielsen, Jens; Gniadecki, Robert; Dybkaer, Karen; Rosenberg, Jacob; Langhoff, Jill Levin; Cruz, David Flores Santa; Fonager, Jannik; Izarzugaza, Jose M G; Gupta, Ramneek; Sicheritz-Ponten, Thomas; Brunak, Søren; Willerslev, Eske; Nielsen, Lars Peter; Hansen, Anders Johannes

    2015-08-19

    Although nearly one fifth of all human cancers have an infectious aetiology, the causes for the majority of cancers remain unexplained. Despite the enormous data output from high-throughput shotgun sequencing, viral DNA in a clinical sample typically constitutes a proportion of host DNA that is too small to be detected. Sequence variation among virus genomes complicates application of sequence-specific, and highly sensitive, PCR methods. Therefore, we aimed to develop and characterize a method that permits sensitive detection of sequences despite considerable variation. We demonstrate that our low-stringency in-solution hybridization method enables detection of retrovirus in samples from three cancer types. In accordance with recent studies our investigation revealed no retroviral infections in human B-cell lymphoma cells, cutaneous T-cell lymphoma or colorectal cancer biopsies. Nonetheless, our generally applicable method makes sensitive detection possible and permits sequencing of distantly related sequences from complex material.

  15. Macroevolution of complex retroviruses.

    Science.gov (United States)

    Katzourakis, Aris; Gifford, Robert J; Tristem, Michael; Gilbert, M Thomas P; Pybus, Oliver G

    2009-09-18

    Retroviruses can leave a "fossil record" in their hosts' genomes in the form of endogenous retroviruses. Foamy viruses, complex retroviruses that infect mammals, have been notably absent from this record. We have found an endogenous foamy virus within the genomes of sloths and show that foamy viruses were infecting mammals more than 100 million years ago and codiverged with their hosts across an entire geological era. Our analysis highlights the role of evolutionary constraint in maintaining viral genome structure and indicates that accessory genes and mammalian mechanisms of innate immunity are the products of macroevolutionary conflict played out over a geological time scale.

  16. Retrovirus Entry by Endocytosis and Cathepsin Proteases

    Directory of Open Access Journals (Sweden)

    Yoshinao Kubo

    2012-01-01

    Full Text Available Retroviruses include infectious agents inducing severe diseases in humans and animals. In addition, retroviruses are widely used as tools to transfer genes of interest to target cells. Understanding the entry mechanism of retroviruses contributes to developments of novel therapeutic approaches against retrovirus-induced diseases and efficient exploitation of retroviral vectors. Entry of enveloped viruses into host cell cytoplasm is achieved by fusion between the viral envelope and host cell membranes at either the cell surface or intracellular vesicles. Many animal retroviruses enter host cells through endosomes and require endosome acidification. Ecotropic murine leukemia virus entry requires cathepsin proteases activated by the endosome acidification. CD4-dependent human immunodeficiency virus (HIV infection is thought to occur via endosomes, but endosome acidification is not necessary for the entry whereas entry of CD4-independent HIVs, which are thought to be prototypes of CD4-dependent viruses, is low pH dependent. There are several controversial results on the retroviral entry pathways. Because endocytosis and endosome acidification are complicatedly controlled by cellular mechanisms, the retrovirus entry pathways may be different in different cell lines.

  17. PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing.

    Science.gov (United States)

    Akhmetzyanova, Ilseyar; Drabczyk, Malgorzata; Neff, C Preston; Gibbert, Kathrin; Dietze, Kirsten K; Werner, Tanja; Liu, Jia; Chen, Lieping; Lang, Karl S; Palmer, Brent E; Dittmer, Ulf; Zelinskyy, Gennadiy

    2015-10-01

    Cytotoxic CD8+ T Lymphocytes (CTL) efficiently control acute virus infections but can become exhausted when a chronic infection develops. Signaling of the inhibitory receptor PD-1 is an important mechanism for the development of virus-specific CD8+ T cell dysfunction. However, it has recently been shown that during the initial phase of infection virus-specific CD8+ T cells express high levels of PD-1, but are fully competent in producing cytokines and killing virus-infected target cells. To better understand the role of the PD-1 signaling pathway in CD8+ T cell cytotoxicity during acute viral infections we analyzed the expression of the ligand on retrovirus-infected cells targeted by CTLs. We observed increased levels of PD-L1 expression after infection of cells with the murine Friend retrovirus (FV) or with HIV. In FV infected mice, virus-specific CTLs efficiently eliminated infected target cells that expressed low levels of PD-L1 or that were deficient for PD-L1 but the population of PD-L1high cells escaped elimination and formed a reservoir for chronic FV replication. Infected cells with high PD-L1 expression mediated a negative feedback on CD8+ T cells and inhibited their expansion and cytotoxic functions. These findings provide evidence for a novel immune escape mechanism during acute retroviral infection based on PD-L1 expression levels on virus infected target cells.

  18. PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing.

    Directory of Open Access Journals (Sweden)

    Ilseyar Akhmetzyanova

    2015-10-01

    Full Text Available Cytotoxic CD8+ T Lymphocytes (CTL efficiently control acute virus infections but can become exhausted when a chronic infection develops. Signaling of the inhibitory receptor PD-1 is an important mechanism for the development of virus-specific CD8+ T cell dysfunction. However, it has recently been shown that during the initial phase of infection virus-specific CD8+ T cells express high levels of PD-1, but are fully competent in producing cytokines and killing virus-infected target cells. To better understand the role of the PD-1 signaling pathway in CD8+ T cell cytotoxicity during acute viral infections we analyzed the expression of the ligand on retrovirus-infected cells targeted by CTLs. We observed increased levels of PD-L1 expression after infection of cells with the murine Friend retrovirus (FV or with HIV. In FV infected mice, virus-specific CTLs efficiently eliminated infected target cells that expressed low levels of PD-L1 or that were deficient for PD-L1 but the population of PD-L1high cells escaped elimination and formed a reservoir for chronic FV replication. Infected cells with high PD-L1 expression mediated a negative feedback on CD8+ T cells and inhibited their expansion and cytotoxic functions. These findings provide evidence for a novel immune escape mechanism during acute retroviral infection based on PD-L1 expression levels on virus infected target cells.

  19. Transcriptional Activity of Human Endogenous Retroviruses in Human Peripheral Blood Mononuclear Cells

    Directory of Open Access Journals (Sweden)

    Emanuela Balestrieri

    2015-01-01

    Full Text Available Human endogenous retroviruses (HERVs have been implicated in human physiology and in human pathology. A better knowledge of the retroviral transcriptional activity in the general population and during the life span would greatly help the debate on its pathologic potential. The transcriptional activity of four HERV families (H, K, W, and E was assessed, by qualitative and quantitative PCR, in PBMCs from 261 individuals aged from 1 to 80 years. Our results show that HERV-H, HERV-K, and HERV-W, but not HERV-E, are transcriptionally active in the test population already in the early childhood. In addition, the transcriptional levels of HERV-H, HERV-K, and HERV-W change significantly during the life span, albeit with distinct patterns. Our results, reinforce the hypothesis of a physiological correlation between HERVs activity and the different stages of life in humans. Studies aiming at identifying the factors, which are responsible for these changes during the individual’s life, are still needed. Although the observed phenomena are presumably subjected to great variability, the basal transcriptional activity of each individual, also depending on the different ages of life, must be carefully considered in all the studies involving HERVs as causative agents of disease.

  20. Immunogenicity of bivalent human papillomavirus DNA vaccine using human endogenous retrovirus envelope-coated baculoviral vectors in mice and pigs.

    Directory of Open Access Journals (Sweden)

    Hee-Jung Lee

    Full Text Available Human papillomavirus is known to be the major pathogen of cervical cancer. Here, we report the efficacy of a bivalent human papillomavirus type 16 and 18 DNA vaccine system following repeated dosing in mice and pigs using a recombinant baculovirus bearing human endogenous retrovirus envelope protein (AcHERV as a vector. The intramuscular administration of AcHERV-based HPV16L1 and HPV18L1 DNA vaccines induced antigen-specific serum IgG, vaginal IgA, and neutralizing antibodies to levels comparable to those achieved using the commercially marketed vaccine Cervarix. Similar to Cervarix, AcHERV-based bivalent vaccinations completely blocked subsequent vaginal challenge with HPV type-specific pseudovirions. However, AcHERV-based bivalent vaccinations induced significantly higher cell-mediated immune responses than Cervarix, promoting 4.5- (HPV16L1 and 3.9-(HPV18L1 fold higher interferon-γ production in splenocytes upon stimulation with antigen type-specific pseudovirions. Repeated dosing did not affect the immunogenicity of AcHERV DNA vaccines. Three sequential immunizations with AcHERV-HP18L1 DNA vaccine followed by three repeated dosing with AcHERV-HP16L1 over 11 weeks induced an initial production of anti-HPV18L1 antibody followed by subsequent induction of anti-HPV16L1 antibody. Finally, AcHERV-based bivalent DNA vaccination induced antigen-specific serum IgG immune responses in pigs. These results support the further development of AcHERV as a bivalent human papillomavirus DNA vaccine system for use in preventing the viral infection as well as treating the infected women by inducing both humoral and cell-mediated immune responses. Moreover, the possibility of repeated dosing indicates the utility of AcHERV system for reusable vectors of other viral pathogen vaccines.

  1. Immunogenicity of bivalent human papillomavirus DNA vaccine using human endogenous retrovirus envelope-coated baculoviral vectors in mice and pigs.

    Science.gov (United States)

    Lee, Hee-Jung; Hur, Yoon-Ki; Cho, Youn-Dong; Kim, Mi-Gyeong; Lee, Hoon-Taek; Oh, Yu-Kyoung; Kim, Young Bong

    2012-01-01

    Human papillomavirus is known to be the major pathogen of cervical cancer. Here, we report the efficacy of a bivalent human papillomavirus type 16 and 18 DNA vaccine system following repeated dosing in mice and pigs using a recombinant baculovirus bearing human endogenous retrovirus envelope protein (AcHERV) as a vector. The intramuscular administration of AcHERV-based HPV16L1 and HPV18L1 DNA vaccines induced antigen-specific serum IgG, vaginal IgA, and neutralizing antibodies to levels comparable to those achieved using the commercially marketed vaccine Cervarix. Similar to Cervarix, AcHERV-based bivalent vaccinations completely blocked subsequent vaginal challenge with HPV type-specific pseudovirions. However, AcHERV-based bivalent vaccinations induced significantly higher cell-mediated immune responses than Cervarix, promoting 4.5- (HPV16L1) and 3.9-(HPV18L1) fold higher interferon-γ production in splenocytes upon stimulation with antigen type-specific pseudovirions. Repeated dosing did not affect the immunogenicity of AcHERV DNA vaccines. Three sequential immunizations with AcHERV-HP18L1 DNA vaccine followed by three repeated dosing with AcHERV-HP16L1 over 11 weeks induced an initial production of anti-HPV18L1 antibody followed by subsequent induction of anti-HPV16L1 antibody. Finally, AcHERV-based bivalent DNA vaccination induced antigen-specific serum IgG immune responses in pigs. These results support the further development of AcHERV as a bivalent human papillomavirus DNA vaccine system for use in preventing the viral infection as well as treating the infected women by inducing both humoral and cell-mediated immune responses. Moreover, the possibility of repeated dosing indicates the utility of AcHERV system for reusable vectors of other viral pathogen vaccines.

  2. Friends-enemies: endogenous retroviruses are major transcriptional regulators of human DNA

    Science.gov (United States)

    Buzdin, Anton A.; Prassolov, Vladimir; Garazha, Andrew V.

    2017-06-01

    Endogenous retroviruses are mobile genetic elements hardly distinguishable from infectious, or “exogenous”, retroviruses at the time of insertion in the host DNA. Human endogenous retroviruses (HERVs) are not rare. They gave rise to multiple families of closely related mobile elements that occupy 8% of the human genome. Together, they shape genomic regulatory landscape by providing at least 320,000 human transcription factor binding sites (TFBS) located on 110,000 individual HERV elements. The HERVs host as many as 155,000 mapped DNaseI hypersensitivity sites, which denote loci active in the regulation of gene expression or chromatin structure. The contemporary view of the HERVs evolutionary dynamics suggests that at the early stages after insertion, the HERV is treated by the host cells as a foreign genetic element, and is likely to be suppressed by the targeted methylation and mutations. However, at the later stages, when significant number of mutations has been already accumulated and when the retroviral genes are broken, the regulatory potential of a HERV may be released and recruited to modify the genomic balance of transcription factor binding sites. This process goes together with further accumulation and selection of mutations, which reshape the regulatory landscape of the human DNA. However, developmental reprogramming, stress or pathological conditions like cancer, inflammation and infectious diseases, can remove the blocks limiting expression and HERV-mediated host gene regulation. This, in turn, can dramatically alter the gene expression equilibrium and shift it to a newer state, thus further amplifying instability and exacerbating the stressful situation.

  3. Lymphoma, Koala Retrovirus Infection and Reproductive Chlamydiosis in a Koala (Phascolarctos cinereus).

    Science.gov (United States)

    Fabijan, J; Woolford, L; Lathe, S; Simmons, G; Hemmatzadeh, F; Trott, D J; Speight, N

    Koala retrovirus (KoRV) infection, thought to be associated with lymphoid neoplasia, and Chlamydia pecorum-related ocular and urogenital disease are both highly prevalent in eastern Australian koala (Phascolarctos cinereus) populations. However, in South Australian koalas, little is known about KoRV infection and C. pecorum-associated disease. We report the first South Australian case of lymphoma in a KoRV-A-positive female koala also affected by severe reproductive chlamydiosis. The koala was from the Mount Lofty Ranges population and was presented with hindlimb lameness. Clinical examination identified right stifle crepitus, enlarged superficial lymph nodes and paraovarian cysts. Necropsy examination revealed extensive cartilage degeneration and loss over the medial femoral condyle, solid femoral bone marrow, mesenteric and ovarian tumours, paraovarian cysts and purulent metritis. Histopathology confirmed lymphoma in the bone marrow, mesenteric lymph nodes and ovary, with infiltration and parenchymal effacement in the pancreas, adrenal glands and other tissues. Lymphoma, KoRV and chlamydiosis are being investigated further in this population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Evidence for retrovirus infections in green turtles Chelonia mydas from the Hawaiian islands

    Science.gov (United States)

    Casey, R.N.; Quackenbush, S.L.; Work, Thierry M.; Balazs, G.H.; Bowser, P.R.; Casey, J.W.

    1997-01-01

    Apparently normal Hawaiian green turtles Chelonia mydas and those displaying fibropapillomas were analyzed for infection by retroviruses. Strikingly, all samples were positive for polymerase enhanced reverse transcriptase (PERT) with levels high enough to quantitate by the conventional reverse transcriptase (RT) assay. However, samples of skin, even from asymptomatic turtles, were RT positive, although the levels of enzyme activity in healthy turtles hatched and raised in captivity were much lower than those observed in asymptomatic free-ranging turtles. Turtles with fibropapillomas displayed a broad range of reverse transcriptase activity. Skin and eye fibropapillomas and a heart tumor were further analyzed and shown to have reverse transcriptase activity that banded in a sucrose gradient at 1.17 g ml-1. The reverse transcriptase activity purified from the heart tumor displayed a temperature optimum of 37??C and showed a preference for Mn2+ over Mg2+. Sucrose gradient fractions of this sample displaying elevated reverse transcriptase activity contained primarily retrovitalsized particles with prominent envelope spikes, when negatively stained and examined by electron microscopy. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of gradient-purified virions revealed a conserved profile among 4 independent tumors and showed 7 prominent proteins having molecular weights of 116, 83, 51, 43, 40, 20 and 14 kDa. The data suggest that retroviral infections are widespread in Hawaiian green turtles and a comprehensive investigation is warranted to address the possibility that these agents cause green turtle fibropapillomatosis (GTFP).

  5. HERVd: the Human Endogenous RetroViruses Database: update.

    Science.gov (United States)

    Paces, Jan; Pavlícek, Adam; Zika, Radek; Kapitonov, Vladimir V; Jurka, Jerzy; Paces, Václav

    2004-01-01

    An elaboration of HERVd (http://herv.img.cas.cz) is being carried out in two directions. One of them is the integration and better classification of families that diverge considerably from typical retroviral genomes. This leads to a more precise identification of members with individual families. The second improvement is better accessibility of the database and connection with human genome annotation.

  6. Electron microscope detection of an endogenous infection of retrovirus-like particles in L20B cells.

    Science.gov (United States)

    Roberts, Jason A; Thorley, Bruce R; Bruggink, Leesa D; Marshall, John A

    2013-08-01

    L20B cells are a cell line commonly used for the isolation of poliovirus. The current study indicates that L20B cells are chronically infected with a retrovirus-like particle that replicates in the cytoplasm and buds through the plasma membrane. The findings indicate that care is needed in the use of L20B cells for certain virus isolation studies and emphasize the importance of electron microscope studies as an adjunct to the development of diagnostic virology protocols.

  7. Filariae-Retrovirus Co-infection in Mice is Associated with Suppressed Virus-Specific IgG Immune Response and Higher Viral Loads.

    Science.gov (United States)

    Dietze, Kirsten Katrin; Dittmer, Ulf; Koudaimi, Daniel Karim; Schimmer, Simone; Reitz, Martina; Breloer, Minka; Hartmann, Wiebke

    2016-12-01

    Worldwide more than 2 billion people are infected with helminths, predominantly in developing countries. Co-infections with viruses such as human immunodeficiency virus (HIV) are common due to the geographical overlap of these pathogens. Helminth and viral infections induce antagonistic cytokine responses in their hosts. Helminths shift the immune system to a type 2-dominated immune response, while viral infections skew the cytokine response towards a type 1 immune response. Moreover, chronic helminth infections are often associated with a generalized suppression of the immune system leading to prolonged parasite survival, and also to a reduced defence against unrelated pathogens. To test whether helminths affect the outcome of a viral infection we set up a filarial/retrovirus co-infection model in C57BL/6 mice. Although Friend virus (FV) infection altered the L. sigmodontis-specific immunoglobulin response towards a type I associated IgG2 isotype in co-infected mice, control of L. sigmodontis infection was not affected by a FV-superinfection. However, reciprocal control of FV infection was clearly impaired by concurrent L. sigmodontis infection. Spleen weight as an indicator of pathology and viral loads in spleen, lymph nodes (LN) and bone marrow (BM) were increased in L. sigmodontis/FV-co-infected mice compared to only FV-infected mice. Numbers of FV-specific CD8+ T cells as well as cytokine production by CD4+ and CD8+ cells were alike in co-infected and FV-infected mice. Increased viral loads in co-infected mice were associated with reduced titres of neutralising FV-specific IgG2b and IgG2c antibodies. In summary our findings suggest that helminth infection interfered with the control of retroviral infection by dampening the virus-specific neutralising antibody response.

  8. Evidence for retrovirus and paramyxovirus infection of multiple bat species in china.

    Science.gov (United States)

    Yuan, Lihong; Li, Min; Li, Linmiao; Monagin, Corina; Chmura, Aleksei A; Schneider, Bradley S; Epstein, Jonathan H; Mei, Xiaolin; Shi, Zhengli; Daszak, Peter; Chen, Jinping

    2014-05-16

    Bats are recognized reservoirs for many emerging zoonotic viruses of public health importance. Identifying and cataloguing the viruses of bats is a logical approach to evaluate the range of potential zoonoses of bat origin. We characterized the fecal pathogen microbiome of both insectivorous and frugivorous bats, incorporating 281 individual bats comprising 20 common species, which were sampled in three locations of Yunnan province, by combining reverse transcription polymerase chain reaction (RT-PCR) assays and next-generation sequencing. Seven individual bats were paramyxovirus-positive by RT-PCR using degenerate primers, and these paramyxoviruses were mainly classified into three genera (Rubulavirus, Henipavirus and Jeilongvirus). Various additional novel pathogens were detected in the paramyxovirus-positive bats using Illumina sequencing. A total of 7066 assembled contigs (≥200 bp) were constructed, and 105 contigs matched eukaryotic viruses (of them 103 belong to 2 vertebrate virus families, 1 insect virus, and 1 mycovirus), 17 were parasites, and 4913 were homologous to prokaryotic microorganisms. Among the 103 vertebrate viral contigs, 79 displayed low identity (retroviruses. The present study expands our understanding of the bat virome in species commonly found in Yunnan, China, and provides insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into humans.

  9. Paleogenomic Record of the Extinction of Human Endogenous Retrovirus ERV9†

    Science.gov (United States)

    López-Sánchez, Paula; Costas, Javier C.; Naveira, Horacio F.

    2005-01-01

    An outstanding question of genome evolution is what stops the invasion of a host genome by transposable elements (TEs). The human genome, harboring the remnants of many extinct TE families, offers an extraordinary opportunity to investigate this problem. ERV9 is an endogenous retrovirus repeatedly mobilized during primate evolution, 15 to 6 million years ago (MYA), which left a trace of over a hundred provirus-like copies and at least 4,000 solitary long terminal repeats (LTRs) in the human genome. Then, its proliferation ceased for unknown reasons, and the family went extinct. We have made a detailed reconstruction of its last active subfamily, ERV9_XII, by examining 115 solitary LTRs from it. These insertions were grouped into 11 sets according to shared nucleotide variants, which could be placed in a sequential order of 10 to 6 MYA. At least 75% of the subfamily was produced 8 to 6 MYA, during a stage of intense proliferation. With new analytical tools, we show that the youngest and most prolific sets may have been produced by effectively instantaneous expansions of corresponding single-sequence variants. The extinction of this family apparently was not a consequence of its slow gradual degeneration, but the outcome of the fixation of specific restrictive alleles in the human-chimpanzee ancestral population. Three species-specific insertions (two in humans and one in chimpanzees) were identified, further supporting that extinction took place when these two species were beginning to diverge. These are the only fixed differences of this kind so far observed between humans and chimpanzees, apart from those belonging to the human endogenous retrovirus K family. PMID:15890939

  10. Paleogenomic record of the extinction of human endogenous retrovirus ERV9.

    Science.gov (United States)

    López-Sánchez, Paula; Costas, Javier C; Naveira, Horacio F

    2005-06-01

    An outstanding question of genome evolution is what stops the invasion of a host genome by transposable elements (TEs). The human genome, harboring the remnants of many extinct TE families, offers an extraordinary opportunity to investigate this problem. ERV9 is an endogenous retrovirus repeatedly mobilized during primate evolution, 15 to 6 million years ago (MYA), which left a trace of over a hundred provirus-like copies and at least 4,000 solitary long terminal repeats (LTRs) in the human genome. Then, its proliferation ceased for unknown reasons, and the family went extinct. We have made a detailed reconstruction of its last active subfamily, ERV9_XII, by examining 115 solitary LTRs from it. These insertions were grouped into 11 sets according to shared nucleotide variants, which could be placed in a sequential order of 10 to 6 MYA. At least 75% of the subfamily was produced 8 to 6 MYA, during a stage of intense proliferation. With new analytical tools, we show that the youngest and most prolific sets may have been produced by effectively instantaneous expansions of corresponding single-sequence variants. The extinction of this family apparently was not a consequence of its slow gradual degeneration, but the outcome of the fixation of specific restrictive alleles in the human-chimpanzee ancestral population. Three species-specific insertions (two in humans and one in chimpanzees) were identified, further supporting that extinction took place when these two species were beginning to diverge. These are the only fixed differences of this kind so far observed between humans and chimpanzees, apart from those belonging to the human endogenous retrovirus K family.

  11. Inactivation of AIDS-causing retroviruses by the manufacturing procedures for human plasma proteins.

    Science.gov (United States)

    Hilfenhaus, J; Gregersen, J P

    1988-04-01

    Human retroviruses causing AIDS (HIV) may occur in human plasma. Since HIV contaminated plasma cannot be completely excluded by testing for anti-HIV, AIDS safety of human plasma products can only be achieved by introducing HIV inactivating and/or eliminating methods into the manufacturing procedure. Here we review a number of methods used when manufacturing plasma derivatives at Behringwerke. These methods were previously developed either to produce a protein of required purity or to manufacture hepatitis safe products. Methods used to produce purer proteins are ethanol fractionation, pepsin treatment, affinity chromatography or various protein precipitation procedures. The method developed at Behringwerke for inactivating infectious viruses in plasma protein preparations not destroying the biological activities of the human protein is pasteurization, i.e. 10 h heat treatment of the aqueous protein solution at 60 degrees C. To investigate the HIV inactivating efficiency of the methods mentioned above, aliquots of an infectious HIV type 1 concentrate were added to a protein preparation, the resulting HIV spiked preparation treated according to the method to be studied and the amount of infectious HIV in this preparation determined before and after treatment. By all methods reported on here the HIV type 1 isolate was completely inactivated resulting in high inactivation factors. In addition, the heat stability of HIV type 2 was tested in aqueous solution at 60 degrees C proving that both HIV-1 and HIV-2 isolates are of comparably low heat stability under these conditions. From the results discussed here it can be concluded that all commercial human protein products of Behringwerke derived from either human plasma or placenta do not contain any infectious retrovirus causing AIDS and thus have a high margin of safety regarding the transmission of AIDS.

  12. Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Perron, H; Hamdani, N; Faucard, R; Lajnef, M; Jamain, S; Daban-Huard, C; Sarrazin, S; LeGuen, E; Houenou, J; Delavest, M; Moins-Teisserenc, H; Moins-Teiserenc, H; Bengoufa, D; Yolken, R; Madeira, A; Garcia-Montojo, M; Gehin, N; Burgelin, I; Ollagnier, G; Bernard, C; Dumaine, A; Henrion, A; Gombert, A; Le Dudal, K; Charron, D; Krishnamoorthy, R; Tamouza, R; Leboyer, M

    2012-12-04

    Epidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P<10-4) and in SZ (P=0.012) as compared with HC, but with higher values in BD than in SZ group (P<0.01). The corresponding DNA copy number was paradoxically lower in the genome of patients with BD (P=0.0016) or SZ (P<0.0003) than in HC. Differences in nucleotide sequence of HERV-W env were found between patients with SZ and BD as compared with HC, as well as between SZ and BD. The molecular characteristics of HERV-W env also differ from what was observed in Multiple Sclerosis (MS) and may represent distinct features of the genome of patients with BD and SZ. The seroprevalence for Toxoplasma gondii yielded low but significant association with HERV-W transcriptional level in a subgroup of BD and SZ, suggesting a potential role in particular patients. A global hypothesis of mechanisms inducing such major psychoses is discussed, placing HERV-W at the crossroads between environmental, genetic and immunological factors. Thus, particular infections would act as activators of HERV-W elements in earliest life, resulting in the production of an HERV-W envelope protein, which then stimulates pro-inflammatory and neurotoxic cascades. This hypothesis needs to be further explored as it may yield major changes in our understanding and treatment of

  13. Detection of the human endogenous retrovirus ERV3-encoded Env-protein in human tissues using antibody-based proteomics.

    Science.gov (United States)

    Fei, Chen; Atterby, Christina; Edqvist, Per-Henrik; Pontén, Fredrik; Zhang, Wei Wei; Larsson, Erik; Ryan, Frank P

    2014-01-01

    There is growing evidence to suggest that human endogenous retroviruses (HERVs) have contributed to human evolution, being expressed in development, normal physiology and disease. A key difficulty in the scientific evaluation of this potential viral contribution is the accurate demonstration of virally expressed protein in specific human cells and tissues. In this study, we have adopted the endogenous retrovirus, ERV3, as our test model in developing a reliable high-capacity methodology for the expression of such endogenous retrovirus-coded protein. Two affinity-purified polyclonal antibodies to ERV3 Env-encoded protein were generated to detect the corresponding protein expression pattern in specific human cells, tissues and organs. Sampling included normal tissues from 144 individuals ranging from childhood to old age. This included more than forty different tissues and organs and some 216 different cancer tissues representing the twenty commonest forms of human cancer. The Rudbeck Laboratory, Uppsala University and Uppsala University Hospital, Uppsala, Sweden. The potential expression at likely physiological level of the ERV3Env encoded protein in a wide range of human cells, tissues and organs. We found that ERV3 encoded Env protein is expressed at substantive levels in placenta, testis, adrenal gland, corpus luteum, Fallopian tubes, sebaceous glands, astrocytes, bronchial epithelium and the ducts of the salivary glands. Substantive expression was also seen in a variety of epithelial cells as well as cells known to undergo fusion in inflammation and in normal physiology, including fused macrophages, myocardium and striated muscle. This contrasted strongly with the low levels expressed in other tissues types. These findings suggest that this virus plays a significant role in human physiology and may also play a possible role in disease. This technique can now be extended to the study of other HERV genomes within the human chromosomes that may have contributed to

  14. (Some) cellular mechanisms influencing the transcription of human endogenous retrovirus, HERV-Fc1

    DEFF Research Database (Denmark)

    Laska, Magdalena Janina; Nissen, Kari Konstantin; Nexø, Bjørn Andersen

    2013-01-01

    DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. DNA methylation is considered an important mechanism for silencing of retroelements in the mammalian genome. However, the methylation of human endogenous retroviruses (HERVs) is not well...... and Trichostatin-A, in inducing or reactivating expression of HERV-Fc1 specific sequences and the mechanisms were investigated. In our present study, 5-aza-dC is shown to be a powerful inducer of HERV-Fc1, and at the same time it strongly inhibits methylation of DNA. Treatment with this demethylating agent 5-aza......, the results suggest that inhibition of DNA methylation/histone deacetylase can interfere with gene silencing mechanisms affecting HERV-Fc1 expression in human cells....

  15. Anti-CHMP5 single chain variable fragment antibody retrovirus infection induces programmed cell death of AML leukemic cells in vitro.

    Science.gov (United States)

    Wang, Hai-rong; Xiao, Zhen-yu; Chen, Miao; Wang, Fei-long; Liu, Jia; Zhong, Hua; Zhong, Ji-hua; Ou-Yang, Ren-rong; Shen, Yan-lin; Pan, Shu-ming

    2012-06-01

    Over-expressed CHMP5 was found to act as oncogene that probably participated in leukemogenesis. In this study, we constructed the CHMP5 single chain variable fragment antibody (CHMP5-scFv) retrovirus and studied the changes of programmed cell death (PCD) of AML leukemic cells after infection by the retrovirus. The anti-CHMP5 KC14 hybridoma cell line was constructed to generate monoclonal antibody of CHMP5. The protein expression of CHMP5 was studied using immunofluorescence analysis. pMIG-CHMP5 scFv antibody expressible retroviral vector was constructed to prepare CHMP5-scFv retrovirus. AML leukemic U937 cells were infected with the retrovirus, and programmed cell death was studied using confocal microscope, FCM and Western blot. We obtained a monoclonal antibody of CHMP5, and found the expression of CHMP5 was up-regulated in the leukemic cells. After U937 cells were infected with CHMP5-scFv retrovirus, CHMP5 protein was neutralized. Moreover, the infection resulted in a significant increase in apoptosis and necrosis of U937 cells. In U937 cells infected with CHMP5-scFv retrovirus, apoptosis-inducing factor (AIF)-mediated caspase-independent necrotic PCD was activated, but autophagic programmed cell death was not observed. Neither the intrinsic nor extrinsic apoptotic PCD pathway was activated. The granzyme B/perforin-mediated caspase-dependent apoptotic PCD pathway was not activated. CHMP5-scFv retrovirus can neutralize the abnormally high levels of the CHMP5 protein in the cytosol of AML leukemic U937 cells, thereby inducing the programmed cell death of the leukemic cells via AIF-mediated caspase-independent necrosis and apoptosis.

  16. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone.

    OpenAIRE

    Adachi, A; Gendelman, H E; Koenig, S.; Folks, T; Willey, R; Rabson, A; Martin, M. A.

    1986-01-01

    We constructed an infectious molecular clone of acquired immunodeficiency syndrome-associated retrovirus. Upon transfection, this clone directed the production of infectious virus particles in a wide variety of cells in addition to human T4 cells. The progeny, infectious virions, were synthesized in mouse, mink, monkey, and several human non-T cell lines, indicating the absence of any intracellular obstacle to viral RNA or protein production or assembly. During the course of these studies, a ...

  17. Human Endogenous Retrovirus Protein Activates Innate Immunity and Promotes Experimental Allergic Encephalomyelitis in Mice

    Science.gov (United States)

    Perron, Hervé; Dougier-Reynaud, Hei-Lanne; Lomparski, Christina; Popa, Iuliana; Firouzi, Reza; Bertrand, Jean-Baptiste; Marusic, Suzana; Portoukalian, Jacques; Jouvin-Marche, Evelyne; Villiers, Christian L.; Touraine, Jean-Louis; Marche, Patrice N.

    2013-01-01

    Multiple sclerosis (MS) is a complex multifactorial disease of the central nervous system (CNS) for which animal models have mainly addressed downstream immunopathology but not potential inducers of autoimmunity. In the absence of a pathogen known to cause neuroinflammation in MS, Mycobacterial lysate is commonly used in the form of complete Freund's adjuvant to induce autoimmunity to myelin proteins in Experimental Allergic Encephalomyelitis (EAE), an animal model for MS. The present study demonstrates that a protein from the human endogenous retrovirus HERV-W family (MSRV-Env) can be used instead of mycobacterial lysate to induce autoimmunity and EAE in mice injected with MOG, with typical anti-myelin response and CNS lesions normally seen in this model. MSRV-Env was shown to induce proinflammatory response in human macrophage cells through TLR4 activation pathway. The present results demonstrate a similar activation of murine dendritic cells and show the ability of MSRV-Env to trigger EAE in mice. In previous studies, MSRV-Env protein was reproducibly detected in MS brain lesions within microglia and perivascular macrophages. The present results are therefore likely to provide a model for MS, in which the upstream adjuvant triggering neuroinflammation is the one detected in MS active lesions. This model now allows pre-clinical studies with therapeutic agents targeting this endogenous retroviral protein in MS. PMID:24324591

  18. Human endogenous retrovirus protein activates innate immunity and promotes experimental allergic encephalomyelitis in mice.

    Directory of Open Access Journals (Sweden)

    Hervé Perron

    Full Text Available Multiple sclerosis (MS is a complex multifactorial disease of the central nervous system (CNS for which animal models have mainly addressed downstream immunopathology but not potential inducers of autoimmunity. In the absence of a pathogen known to cause neuroinflammation in MS, Mycobacterial lysate is commonly used in the form of complete Freund's adjuvant to induce autoimmunity to myelin proteins in Experimental Allergic Encephalomyelitis (EAE, an animal model for MS. The present study demonstrates that a protein from the human endogenous retrovirus HERV-W family (MSRV-Env can be used instead of mycobacterial lysate to induce autoimmunity and EAE in mice injected with MOG, with typical anti-myelin response and CNS lesions normally seen in this model. MSRV-Env was shown to induce proinflammatory response in human macrophage cells through TLR4 activation pathway. The present results demonstrate a similar activation of murine dendritic cells and show the ability of MSRV-Env to trigger EAE in mice. In previous studies, MSRV-Env protein was reproducibly detected in MS brain lesions within microglia and perivascular macrophages. The present results are therefore likely to provide a model for MS, in which the upstream adjuvant triggering neuroinflammation is the one detected in MS active lesions. This model now allows pre-clinical studies with therapeutic agents targeting this endogenous retroviral protein in MS.

  19. (Some cellular mechanisms influencing the transcription of human endogenous retrovirus, HERV-Fc1.

    Directory of Open Access Journals (Sweden)

    Magdalena Janina Laska

    Full Text Available DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. DNA methylation is considered an important mechanism for silencing of retroelements in the mammalian genome. However, the methylation of human endogenous retroviruses (HERVs is not well investigated. The aim of this study was to investigate the transcriptional potential of HERV-Fc1 proviral 5'LTR in more detail, and examined the specific influence of CpG methylation on this LTR in number of cell lines. Specifically, the role of demethylating chemicals e.g. 5-aza-2' deoxycytidine and Trichostatin-A, in inducing or reactivating expression of HERV-Fc1 specific sequences and the mechanisms were investigated. In our present study, 5-aza-dC is shown to be a powerful inducer of HERV-Fc1, and at the same time it strongly inhibits methylation of DNA. Treatment with this demethylating agent 5-aza-dC, results in significantly increased levels of HERV-Fc1 expression in cells previously not expressing HERV-Fc1, or with a very low expression level. The extent of expression of HERV-Fc1 RNAs precisely correlates with the apparent extent of demethylation of the related DNA sequences. In conclusion, the results suggest that inhibition of DNA methylation/histone deacetylase can interfere with gene silencing mechanisms affecting HERV-Fc1 expression in human cells.

  20. Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice.

    Science.gov (United States)

    Bloemker, Dominique; Mollerus, Sina; Gibbert, Kathrin; Dittmer, Ulf; Del Rey, Adriana; Schedlowski, Manfred; Engler, Harald

    2016-05-01

    Several lines of evidence indicate that the sympathetic nervous system (SNS) might be involved in the pathogenesis and progression of retroviral infections. However, experimental data are scarce and findings inconsistent. Here, we investigated the role of the SNS during acute infection with Friend virus (FV), a pathogenic murine retrovirus that causes polyclonal proliferation of erythroid precursor cells and splenomegaly in adult mice. Experimental animals were infected with FV complex, and viral load, spleen weight, and splenic noradrenaline (NA) concentration was analyzed until 25 days post infection. Results show that FV infection caused a massive but transient depletion in splenic NA during the acute phase of the disease. At the peak of the virus-induced splenomegaly, splenic NA concentration was reduced by about 90% compared to naïve uninfected mice. Concurrently, expression of the catecholamine degrading enzymes monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT) was significantly upregulated in immune cells of the spleen. Pharmacological inhibition of MAO-A and COMT by the selective inhibitors clorgyline and 3,5-dinitrocatechol, respectively, efficiently blocked NA degradation and significantly reduced viral load and virus-induced splenomegaly. In contrast, chemical sympathectomy prior to FV inoculation aggravated the acute infection and extended the duration of the disease. Together these findings demonstrate that catecholamine availability at the site of viral replication is an important factor affecting the course of retroviral infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Protective Effect of Human Endogenous Retrovirus K dUTPase Variants on Psoriasis Susceptibility

    Science.gov (United States)

    Lai, Olivia Y.; Chen, Haoyan; Michaud, Henri-Alexandre; Hayashi, Genki; Kuebler, Peter J.; Hultman, Gustaf K.; Ariza, Maria-Eugenia; Williams, Marshall V.; Batista, Mariana D.; Nixon, Douglas F.; Foerster, John; Bowcock, Anne M.; Liao, Wilson

    2012-01-01

    Previous genetic and functional studies have implicated the human endogenous retrovirus K (HERV-K) dUTPase located within the PSORS1 locus in the MHC region as a candidate psoriasis gene. Here, we describe a variant discovery and case-control association study of HERV-K dUTPase variants in 708 psoriasis cases and 349 healthy controls. Five common HERV-K dUTPase variants were found to be highly associated with psoriasis, with the strongest association occurring at the missense SNP rs3134774 (K158R, p=3.28 × 10-15, OR=2.36 [1.91-2.92]). After adjusting the association of the HERV-K dUTPase variants for the potential confounding effects of HLA alleles associated with psoriasis, the HERV-K SNPs rs9264082 and rs3134774 remained significantly associated. Haplotype analysis revealed that HERV-K haplotypes containing the non-risk alleles for rs3134774 and rs9264082 significantly reduced the risk of psoriasis. Functional testing showed higher antibody responses against recombinant HERV-K dUTPase in psoriasis patients compared to controls (pT-cell responses against a single HERV-K dUTPase peptide (ppsoriasis susceptibility, and suggest the need for additional studies to clarify the role of this dUTPase in the pathogenesis of psoriasis. PMID:22437317

  2. Human retroviruses and AIDS 1996. A compilation and analysis of nucleic acid and amino acid sequences

    Energy Technology Data Exchange (ETDEWEB)

    Myers, G.; Foley, B.; Korber, B. [eds.] [Los Alamos National Lab., NM (United States). Theoretical Div.; Mellors, J.W. [ed.] [Univ. of Pittsburgh, PA (United States); Jeang, K.T. [ed.] [National Institutes of Health, Bethesda, MD (United States). Molecular Virology Section; Wain-Hobson, S. [Pasteur Inst., Paris (France)] [ed.

    1997-04-01

    This compendium and the accompanying floppy diskettes are the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts that it comprises: (1) Nuclear Acid Alignments and Sequences; (2) Amino Acid Alignments; (3) Analysis; (4) Related Sequences; and (5) Database Communications. Information within all the parts is updated throughout the year on the Web site, http://hiv-web.lanl.gov. While this publication could take the form of a review or sequence monograph, it is not so conceived. Instead, the literature from which the database is derived has simply been summarized and some elementary computational analyses have been performed upon the data. Interpretation and commentary have been avoided insofar as possible so that the reader can form his or her own judgments concerning the complex information. In addition to the general descriptions of the parts of the compendium, the user should read the individual introductions for each part.

  3. Type W Human Endogenous Retrovirus (HERV-W) Integrations and Their Mobilization by L1 Machinery: Contribution to the Human Transcriptome and Impact on the Host Physiopathology.

    Science.gov (United States)

    Grandi, Nicole; Tramontano, Enzo

    2017-06-27

    Human Endogenous Retroviruses (HERVs) are ancient infection relics constituting ~8% of our DNA. While HERVs' genomic characterization is still ongoing, impressive amounts of data have been obtained regarding their general expression across tissues. Among HERVs, one of the most studied is the W group, which is the sole HERV group specifically mobilized by the long interspersed element-1 (LINE-1) machinery, providing a source of novel insertions by retrotransposition of HERV-W processed pseudogenes, and comprising a member encoding a functional envelope protein coopted for human placentation. The HERV-W group has been intensively investigated for its putative role in several diseases, such as cancer, inflammation, and autoimmunity. Despite major interest in the link between HERV-W expression and human pathogenesis, no conclusive correlation has been demonstrated so far. In general, (i) the absence of a proper identification of the specific HERV-W sequences expressed in a given condition, and (ii) the lack of studies attempting to connect the various observations in the same experimental conditions are the major problems preventing the definitive assessment of the HERV-W impact on human physiopathology. In this review, we summarize the current knowledge on the HERV-W group presence within the human genome and its expression in physiological tissues as well as in the main pathological contexts.

  4. Further Evidence that Human Endogenous Retrovirus K102 is a Replication Competent Foamy Virus that may Antagonize HIV-1 Replication.

    Science.gov (United States)

    Laderoute, Marian P; Larocque, Louise J; Giulivi, Antonio; Diaz-Mitoma, Francisco

    2015-01-01

    The goals of the research were to determine if a foamy effect on macrophages was due to human endogenous retrovirus K102 (HERV-K102) replication, and to further address its potential significance in HIV-1 infection. An RT-PCR HERV-K HML-2 pol method was used to screen the unknown HERV, and isolated bands were sent for sequencing. Confirmation of RNA expression was performed by a real time quantitative PCR (qPCR) pol ddCt method. Rabbit antibodies to Env peptides were used to assess expression by immunohistology and processing of Env by western blots. A qPCR pol ddCt method to ascertain genomic copy number was performed on genomic DNA isolated from plasma comparing HIV-1 exposed seronegative (HESN) commercial sex workers (CSW) to normal controls and contrasted with HIV-1 patients. HERV-K102 expression, particle production and replication were associated with foamy macrophage generation in the cultures of cord blood mononuclear cells under permissive conditions. A five-fold increased HERV-K102 pol genomic copy number was found in the HESN cohort over normal which was not found in HIV-1 positive patients (p=0.0005). This work extends the evidence that HERV-K102 has foamy virus attributes, is replication competent, and is capable of high replication rate in vivo and in vitro. This may be the first characterization of a replication-competent, foamy-like virus of humans. High particle production inferred by increased integration in the HESN cohort over HIV-1 patients raises the issue of the clinical importance of HERV-K102 particle production as an early protective innate immune response against HIV-1 replication.

  5. Characterization of the human Glvr-1 phosphate transporter/retrovirus receptor gene and promoter region.

    Science.gov (United States)

    Palmer, G; Manen, D; Bonjour, J P; Caverzasio, J

    1999-01-08

    The cell surface receptor for gibbon ape leukemia virus (Glvr-1) belongs to the type III sodium-dependent phosphate transporter/retrovirus receptor gene family. Several observations have suggested an important role for Glvr-1 in regulated Pi handling in bone forming cells and prompted us to investigate further the molecular mechanisms regulating Glvr-1 gene expression. In addition, the regulation of Glvr-1 gene expression also has potential applications to gene therapy, since retroviral vectors carrying gibbon ape leukemia virus envelope proteins are used for gene delivery into different cell types. The aim of this study was thus to clone the human Glvr-1 gene in order to describe its structure and its promoter region. Our results indicate that the Glvr-1 gene consists of 11 exons and 10 introns spread over 18kb of genomic DNA. The translation initiation site is located within exon II and the translation stop codon within exon XI. Rapid amplification of cDNA ends (5'-RACE) suggests that, in human SaOS-2 osteoblast-like cells, transcription of Glvr-1 is initiated at multiple sites, mostly located between bp 32 and 50 of the published cDNA sequence, which was initially obtained from HL-60 cells. The 5'-flanking region of the gene is characterized by a very high GC content. Reporter gene assays demonstrate the presence of a functional promoter upstream of exon I and indicate that a GC-rich region, containing two potential SP1 binding sites, is required for high promoter activity in transiently transfected SaOS-2 cells. The description of the human Glvr-1 gene structure, as well as the analysis of some structural and functional characteristics of its promoter region, provide a basis for more detailed investigation of the molecular mechanisms controlling expression of the Glvr-1 gene in bone forming cells and in other cell types.

  6. Prostate cancer progression correlates with increased humoral immune response to a human endogenous retrovirus GAG protein.

    Science.gov (United States)

    Reis, Bernardo Sgarbi; Jungbluth, Achim A; Frosina, Denise; Holz, Megan; Ritter, Erika; Nakayama, Eiichi; Ishida, Toshiaki; Obata, Yuichi; Carver, Brett; Scher, Howard; Scardino, Peter T; Slovin, Susan; Subudhi, Sumit K; Reuter, Victor E; Savage, Caroline; Allison, James P; Melamed, Jonathan; Jäger, Elke; Ritter, Gerd; Old, Lloyd J; Gnjatic, Sacha

    2013-11-15

    Human endogenous retroviruses (HERV) encode 8% of the human genome. While HERVs may play a role in autoimmune and neoplastic disease, no mechanistic association has yet been established. We studied the expression and immunogenicity of a HERV-K GAG protein encoded on chromosome 22q11.23 in relation to the clinical course of prostate cancer. In vitro expression of GAG-HERV-K was analyzed in panels of normal and malignant tissues, microarrays, and cell lines, and effects of demethylation and androgen stimulation were evaluated. Patient sera were analyzed for seroreactivity to GAG-HERV-K and other self-antigens by ELISA and seromics (protein array profiling). GAG-HERV-K expression was most frequent in prostate tissues and regulated both by demethylation of the promoter region and by androgen stimulation. Serum screening revealed that antibodies to GAG-HERV-K are found in a subset of patients with prostate cancer (33 of 483, 6.8%) but rarely in male healthy donors (1 of 55, 1.8%). Autoantibodies to GAG-HERV-K occurred more frequently in patients with advanced prostate cancer (29 of 191 in stage III-IV, 21.0%) than in early prostate cancer (4 of 292 in stages I-II, 1.4%). Presence of GAG-HERV-K serum antibody was correlated with worse survival of patients with prostate cancer, with a trend for faster biochemical recurrence in patients with antibodies to GAG-HERV-K. Preferential expression of GAG-HERV-K ch22q11.23 in prostate cancer tissue and increased frequency of autoantibodies observed in patients with advanced prostate cancer make this protein one of the first bona fide retroviral cancer antigens in humans, with potential as a biomarker for progression and biochemical recurrence rate of prostate cancer. Clin Cancer Res; 19(22); 6112-25. ©2013 AACR.

  7. Long-term absence of porcine endogenous retrovirus infection in chronically immunosuppressed patients after treatment with the porcine cell-based Academic Medical Center bioartificial liver

    NARCIS (Netherlands)

    di Nicuolo, G.; D'Alessandro, A.; Andria, B.; Scuderi, V.; Scognamiglio, M.; Tammaro, A.; Mancini, A.; Cozzolino, S.; di Florio, E.; Bracco, A.; Calise, F.; Chamuleau, R.A.F.M.

    2010-01-01

    Background: Clinical use of porcine cell-based bioartificial liver (BAL) support in acute liver failure as bridging therapy for liver transplantation exposes the patient to the risk of transmission of porcine endogenous retroviruses (PERVs) to human. This risk may be enhanced when patients receive

  8. Identification, characterization, and comparative genomic distribution of the HERV-K (HML-2 group of human endogenous retroviruses

    Directory of Open Access Journals (Sweden)

    Subramanian Ravi P

    2011-11-01

    Full Text Available Abstract Background Integration of retroviral DNA into a germ cell may lead to a provirus that is transmitted vertically to that host's offspring as an endogenous retrovirus (ERV. In humans, ERVs (HERVs comprise about 8% of the genome, the vast majority of which are truncated and/or highly mutated and no longer encode functional genes. The most recently active retroviruses that integrated into the human germ line are members of the Betaretrovirus-like HERV-K (HML-2 group, many of which contain intact open reading frames (ORFs in some or all genes, sometimes encoding functional proteins that are expressed in various tissues. Interestingly, this expression is upregulated in many tumors ranging from breast and ovarian tissues to lymphomas and melanomas, as well as schizophrenia, rheumatoid arthritis, and other disorders. Results No study to date has characterized all HML-2 elements in the genome, an essential step towards determining a possible functional role of HML-2 expression in disease. We present here the most comprehensive and accurate catalog of all full-length and partial HML-2 proviruses, as well as solo LTR elements, within the published human genome to date. Furthermore, we provide evidence for preferential maintenance of proviruses and solo LTR elements on gene-rich chromosomes of the human genome and in proximity to gene regions. Conclusions Our analysis has found and corrected several errors in the annotation of HML-2 elements in the human genome, including mislabeling of a newly identified group called HML-11. HML-elements have been implicated in a wide array of diseases, and characterization of these elements will play a fundamental role to understand the relationship between endogenous retrovirus expression and disease.

  9. Risk factors for retrovirus and hepatitis virus infections in accepted blood donors.

    Science.gov (United States)

    Custer, Brian; Kessler, Debra; Vahidnia, Farnaz; Leparc, German; Krysztof, David E; Shaz, Beth; Kamel, Hany; Glynn, Simone; Dodd, Roger Y; Stramer, Susan L

    2015-05-01

    Risk factor surveillance among infected blood donors provides information on the effectiveness of eligibility assessment and is critical for reducing risk of transfusion-transmitted infection. American Red Cross, Blood Systems, Inc., New York Blood Center, and OneBlood participated in a case-control study from 2010 to 2013. Donors with serologic and nucleic acid testing (NAT) or NAT-only confirmed human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or serology-confirmed human T-lymphotropic virus (HTLV) infections (cases) and donors with false-positive results (controls) were interviewed for putative behavioral and demographic risks. Frequencies and adjusted odds ratios (AORs) from multivariable logistic regression analyses for each exposure in cases compared to controls are reported. In the study, 196 HIV, 292 HBV, 316 HCV, and 198 HTLV cases, and 1587 controls were interviewed. For HIV, sex with an HIV+ person (AOR, 132; 95% confidence interval [CI], 27-650) and male-male sex (AOR, 62; 95% CI, 27-140) were primary risk factors. For HBV, first-time donor status (AOR, 16; 95% CI, 10-27), sex with an injection drug user (IDU; AOR, 11; 95% CI, 5-28), and black race (AOR, 11; 95% CI, 6-19) were primary. For HCV, IDU (AOR, 42; 95% CI, 13-136), first time (AOR, 18; 95% CI, 10-30), and a family member with hepatitis (AOR, 15; 95% CI, 6-40) were primary. For HTLV, sex with an IDU (AOR, 22; 95% CI, 10-48), 55 years old or more (AOR, 21; 95% CI, 8-52], and first time (AOR, 15; 95% CI, 9-24) were primary. Despite education efforts and risk screening, individuals with deferrable risks still donate; they may fail to understand or ignore or do not believe they have risk. Recipients have potential transfusion-transmitted infection risk because of nondisclosure by donors. © 2014 AABB.

  10. The Role of XMRV, a Novel Xenotropic Murine Retrovirus, in Human Prostate Cancers

    Science.gov (United States)

    2011-05-01

    expression and for subsequent release of virus particles. 293T (human embryonic kidney), 2fTGH (human fibrosarcoma ), HeLa (cervical carcinoma), and TE671...carcinoma), TE671 (human rhabdomyosarcoma), 2fTGH cells (human fibrosarcoma ), and monitored for RT release for three days post-infection. Only...cytokine. To show that XMRV is indeed restricted by IFN, we utilized a human fibrosarcoma cell line, 2fTGH, which is competent in IFN signaling. We

  11. Human endogenous retrovirus-R (ERV 3) env-like antigens ...

    African Journals Online (AJOL)

    Background: A substantial component of the vertebrate genome comprise of retrovirusrelated sequences named as endogenous retroviruses (ERVs). The role of these ERVrelated sequences in the biological processes of the host species is still unknown. However, they have been associated with tumourigenesis, ...

  12. Activation of the Long Terminal Repeat of Human Endogenous Retrovirus K by Melanoma-Specific Transcription Factor MITF-M

    Directory of Open Access Journals (Sweden)

    Iyoko Katoh

    2011-11-01

    Full Text Available The human and Old World primate genomes possess conserved endogenous retrovirus sequences that have been implicated in evolution, reproduction, and carcinogenesis. Human endogenous retrovirus (HERV-K with 5′LTR-gag-pro-pol-env-rec/np9-3′LTR sequences represents the newest retrovirus family that integrated into the human genome 1 to 5 million years ago. Although a high-level expression of HERV-K in melanomas, breast cancers, and terato-carcinomas has been demonstrated, the mechanism of the lineage-specific activation of the long terminal repeat (LTR remains obscure. We studied chromosomal HERV-K expression in MeWo melanoma cells in comparison with the basal expression in human embryonic kidney 293 (HEK293 cells. Cloned LTR of HERV-K (HML-2.HOM was also characterized by mutation and transactivation experiments. We detected multiple transcriptional initiator (Inr sites in the LTR by rapid amplification of complementary DNA ends (5′ RACE. HEK293 and MeWo showed different Inr usage. The most potent Inr was associated with a TATA box and three binding motifs of microphthalmia-associated transcription factor (MITF. Both chromosomal HERV-K expression and the cloned LTR function were strongly activated in HEK293 by transfection with MITF-M, a melanocyte/melanoma–specific isoform of MITF. Coexpression of MITF and the HERV-K core antigen was detected in retinal pigmented epithelium by an immunofluorescence analysis. Although malignant melanoma lines MeWo, G361, and SK-MEL-28 showed enhanced HERV-K transcription compared with normal melanocytes, the level of MITF-M messenger RNA persisted from normal to transformed melanocytes. Thus, MITF-M may be a prerequisite for the pigmented cell lineage–specific function of HERV-K LTR, leading to the high-level expression in malignant melanomas.

  13. The Role of XMRV, a Novel Xenotropic Murine Retrovirus, in Human Prostate Cancer

    Science.gov (United States)

    2009-05-01

    human papilloma viruses most often initiate cervical carcinomas has focused efforts on viral detection for...related virus (XMRV) was recently discovered in human prostate cancers and is the first gammaretrovirus known to infect humans . While...INTRODUCTION     Xenotropic  murine  leukemia   virus –related   virus  (XMRV)  was  recently  discovered  in   human  

  14. Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

    DEFF Research Database (Denmark)

    Christensen, Tove

    2005-01-01

    may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation...... and expression in MS are the major subjects of this review, which also proposes to synergise the herpes and HERV findings, and presents several possible pathogenic mechanisms for HERVs in MS. Copyright (c) 2005 ...

  15. Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses.

    Directory of Open Access Journals (Sweden)

    Jumpei Ito

    2017-07-01

    Full Text Available Human endogenous retroviruses (HERVs and other long terminal repeat (LTR-type retrotransposons (HERV/LTRs have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs. Overall, 794,972 HERV-TFBSs were identified. Subsequently, we identified "HERV/LTR-shared regulatory element (HSRE," defined as a TF-binding motif in HERV-TFBSs, shared within a substantial fraction of a HERV/LTR type. HSREs could be an indication that the regulatory elements of HERV/LTRs are present before their insertions. We identified 2,201 HSREs, comprising specific associations of 354 HERV/LTRs and 84 TFs. Clustering analysis showed that HERV/LTRs can be grouped according to the TF binding patterns; HERV/LTR groups bounded to pluripotent TFs (e.g., SOX2, POU5F1, and NANOG, embryonic endoderm/mesendoderm TFs (e.g., GATA4/6, SOX17, and FOXA1/2, hematopoietic TFs (e.g., SPI1 (PU1, GATA1/2, and TAL1, and CTCF were identified. Regulatory elements of HERV/LTRs tended to locate nearby and/or interact three-dimensionally with the genes involved in immune responses, indicating that the regulatory elements play an important role in controlling the immune regulatory network. Further, we demonstrated subgroup-specific TF binding within LTR7, LTR5B, and LTR5_Hs, indicating that gains or losses of the regulatory elements occurred during genomic invasions of the HERV/LTRs. Finally, we constructed dbHERV-REs, an interactive database of HERV/LTR regulatory elements (http://herv-tfbs.com/. This study provides fundamental information in understanding the impact of HERV/LTRs on host transcription, and offers insights into

  16. Low pH inactivation for xenotropic gamma retrovirus in recombinant human TNF-α receptor immunoglobulin G and mechanism of inactivation.

    Science.gov (United States)

    Ma, Rong; Cui, Xiaolan

    2014-01-01

    CHO-derived recombinant proteins for human therapeutic are used commonly. There are noninfectious endogenous retroviruses in CHO cells. Validation study for inactivation process is required. Murine xenotropic gamma retrovirus (X-MulV) is a model virus in validation study. In our previous study, optimum conditions for X-MulV inactivation were sifted. In this study, we performed a further research on low pH inactivation for evaluation of X-MulV clearance in manufacturing of recombinant human TNF-α receptor immunoglobulin G fusion proteins (rhTNF-α) for injection. Cell-based infectivity assay was used for the evaluation of X-MulV clearance. RhTNF-α were spiked with X-MulV and were inactivated at pH 3.60 ∼ 3.90, 25 ± 2 °C, and 0 ∼ 240 min, respectively. Samples incubated at the conditions for 15 ∼ 180 min were not inactivated effectively. For 4 h incubation, log10 reductions were achieved 5.0 log10. Biological activity of rhTNF-α incubated at pH 3.60, 25 °C for 4 h, which was assayed on murine L929 fibroblasts cells, was not affected by low pH. Env gene of X-MulV, which was detected by conventional PCR method for the first time, was not detected after incubation at pH 3.60, and it may be the mechanism of low pH inactivation. Copyright © 2013. Published by Elsevier Ltd.

  17. Preclinical pharmacokinetics and biodistribution of human papillomavirus DNA vaccine delivered in human endogenous retrovirus envelope-coated baculovirus vector.

    Science.gov (United States)

    Cho, Hee-Jeong; Lee, Soondong; Im, Saewon; Kim, Mi-Gyeong; Lee, Jaewoo; Lee, Hee-Jung; Lee, Keyong Ho; Kim, Sujeong; Kim, Young Bong; Oh, Yu-Kyoung

    2012-02-01

    Test pharmacokinetics and biodistribution of a human papillomavirus(HPV)16L1 DNA vaccine delivered in human endogenous retrovirus envelope protein (HERV)-expressing baculovirus (AcHERV) and those of naked plasmid vaccine. HPV16L1 gene was administrated as a naked plasmid or in AcHERV to mice via intravenous and intramuscular routes. HPV16L1 gene was extracted and assayed by quantitative real-time polymerase chain reaction, which was determined to have a detection limit of 50 copies/µg genomic DNA.. Mean residence times of HPV16L1 in AcHERV were 4.8- and 272.2-fold higher than naked HPV16L1 DNA vaccines after intramuscular and intravenous administration, respectively. Naked HPV16L1 DNA levels 1 month after injection were >3 orders of magnitude lower in each tissue tested than AcHERV-delivered HPV16L1, which was retained in most tissues without specific tissue tropism. AcHERV-delivered HPV16L1 administered intramuscularly persisted at the injection sites. However, the levels of copy numbers in muscle were low (1,800/μg genomic DNA) after 1 month, and undetectable after 6 months. HPV16L1 delivered via AcHERV resides longer in the body than HPV16L1 in naked form. The lack of tissue tropism ensures the safety of AcHERV vectors for further development.

  18. Endogenous retrovirus drives hitherto unknown proapoptotic p63 isoforms in the male germ line of humans and great apes.

    Science.gov (United States)

    Beyer, Ulrike; Moll-Rocek, Julian; Moll, Ute M; Dobbelstein, Matthias

    2011-03-01

    TAp63, but not its homolog p53, eliminates oocytes that suffered DNA damage. An equivalent gene for guarding the male germ line is currently not known. Here we identify hitherto unknown human p63 transcripts with unique 5'-ends derived from incorporated exons upstream of the currently mapped TP63 gene. These unique p63 transcripts are highly and specifically expressed in testis. Their most upstream region corresponds to a LTR of the human endogenous retrovirus 9 (ERV9). The insertion of this LTR upstream of the TP63 locus occurred only recently in evolution and is unique to humans and great apes (Hominidae). A corresponding p63 protein is the sole p63 species in healthy human testis, and is strongly expressed in spermatogenic precursors but not in mature spermatozoa. In response to DNA damage, this human male germ-cell-encoded TAp63 protein (designated GTAp63) is activated by caspase cleavage near its carboxyterminal domain and induces apoptosis. Human testicular cancer tissues and cell lines largely lost p63 expression. However, pharmacological inhibition of histone deacetylases completely restores p63 expression in testicular cancer cells (>3,000-fold increase). Our data support a model whereby testis-specific GTAp63 protects the genomic integrity of the male germ line and acts as a tumor suppressor. In Hominidae, this guardian function was greatly enhanced by integration of an endogenous retrovirus upstream of the TP63 locus that occurred 15 million years ago. By providing increased germ-line stability, this event may have contributed to the evolution of hominids and enabled their long reproductive periods.

  19. Cellular Prion Protein Combined with Galectin-3 and -6 Affects the Infectivity Titer of an Endogenous Retrovirus Assayed in Hippocampal Neuronal Cells

    OpenAIRE

    Kim, Boe-Hyun; Shin, Hae-Young; Goto, Joy J.; Carp, Richard I.; Choi, Eun-Kyoung; Kim, Yong-Sun

    2016-01-01

    Prion diseases are infectious and fatal neurodegenerative diseases which require the cellular prion protein, PrPC, for development of diseases. The current study shows that the PrPC augments infectivity and plaque formation of a mouse endogenous retrovirus, MuLV. We have established four neuronal cell lines expressing mouse PrPC, PrP+/+; two express wild type PrPC (MoPrP wild ) and the other two express mutant PrPC (MoPrP mut ). Infection of neuronal cells from various PrP+/+ and PrP-/- (MoPr...

  20. Gene-environment interactions in multiple sclerosis: innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway

    DEFF Research Database (Denmark)

    Christensen, Tove; Petersen, Thor; Thiel, Steffen

    2006-01-01

    Aspects of gene-environment interactions in multiple sclerosis (MS) were analysed in serum samples from 46 MS families (25 sporadic MS cases and 42 familial MS cases): antibodies to the MS-associated human endogenous retrovirus HERV-H, and levels of three components in the innate pathogen...

  1. Detection of human endogenous retrovirus type K-specific transcripts in testicular parenchyma and testicular germ cell tumors of adolescents and adults: clinical and biological implications

    NARCIS (Netherlands)

    H. Roelofs; R.J.H.L.M. van Gurp (Ruud); J.W. Oosterhuis (Wolter); L.H.J. Looijenga (Leendert)

    1998-01-01

    textabstractTesticular germ cell tumors (TGCTs) of adolescents and adults have been shown to contain proteins of the human endogenous retrovirus type K family. In a recent study, expression of these retroviral sequences was confirmed using in situ hybridization, which

  2. 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

  3. Alterations in Mesenteric Lymph Node T Cell Phenotype and Cytokine Secretion are Associated with Changes in Thymocyte Phenotype after LP-BM5 Retrovirus Infection

    Directory of Open Access Journals (Sweden)

    Maria C. Lopez

    2005-01-01

    Full Text Available In this study, mouse MLN cells and thymocytes from advanced stages of LP-BM5 retrovirus infection were studied. A decrease in the percentage of IL-7+ cells and an increase in the percentage of IL-16+ cells in the MLN indicated that secretion of these cytokines was also altered after LP-BM5 infection. The percentage of MLN T cells expressing IL-7 receptors was significantly reduced, while the percentage of MLN T cells expressing TNFR-p75 and of B cells expressing TNFR-p55 increased. Simultaneous analysis of surface markers and cytokine secretion was done in an attempt to understand whether the deregulation of IFN-Υ secretion could be ascribed to a defined cell phenotype, concluding that all T cell subsets studied increased IFN-Υ secretion after retrovirus infection. Finally, thymocyte phenotype was further analyzed trying to correlate changes in thymocyte phenotype with MLN cell phenotype. The results indicated that the increase in single positive either CD4+CD8- or CD4- CD8+ cells was due to accumulation of both immature (CD3- and mature (CD3+ single positive thymocytes. Moreover, single positive mature thymocytes presented a phenotype similar to the phenotype previously seen on MLN T cells. In summary, we can conclude that LP-BM5 uses the immune system to reach the thymus where it interferes with the generation of functionally mature T cells, favoring the development of T cells with an abnormal phenotype. These new T cells are activated to secrete several cytokines that in turn will favor retrovirus replication and inhibit any attempt of the immune system to control infection.

  4. [Preparation of green fluorescent protein retrovirus and its application in mediating gene transfer into retinal pigment epithelial cells].

    Science.gov (United States)

    Huang, Q; Xu, P; Liu, W; Wang, F; Gu, Q; Tian, S; Fan, Y; Xig, K; Chen, X; Li, C

    2001-07-01

    To determine whether human retinal pigment epithelial (RPE) cells can be infected by retrovirus and modified by retrovirus-mediated gene transfer. Recombination retroviral vector pLNCX-GFP (green fluorescent protein, GFP) was generated by inserting 780 bp GFP cDNA fragment into the MCS site of pLNCX. pLNCX-GFP was transfected into ecotropic packaging cell line PhiX-Eco and amphotropic packaging cell line PhiX-Ampho and PA317. Retroviral titer was tested by counting GFP expression of NIH3T3 cells. Then RPE cells were infected by using GFP retrovirus-containing supernatant. GFP was expressed and retrovirus was produced upon pLNCX-GFP being transfected into packaging cell line. The GFP retrovirus was able to infect primary cultured human RPE cells and immortalized RPE cell line. The retrovirus can introduce a foreign gene into RPE cells efficiently, thereby it can be used as an important tool to deliver gene into RPE for therapy of fundus diseases.

  5. Transcription of the human and rodent SPAM1 / PH-20 genes initiates within an ancient endogenous retrovirus

    Directory of Open Access Journals (Sweden)

    Dunn Catherine A

    2005-04-01

    Full Text Available Abstract Background Sperm adhesion molecule 1 (SPAM1 is the major mammalian testicular hyaluronidase and is expressed at high levels in sperm cells. SPAM1 protein is important for penetration of the cumulus cell layer surrounding the ovum, and is also involved in zona pellucida binding and sperm intracellular signalling. A previous study had identified SPAM1 as one of the many human genes that initiate within a transposable element. Results Examination of the human, mouse and rat SPAM1 loci revealed that transcripts initiate within the pol gene of an endogenous retrovirus (ERV element. This is highly unusual, as all previously identified ERV-initiated cellular gene transcripts initiate within the viral long terminal repeat promoter. The SPAM1 locus therefore represents an example of the evolution of a promoter from protein-coding sequence. We have identified novel alternative promoter and splicing variants of human and murine SPAM1. We show that all transcript variants are expressed primarily in the testis and are predicted to encode identical proteins. Conclusion The testis-specific promoters of the human and mouse SPAM1 genes are derived from sequence that was originally part of an ERV pol gene. This represents the first known example of an ERV-derived promoter acting in a gender-specific manner.

  6. SAMHD1 host restriction factor: a link with innate immune sensing of retrovirus infection.

    Science.gov (United States)

    Sze, Alexandre; Olagnier, David; Lin, Rongtuan; van Grevenynghe, Julien; Hiscott, John

    2013-12-13

    SAMHD1 [sterile alpha motif and histidine-aspartic domain (HD) containing protein 1] is the most recent addition to a unique group of host restriction factors that limit retroviral replication at distinct stages of the viral life cycle. SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase that degrades the intracellular pool of deoxynucleoside triphosphates available during early reverse transcription. SAMHD1 activity is blocked by the Vpx accessory function present in human immunodeficiency virus type 2 and SIVsm. Mutations in SAMHD1 are associated with the autoimmune disorder Aicardi-Goutières syndrome, thus emphasizing its role in regulation of the immune response. SAMHD1 antiretroviral activity is modulated by post-translational modifications, cell-cycle-dependent functions and cytokine-mediated changes. Innate receptors that sense retroviral DNA intermediates are the focus of intense study, and recent studies have established a link among SAMHD1 restriction, innate sensing of DNA and protective immune responses. Cell-cycle-dependent regulation of SAMHD1 by phosphorylation and the increasingly broad range of viruses inhibited by SAMHD1 further emphasize the importance of these mechanisms of host restriction. This review highlights current knowledge regarding SAMHD1 regulation and its impact on innate immune signaling and retroviral restriction. © 2013.

  7. Single-Step Conversion of Cells to Retrovirus Vector Producers with Herpes Simplex Virus–Epstein-Barr Virus Hybrid Amplicons

    Science.gov (United States)

    Sena-Esteves, Miguel; Saeki, Yoshinaga; Camp, Sara M.; Chiocca, E. Antonio; Breakefield, Xandra O.

    1999-01-01

    We report here on the development and characterization of a novel herpes simplex virus type 1 (HSV-1) amplicon-based vector system which takes advantage of the host range and retention properties of HSV–Epstein-Barr virus (EBV) hybrid amplicons to efficiently convert cells to retrovirus vector producer cells after single-step transduction. The retrovirus genes gag-pol and env (GPE) and retroviral vector sequences were modified to minimize sequence overlap and cloned into an HSV-EBV hybrid amplicon. Retrovirus expression cassettes were used to generate the HSV-EBV-retrovirus hybrid vectors, HERE and HERA, which code for the ecotropic and the amphotropic envelopes, respectively. Retrovirus vector sequences encoding lacZ were cloned downstream from the GPE expression unit. Transfection of 293T/17 cells with amplicon plasmids yielded retrovirus titers between 106 and 107 transducing units/ml, while infection of the same cells with amplicon vectors generated maximum titers 1 order of magnitude lower. Retrovirus titers were dependent on the extent of transduction by amplicon vectors for the same cell line, but different cell lines displayed varying capacities to produce retrovirus vectors even at the same transduction efficiencies. Infection of human and dog primary gliomas with this system resulted in the production of retrovirus vectors for more than 1 week and the long-term retention and increase in transgene activity over time in these cell populations. Although the efficiency of this system still has to be determined in vivo, many applications are foreseeable for this approach to gene delivery. PMID:10559361

  8. Endogenous retroviruses in systemic response to stress signals.

    Science.gov (United States)

    Cho, Kiho; Lee, Young-Kwan; Greenhalgh, David G

    2008-08-01

    Infection of germline cells with retroviruses initiates permanent proviral colonization of the germline genome. The germline-integrated proviruses, called endogenous retroviruses (ERVs), are inherited to offspring in a Mendelian order and belong to the transposable element family. Endogenous retroviruses and other long terminal repeat retroelements constitute ~8% and ~10% of the human and mouse genomes, respectively. It is likely that each individual has a distinct genomic ERV profile. Recent studies have revealed that a substantial fraction of ERVs retains the coding potentials necessary for virion assembly and replication. There are several layers of potential mechanisms controlling ERV expression: intracellular transcription environment (e.g., transcription factor pool, splicing machinery, hormones), epigenetic status of the genome (e.g., proviral methylation, histone acetylation), profile of transcription regulatory elements on each ERV's promoter, and a range of stress signals (e.g., injury, infection, environment). Endogenous retroviruses may exert pathophysiologic effects by infection followed by random reintegration into the genome, by their gene products (e.g., envelope, superantigen), and by altering the expression of neighboring genes. Several studies have provided evidence that ERVs are associated with a range of pathogenic processes involving multiple sclerosis, systemic lupus erythematosus, breast cancer, and the response to burn injury. For instance, the proinflammatory properties of the human ERV-W envelope protein play a central role in demyelination of oligodendrocytes. As reviewed in this article, recent advances in ERV biology and mammalian genomics suggest that ERVs may have a profound influence on various pathogenic processes including the response to injury and infection. Understanding the roles of ERVs in the pathogenesis of injury and infection will broaden insights into the underlying mechanisms of systemic immune disorder and organ

  9. KOALA RETROVIRUS: A REVIEW.

    Science.gov (United States)

    Kinney, Matthew E; Pye, Geoffrey W

    2016-06-01

    Koala retrovirus (KoRV) is a gammaretrovirus that has been identified in both captive and free-ranging koalas ( Phascolarctos cinereus ) with variable geographic distribution in Australia. KoRV is capable of both exogenous and endogenous transmission, which provides an interesting research platform for scientists to study active retrovirus endogenization into a host genome and offers veterinary scientists an opportunity to examine the clinical consequences of KoRV infection in koalas. Causation between KoRV and frequently recognized clinical conditions associated with immune suppression and neoplasia in koalas has not been definitively established, however research continues to evaluate a potential association. Three KoRV variants, KoRV-A, KoRV-B, and KoRV-J, have been the most thoroughly described and preliminary evidence suggests KoRV variability may be fundamental in host pathogenicity. In addition to reviewing what is currently known about KoRV, this article discusses treatment, management, and future research directions.

  10. An elastic model of partial budding of retroviruses

    Science.gov (United States)

    Zhang, Rui; Nguyen, Toan

    2008-03-01

    Retroviruses are characterized by their unique infection strategy of reverse transcription, in which the genetic information flows from RNA back to DNA. The most well known representative is the human immunodeficiency virus (HIV). Unlike budding of traditional enveloped viruses, retrovirus budding happens together with the formation of spherical virus capsids at the cell membrane. Led by this unique budding mechanism, we proposed an elastic model of retrovirus budding in this work. We found that if the lipid molecules of the membrane are supplied fast enough from the cell interior, the budding always proceeds to completion. In the opposite limit, there is an optimal size of partially budded virions. The zenith angle of these partially spherical capsids, α, is given by α˜(2̂/κσ)^1/4, where κ is the bending modulus of the membrane, σ is the surface tension of the membrane, and τ characterizes the strength of capsid protein interaction. If τ is large enough such that α˜π, the budding is complete. Our model explained many features of retrovirus partial budding observed in experiments.

  11. [Mechanisms for inhibition of retrovirus replication by APOBEC3 family].

    Science.gov (United States)

    Iwatani, Yasumasa

    2011-06-01

    Human cells developed the defense systems against retrovirus infections during the evolutions. These systems include retroviral restrictions by DNA cytidine deaminases of APOBEC3 family (A, B, C, DE, F, G, and H), which are potent factors to block the viral replication by blocking reverse transcription and/or integration and by hypermutating viral cDNA. In case of HIV-1, the viral protein, Vif abrogates the APOBEC3F/G function through specific machinery of ubiquitination and proteasomal degradation. Without Vif, APOBEC3F/G are incorporated into virus particles and block reverse transcription and/or integration in a newly infected cell. Recent advances in our understanding about biochemical and structure-biological characteristics of the enzymes provide new insights to reveal more detailed molecular mechanisms for anti-retroviral activity by APOBEC3 family. Here I briefly review how APOBEC3 proteins block retrovirus replications, focusing on APOBEC3G.

  12. Expression and activation by Epstein Barr virus of human endogenous retroviruses-W in blood cells and astrocytes: inference for multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Giuseppe Mameli

    Full Text Available BACKGROUND: Proposed co-factors triggering the pathogenesis of multiple sclerosis (MS are the Epstein Barr virus (EBV, and the potentially neuropathogenic MSRV (MS-associated retrovirus and syncytin-1, of the W family of human endogenous retroviruses. METHODOLOGY/PRINCIPAL FINDINGS: In search of links, the expression of HERV-W/MSRV/syncytin-1, with/without exposure to EBV or to EBV glycoprotein350 (EBVgp350, was studied on peripheral blood mononuclear cells (PBMC from healthy volunteers and MS patients, and on astrocytes, by discriminatory env-specific RT-PCR assays, and by flow cytometry. Basal expression of HERV-W/MSRV/syncytin-1 occurs in astrocytes and in monocytes, NK, and B, but not in T cells. This uneven expression is amplified in untreated MS patients, and dramatically reduced during therapy. In astrocytes, EBVgp350 stimulates the expression of HERV-W/MSRV/syncytin-1, with requirement of the NF-κB pathway. In EBVgp350-treated PBMC, MSRVenv and syncytin-1 transcription is activated in B cells and monocytes, but not in T cells, nor in the highly expressing NK cells. The latter cells, but not the T cells, are activated by proinflammatory cytokines. CONCLUSIONS/SIGNIFICANCE: In vitro EBV activates the potentially immunopathogenic and neuropathogenic HERV-W/MSRV/syncytin-1, in cells deriving from blood and brain. In vivo, pathogenic outcomes would depend on abnormal situations, as in late EBV primary infection, that is often symptomatic, or/and in the presence of particular host genetic backgrounds. In the blood, HERV-Wenv activation might induce immunopathogenic phenomena linked to its superantigenic properties. In the brain, toxic mechanisms against oligodendrocytes could be established, inducing inflammation, demyelination and axonal damage. Local stimulation by proinflammatory cytokines and other factors might activate further HERV-Ws, contributing to the neuropathogenity. In MS pathogenesis, a possible model could include EBV as

  13. Significant differences in genotoxicity induced by retrovirus integration in human T cells and induced pluripotent stem cells.

    Science.gov (United States)

    Zheng, Weiyan; Wang, Yingjia; Chang, Tammy; Huang, He; Yee, Jiing-Kuan

    2013-04-25

    Retrovirus is frequently used in the genetic modification of mammalian cells and the establishment of induced pluripotent stem cells (iPSCs) via cell reprogramming. Vector-induced genotoxicity could induce profound effect on the physiology and function of these stem cells and their differentiated progeny. We analyzed retrovirus-induced genotoxicity in somatic cell Jurkat and two iPSC lines. In Jurkat cells, retrovirus frequently activated host gene expression and gene activation was not dependent on the distance between the integration site and the transcription start site of the host gene. In contrast, retrovirus frequently down-regulated host gene expression in iPSCs, possibly due to the action of chromatin silencing that spreads from the provirus to the nearby host gene promoter. Our data raises the issue that some of the phenotypic variability observed among iPSC clones derived from the same parental cell line may be caused by retrovirus-induced gene expression changes rather than by the reprogramming process itself. It also underscores the importance of characterizing retrovirus integration and carrying out risk assessment of iPSCs before they can be applied in basic research and clinics. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Recombinant Origin of the Retrovirus XMRV

    National Research Council Canada - National Science Library

    Tobias Paprotka; Krista A. Delviks-Frankenberry; Oya Cingöz; Anthony Martinez; Hsing-Jien Kung; Clifford G. Tepper; Wei-Shau Hu; Matthew J. Fivash; John M. Coffin; Vinay K. Pathak

    2011-01-01

    The retrovirus XMRV (xenotropic murine leukemia virus—related virus) has been detected in human prostate tumors and in blood samples from patients with chronic fatigue syndrome, but these findings have not been replicated...

  15. How Active Are Porcine Endogenous Retroviruses (PERVs?

    Directory of Open Access Journals (Sweden)

    Joachim Denner

    2016-08-01

    Full Text Available Porcine endogenous retroviruses (PERVs represent a risk factor if porcine cells, tissues, or organs were to be transplanted into human recipients to alleviate the shortage of human transplants; a procedure called xenotransplantation. In contrast to human endogenous retroviruses (HERVs, which are mostly defective and not replication-competent, PERVs are released from normal pig cells and are infectious. PERV-A and PERV-B are polytropic viruses infecting cells of several species, among them humans; whereas PERV-C is an ecotropic virus infecting only pig cells. Virus infection was shown in co-culture experiments, but also in vivo, in the pig, leading to de novo integration of proviruses in certain organs. This was shown by measurement of the copy number per cell, finding different numbers in different organs. In addition, recombinations between PERV-A and PERV-C were observed and the recombinant PERV-A/C were found to be integrated in cells of different organs, but not in the germ line of the animals. Here, the evidence for such in vivo activities of PERVs, including expression as mRNA, protein and virus particles, de novo infection and recombination, will be summarised. These activities make screening of pigs for provirus number and PERV expression level difficult, especially when only blood or ear biopsies are available for analysis. Highly sensitive methods to measure the copy number and the expression level will be required when selecting pigs with low copy number and low expression of PERV as well as when inactivating PERVs using the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated nuclease (CRISPR/Cas technology.

  16. Upregulation of Human Endogenous Retrovirus-K Is Linked to Immunity and Inflammation in Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Saito, Toshie; Miyagawa, Kazuya; Chen, Shih-Yu; Tamosiuniene, Rasa; Wang, Lingli; Sharpe, Orr; Samayoa, Erik; Harada, Daisuke; Moonen, Jan-Renier A J; Cao, Aiqin; Chen, Pin-I; Hennigs, Jan K; Gu, Mingxia; Li, Caiyun G; Leib, Ryan D; Li, Dan; Adams, Christopher M; Del Rosario, Patricia A; Bill, Matthew; Haddad, Francois; Montoya, Jose G; Robinson, William H; Fantl, Wendy J; Nolan, Garry P; Zamanian, Roham T; Nicolls, Mark R; Chiu, Charles Y; Ariza, Maria E; Rabinovitch, Marlene

    2017-11-14

    Immune dysregulation has been linked to occlusive vascular remodeling in pulmonary arterial hypertension (PAH) that is hereditary, idiopathic, or associated with other conditions. Circulating autoantibodies, lung perivascular lymphoid tissue, and elevated cytokines have been related to PAH pathogenesis but without a clear understanding of how these abnormalities are initiated, perpetuated, and connected in the progression of disease. We therefore set out to identify specific target antigens in PAH lung immune complexes as a starting point toward resolving these issues to better inform future application of immunomodulatory therapies. Lung immune complexes were isolated and PAH target antigens were identified by liquid chromatography tandem mass spectrometry, confirmed by enzyme-linked immunosorbent assay, and localized by confocal microscopy. One PAH antigen linked to immunity and inflammation was pursued and a link to PAH pathophysiology was investigated by next-generation sequencing, functional studies in cultured monocytes and endothelial cells, and hemodynamic and lung studies in a rat. SAM domain and HD domain-containing protein 1 (SAMHD1), an innate immune factor that suppresses HIV replication, was identified and confirmed as highly expressed in immune complexes from 16 hereditary and idiopathic PAH versus 12 control lungs. Elevated SAMHD1 was localized to endothelial cells, perivascular dendritic cells, and macrophages, and SAMHD1 antibodies were prevalent in tertiary lymphoid tissue. An unbiased screen using metagenomic sequencing related SAMHD1 to increased expression of human endogenous retrovirus K (HERV-K) in PAH versus control lungs (n=4). HERV-K envelope and deoxyuridine triphosphate nucleotidohydrolase mRNAs were elevated in PAH versus control lungs (n=10), and proteins were localized to macrophages. HERV-K deoxyuridine triphosphate nucleotidohydrolase induced SAMHD1 and proinflammatory cytokines (eg, interleukin 6, interleukin 1β, and tumor

  17. Improved vaccine protection against retrovirus infection after co-administration of adenoviral vectors encoding viral antigens and type I interferon subtypes

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    Groitl Peter

    2011-09-01

    Full Text Available Abstract Background Type I interferons (IFNs exhibit direct antiviral effects, but also distinct immunomodulatory properties. In this study, we analyzed type I IFN subtypes for their effect on prophylactic adenovirus-based anti-retroviral vaccination of mice against Friend retrovirus (FV or HIV. Results Mice were vaccinated with adenoviral vectors encoding FV Env and Gag proteins alone or in combination with vectors encoding IFNα1, IFNα2, IFNα4, IFNα5, IFNα6, IFNα9 or IFNβ. Only the co-administration of adenoviral vectors encoding IFNα2, IFNα4, IFNα6 and IFNα9 resulted in strongly improved immune protection of vaccinated mice from subsequent FV challenge infection with high control over FV-induced splenomegaly and reduced viral loads. The level of protection correlated with augmented virus-specific CD4+ T cell responses and enhanced antibody titers. Similar results were obtained when mice were vaccinated against HIV with adenoviral vectors encoding HIV Env and Gag-Pol in combination with various type I IFN encoding vectors. Here mainly CD4+ T cell responses were enhanced by IFNα subtypes. Conclusions Our results indicate that certain IFNα subtypes have the potential to improve the protective effect of adenovirus-based vaccines against retroviruses. This correlated with augmented virus-specific CD4+ T cell and antibody responses. Thus, co-expression of select type I IFNs may be a valuable tool for the development of anti-retroviral vaccines.

  18. Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells.

    Science.gov (United States)

    Abraham, Nader G; Quan, Shuo; Mieyal, Paul A; Yang, Liming; Burke-Wolin, Theresa; Mingone, Christopher J; Goodman, Alvin I; Nasjletti, Alberto; Wolin, Michael S

    2002-11-01

    Carbon monoxide (CO) stimulates guanylate cyclase (GC) and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels. We transfected rat-lung pulmonary endothelial cells with a retrovirus-mediated human heme oxygenase (hHO)-1 gene. Pulmonary cells that expressed hHO-1 exhibited a fourfold increase in HO activity associated with decreases in the steady-state levels of heme and cGMP without changes in soluble GC (sGC) and endothelial nitric oxide synthase (NOS) proteins or basal nitrite production. Heme elicited significant increases in CO production and intracellular cGMP levels in both pulmonary endothelial and pulmonary hHO-1-expressing cells. N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly decreased cGMP levels in heme-treated pulmonary endothelial cells but not heme-treated hHO-1-expressing cells. In the presence of exogenous heme, CO and cGMP levels in hHO-1-expressing cells exceeded the corresponding levels in pulmonary endothelial cells. Acute exposure of endothelial cells to SnCl2, which is an inducer of HO-1, increased cGMP levels, whereas chronic exposure decreased heme and cGMP levels. These results indicate that prolonged overexpression of HO-1 ultimately decreases sGC activity by limiting the availability of cellular heme. Heme activates sGC and enhances cGMP levels via a mechanism that is largely insensitive to NOS inhibition.

  19. Identification and detection of a novel human endogenous retrovirus-related gene, and structural characterization of its related elements

    Directory of Open Access Journals (Sweden)

    Qiaoyi Liang

    2009-01-01

    Full Text Available Up-regulation of human endogenous retroviruses (HERVs is associated with many diseases, including cancer. In this study, an H family HERV (HERV-H-related gene was identified and characterized. Its spliced transcript lacks protein-coding capacity and may belong to the emerging class of noncoding RNAs (ncRNAs. The 1.3-kb RNA consisting of four exons is transcribed from an Alu element upstream of a 5.0-kb structurally incomplete HERV-H element. RT-PCR and quantitative RT-PCR results indicated that expression of this HERV-related transcript was negatively associated with colon, stomach, and kidney cancers. Its expression was induced upon treatment with DNA methylation and histone deacetylation inhibitors. A BLAT search using long terminal repeats (LTRs identified 50 other LTR homogenous HERV-H elements. Further analysis of these elements revealed that all are structurally incomplete and only five exert transcriptional activity. The results presented here recommend further investigation into a potentially functional HERV-H-related ncRNA.

  20. Single residues in the surface subunits of oncogenic sheep retrovirus envelopes distinguish receptor-mediated triggering for fusion at low pH and infection

    Energy Technology Data Exchange (ETDEWEB)

    Cote, Marceline [Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4 (Canada); Zheng, Yi-Min [Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211-7310 (United States); Albritton, Lorraine M. [Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Liu, Shan-Lu, E-mail: liushan@missouri.edu [Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4 (Canada); Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211-7310 (United States)

    2011-12-20

    Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV) are two closely related oncogenic retroviruses that share the same cellular receptor yet exhibit distinct fusogenicity and infectivity. Here, we find that the low fusogenicity of ENTV envelope protein (Env) is not because of receptor binding, but lies in its intrinsic insensitivity to receptor-mediated triggering for fusion at low pH. Distinct from JSRV, shedding of ENTV surface (SU) subunit into culture medium was not enhanced by a soluble form of receptor, Hyal2 (sHyal2), and sHyal2 was unable to effectively inactivate the ENTV pseudovirions. Remarkably, replacing either of the two amino acid residues, N191 or S195, located in the ENTV SU with the corresponding JSRV residues, H191 or G195, markedly increased the Env-mediated membrane fusion activity and infection. Reciprocal amino acid substitutions also partly switched the sensitivities of ENTV and JSRV pseudovirions to sHyal2-mediated SU shedding and inactivation. While N191 is responsible for an extra N-linked glycosylation of ENTV SU relative to that of JSRV, S195 possibly forms a hydrogen bond with a surrounding amino acid residue. Molecular modeling of the pre-fusion structure of JSRV Env predicts that the segment of SU that contains H191 to G195 contacts the fusion peptide and suggests that the H191N and G195S changes seen in ENTV may stabilize its pre-fusion structure against receptor priming and therefore modulate fusion activation by Hyal2. In summary, our study reveals critical determinants in the SU subunits of JSRV and ENTV Env proteins that likely regulate their local structures and thereby differential receptor-mediated fusion activation at low pH, and these findings explain, at least in part, their distinct viral infectivity.

  1. Dermatophilus congolensis human infection.

    Science.gov (United States)

    Towersey, L; Martins, E de C; Londero, A T; Hay, R J; Soares Filho, P J; Takiya, C M; Martins, C C; Gompertz, O F

    1993-08-01

    Four cases of human dermatophilosis observed in Rio de Janeiro, Brazil, are reported. Data that suggest nail infection by Dermatophilus congolensis are presented. The clinical spectrum of the disease ranged from an asymptomatic infection to a pustular eruption. Our findings suggest that epidermal Langerhans cells play a role in the pathogenesis of the infection.

  2. Human endogenous retrovirus HERV-K(HML-2) encodes a stable signal peptide with biological properties distinct from Rec

    Science.gov (United States)

    Ruggieri, Alessia; Maldener, Esther; Sauter, Marlies; Mueller-Lantzsch, Nikolaus; Meese, Eckart; Fackler, Oliver T; Mayer, Jens

    2009-01-01

    Background The human endogenous retrovirus HERV-K(HML-2) family is associated with testicular germ cell tumors (GCT). Various HML-2 proviruses encode viral proteins such as Env and Rec. Results We describe here that HML-2 Env gives rise to a 13 kDa signal peptide (SP) that harbors a different C-terminus compared to Rec. Subsequent to guiding Env to the endoplasmatic reticulum (ER), HML-2 SP is released into the cytosol. Biochemical analysis and confocal microscopy demonstrated that similar to Rec, SP efficiently translocates to the granular component of nucleoli. Unlike Rec, SP does not shuttle between nucleus and cytoplasm. SP is less stable than Rec as it is subjected to proteasomal degradation. Moreover, SP lacks export activity towards HML-2 genomic RNA, the main function of Rec in the original viral context, and SP does not interfere with Rec's RNA export activity. Conclusion SP is a previously unrecognized HML-2 protein that, besides targeting and translocation of Env into the ER lumen, may exert biological functions distinct from Rec. HML-2 SP represents another functional similarity with the closely related Mouse Mammary Tumor Virus that encodes an Env-derived SP named p14. Our findings furthermore support the emerging concept of bioactive SPs as a conserved retroviral strategy to modulate their host cell environment, evidenced here by a "retroviral fossil". While the specific role of HML-2 SP remains to be elucidated in the context of human biology, we speculate that it may be involved in immune evasion of GCT cells or tumorigenesis. PMID:19220907

  3. Vaccination against δ-Retroviruses: The Bovine Leukemia Virus Paradigm

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    Gerónimo Gutiérrez

    2014-06-01

    Full Text Available Bovine leukemia virus (BLV and human T-lymphotropic virus type 1 (HTLV-1 are closely related d-retroviruses that induce hematological diseases. HTLV-1 infects about 15 million people worldwide, mainly in subtropical areas. HTLV-1 induces a wide spectrum of diseases (e.g., HTLV-associated myelopathy/tropical spastic paraparesis and leukemia/lymphoma (adult T-cell leukemia. Bovine leukemia virus is a major pathogen of cattle, causing important economic losses due to a reduction in production, export limitations and lymphoma-associated death. In the absence of satisfactory treatment for these diseases and besides the prevention of transmission, the best option to reduce the prevalence of d-retroviruses is vaccination. Here, we provide an overview of the different vaccination strategies in the BLV model and outline key parameters required for vaccine efficacy.

  4. SAMHD1 knockout mice: modeling retrovirus restriction in vivo.

    Science.gov (United States)

    Wu, Li

    2013-11-20

    The host dNTP hydrolase SAMHD1 acts as a viral restriction factor to inhibit the replication of several retroviruses and DNA viruses in non-cycling human immune cells. However, understanding the physiological role of mammalian SAMHD1 has been elusive due to the lack of an animal model. Two recent studies reported the generation of samhd1 knockout mouse models for investigating the restriction of HIV-1 vectors and endogenous retroviruses in vivo. Both studies suggest that SAMHD1 is important for regulating the intracellular dNTP pool and the intrinsic immunity against retroviral infection, despite different outcomes of HIV-1 vector transduction in these mouse models. Here I discuss the significance of these new findings and the future directions in studying SAMHD1-mediated retroviral restriction.

  5. APOBEC3-mediated hypermutation of retroviral vectors produced from some retrovirus packaging cell lines.

    Science.gov (United States)

    Miller, A D; Metzger, M J

    2011-05-01

    APOBEC3 proteins are packaged into retrovirus virions and can hypermutate retroviruses during reverse transcription. We found that HT-1080 human fibrosarcoma cells hypermutate retroviruses, and that the HT-1080 cell-derived FLYA13 retrovirus packaging cells also hypermutate a retrovirus vector produced using these cells. We found no hypermutation of the same vector produced by the mouse cell-derived packaging line PT67 or by human 293 cells transfected with the vector and retrovirus packaging plasmids. We expect that avoidance of vector hypermutation will be particularly important for vectors used in gene therapy, wherein mutant proteins might stimulate deleterious immune responses.

  6. Three cysteine residues of SLC52A1, a receptor for the porcine endogenous retrovirus-A (PERV-A), play a critical role in cell surface expression and infectivity.

    Science.gov (United States)

    Colon-Moran, Winston; Argaw, Takele; Wilson, Carolyn A

    2017-07-01

    Porcine endogenous retrovirus-A (PERV-A), a gammaretrovirus, infects human cells in vitro, thus raising the potential risk of cross-species transmission in xenotransplantation. Two members of the solute carrier family 52 (SLC52A1 and SLC52A2) are PERV-A receptors. Site-directed mutagenesis of the cDNA encoding SLC52A1 identified that only one of two putative glycosylation signals is occupied by glycans. In addition, we showed that glycosylation of SLC52A1 is not necessary for PERV-A receptor function. We also identified that at a minimum, three cysteine residues are sufficient for SLC52A1 cell surface expression. Mutation of cysteine at position 365 and either of the two cysteine residues in the C-terminal tail at positions 442 or 446 reduced SLC52A1 surface expression and PERV-A infection suggesting that these residues may contribute to overall structural stability and receptor function. Understanding interactions between PERV-A and its cellular receptor may provide novel strategies to prevent zoonotic infection in the setting of xenotransplantation. Published by Elsevier Inc.

  7. Potential molecular mimicry between the human endogenous retrovirus W family envelope proteins and myelin proteins in multiple sclerosis.

    Science.gov (United States)

    Ramasamy, Ranjan; Joseph, Blessy; Whittall, Trevor

    2017-03-01

    Multiple sclerosis is an autoimmune disease caused by the destruction of the myelin sheath in the central nervous system. The major target molecules for the immune response are the myelin basic protein, myelin oligodendrocyte glycoprotein and proteolipid protein but the aetiology of the disease is as yet poorly understood. The HLA Class II allele DRB1*1501 in particular as well as DRB5*0101 and the expression of human endogenous retroviral envelope proteins have been linked to multiple sclerosis but the molecular mechanisms relating these remain to be elucidated. We hypothesised that cross-reactive peptide epitopes in retroviral envelope proteins and myelin proteins that can be presented by the two Class II DR molecules may play a role in initiating multiple sclerosis. Sequence homologies between retroviral envelope and myelin proteins and in silico predictions of peptides derived from them that are able to bind to the two Class II alleles were examined to test the hypothesis. The results support the hypothesis that molecular mimicry in peptide epitopes from envelope proteins of the HERV-W family of endogenous retroviruses and myelin proteins is possible and could potentially trigger multiple sclerosis. Mimicry between syncytin-1, a HERV-W envelope protein that is expressed during placentation, and myelin proteins may also explain the higher prevalence of multiple sclerosis in women. Experiments to test the ability of the identified peptide epitopes to activate T H cells are required to confirm the present findings. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  8. Evolution and phylogeny of insect endogenous retroviruses.

    Science.gov (United States)

    Terzian, C; Pélisson, A; Bucheton, A

    2001-01-01

    The genome of invertebrates is rich in retroelements which are structurally reminiscent of the retroviruses of vertebrates. Those containing three open reading frames (ORFs), including an env-like gene, may well be considered as endogenous retroviruses. Further support to this similarity has been provided by the ability of the env-like gene of DmeGypV (the Gypsy endogenous retrovirus of Drosophila melanogaster) to promote infection of Drosophila cells by a pseudotyped vertebrate retrovirus vector. To gain insights into their evolutionary story, a sample of thirteen insect endogenous retroviruses, which represents the largest sample analysed until now, was studied by computer-assisted comparison of the translated products of their gag, pol and env genes, as well as their LTR structural features. We found that the three phylogenetic trees based respectively on Gag, Pol and Env common motifs are congruent, which suggest a monophyletic origin for these elements. We showed that most of the insect endogenous retroviruses belong to a major clade group which can be further divided into two main subgroups which also differ by the sequence of their primer binding sites (PBS). We propose to name IERV-K and IERV-S these two major subgroups of Insect Endogenous Retro Viruses (or Insect ERrantiVirus, according to the ICTV nomenclature) which respectively use Lys and Ser tRNAs to prime reverse transcription.

  9. Pathological and Evolutionary Implications of Retroviruses as Mobile Genetic Elements

    Directory of Open Access Journals (Sweden)

    Mark A. Brown

    2013-10-01

    Full Text Available Retroviruses, a form of mobile genetic elements, have important roles in disease and primate evolution. Exogenous retroviruses, such as human immunodeficiency virus (HIV, have significant pathological implications that have created a massive public health challenge in recent years. Endogenous retroviruses (ERVs, which are the primary focus of this review, can also be pathogenic, as well as being beneficial to a host in some cases. Furthermore, retroviruses may have played a key role in primate evolution that resulted in the incorporation of these elements into the human genome. Retroviruses are mobile genetic elements that have important roles in disease and primate evolution. We will further discuss the pathogenic potential of retroviruses, including their role in cancer biology, and will briefly summarize their evolutionary implications.

  10. Morphology and ultrastructure of retrovirus particles

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    Wei Zhang

    2015-08-01

    Full Text Available Retrovirus morphogenesis entails assembly of Gag proteins and the viral genome on the host plasma membrane, acquisition of the viral membrane and envelope proteins through budding, and formation of the core through the maturation process. Although in both immature and mature retroviruses, Gag and capsid proteins are organized as paracrystalline structures, the curvatures of these protein arrays are evidently not uniform within one or among all virus particles. The heterogeneity of retroviruses poses significant challenges to studying the protein contacts within the Gag and capsid lattices. This review focuses on current understanding of the molecular organization of retroviruses derived from the sub-nanometer structures of immature virus particles, helical capsid protein assemblies and soluble envelope protein complexes. These studies provide insight into the molecular elements that maintain the stability, flexibility and infectivity of virus particles. Also reviewed are morphological studies of retrovirus budding, maturation, infection and cell-cell transmission, which inform the structural transformation of the viruses and the cells during infection and viral transmission, and lead to better understanding of the interplay between the functioning viral proteins and the host cell.

  11. Morphology and ultrastructure of retrovirus particles

    Science.gov (United States)

    Zhang, Wei; Cao, Sheng; Martin, Jessica L.; Mueller, Joachim D.; Mansky, Louis M.

    2015-01-01

    Retrovirus morphogenesis entails assembly of Gag proteins and the viral genome on the host plasma membrane, acquisition of the viral membrane and envelope proteins through budding, and formation of the core through the maturation process. Although in both immature and mature retroviruses, Gag and capsid proteins are organized as paracrystalline structures, the curvatures of these protein arrays are evidently not uniform within one or among all virus particles. The heterogeneity of retroviruses poses significant challenges to studying the protein contacts within the Gag and capsid lattices. This review focuses on current understanding of the molecular organization of retroviruses derived from the sub-nanometer structures of immature virus particles, helical capsid protein assemblies and soluble envelope protein complexes. These studies provide insight into the molecular elements that maintain the stability, flexibility and infectivity of virus particles. Also reviewed are morphological studies of retrovirus budding, maturation, infection and cell-cell transmission, which inform the structural transformation of the viruses and the cells during infection and viral transmission, and lead to better understanding of the interplay between the functioning viral proteins and the host cell. PMID:26448965

  12. Anti-inflammatory and vasoprotective activity of a retroviral-derived peptide, homologous to human endogenous retroviruses: endothelial cell effects.

    Directory of Open Access Journals (Sweden)

    George J Cianciolo

    Full Text Available Malignant and inflammatory tissues sometimes express endogenous retroviruses or their proteins. A highly-conserved sequence from retroviral transmembrane (TM proteins, termed the "immunosuppressive domain (ID", is associated with inhibition of immune and inflammatory functions. An octadecapeptide (MN10021 from the ID of retroviral TM protein p15E inhibits in vitro release of pro-inflammatory cytokines and increases synthesis of anti-inflammatory IL-10. We sought to determine if MN10021 has significant in vivo effects. MN10021, prepared by solid-phase synthesis, was dimerized through a naturally-occurring, carboxy-terminal cysteine. In vivo anti-inflammatory activity was determined using a murine model of sodium periodate (NaIO(4-induced peritonitis. In vivo vasoprotective effects were determined using: (1 a carrageenan-induced model of disseminated intravascular coagulation (DIC in mice; (2 a reverse passive Arthus model in guinea pigs; and (3 vasoregulatory effects in spontaneously hypertensive rats (SHR. In vitro studies included: (1 binding/uptake of MN10021 using human monocytes, cultured fibroblasts, and vascular endothelial cells (VEC; (2 gene expression by RT-PCR of MN10021-treated VEC; and (3 apoptosis of MN10021-treated VEC exposed to staurosporine or TNF-α. One-tenth nmol MN10021 inhibits 50 percent of the inflammatory response in the mouse peritonitis model. Furthermore, 73 nmol MN10021 completely protects mice in a lethal model of carrageenan-induced DIC and inhibits vascular leak in both the mouse DIC model and a guinea pig reverse passive Arthus reaction. MN10021 binds to and is taken up in a specific manner by both human monocytes and VEC but not by cultured human fibroblasts. Surprisingly, orally-administered MN10021 lowers blood pressure in SHR rats by 10-15% within 1 h suggesting a direct or indirect effect on the vascular endothelium. MN10021 and derived octapeptides induce iNOS (inducible nitric oxide synthase mRNA in VEC

  13. Identification of an active reverse transcriptase enzyme encoded by a human endogenous HERV-K retrovirus

    NARCIS (Netherlands)

    Berkhout, B.; Jebbink, M.; Zsíros, J.

    1999-01-01

    Of the numerous endogenous retroviral elements that are present in the human genome, the abundant HERV-K family is distinct because several members are transcriptionally active and coding for biologically active proteins. A detailed phylogeny of the HERV-K family based on the partial sequence of the

  14. Gene-environment interactions in multiple sclerosis: Innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway

    DEFF Research Database (Denmark)

    Christensen, Tove; Petersen, Thor; Thiel, Steffen

    2007-01-01

    Aspects of gene-environment interactions in multiple sclerosis (MS) were analysed in serum samples from 46 MS families (25 sporadic MS cases and 42 familial MS cases): antibodies to the MS-associated human endogenous retrovirus HERV-H, and levels of three components in the innate pathogen......-associated molecular pattern recognition: mannan-binding lectin (MBL), and MASP-2 and MASP-3. For representative MS families, we also determined herpesvirus serology for HSV-1, VZV, and EBV; and tissue typed for HLA-B, and HLA DR and DQ. In MS, a significant correlation between elevated immune reactivity to HERV-H Env...

  15. Human Retroviruses and AIDS. A compilation and analysis of nucleic acid and amino acid sequences: I--II; III--V

    Energy Technology Data Exchange (ETDEWEB)

    Myers, G.; Korber, B. [eds.] [Los Alamos National Lab., NM (United States); Wain-Hobson, S. [ed.] [Laboratory of Molecular Retrovirology, Pasteur Inst.; Smith, R.F. [ed.] [Baylor Coll. of Medicine, Houston, TX (United States). Dept. of Pharmacology; Pavlakis, G.N. [ed.] [National Cancer Inst., Frederick, MD (United States). Cancer Research Facility

    1993-12-31

    This compendium and the accompanying floppy diskettes are the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts that it comprises: (I) HIV and SIV Nucleotide Sequences; (II) Amino Acid Sequences; (III) Analyses; (IV) Related Sequences; and (V) Database Communications. Information within all the parts is updated at least twice in each year, which accounts for the modes of binding and pagination in the compendium.

  16. Human endogenous retrovirus K106 (HERV-K106 was infectious after the emergence of anatomically modern humans.

    Directory of Open Access Journals (Sweden)

    Aashish R Jha

    Full Text Available HERV-K113 and HERV-K115 have been considered to be among the youngest HERVs because they are the only known full-length proviruses that are insertionally polymorphic and maintain the open reading frames of their coding genes. However, recent data suggest that HERV-K113 is at least 800,000 years old, and HERV-K115 even older. A systematic study of HERV-K HML2 members to identify HERVs that may have infected the human genome in the more recent evolutionary past is lacking. Therefore, we sought to determine how recently HERVs were exogenous and infectious by examining sequence variation in the long terminal repeat (LTR regions of all full-length HERV-K loci. We used the traditional method of inter-LTR comparison to analyze all full length HERV-Ks and determined that two insertions, HERV-K106 and HERV-K116 have no differences between their 5' and 3' LTR sequences, suggesting that these insertions were endogenized in the recent evolutionary past. Among these insertions with no sequence differences between their LTR regions, HERV-K106 had the most intact viral sequence structure. Coalescent analysis of HERV-K106 3' LTR sequences representing 51 ethnically diverse individuals suggests that HERV-K106 integrated into the human germ line approximately 150,000 years ago, after the emergence of anatomically modern humans.

  17. Jaagsiekte Sheep Retrovirus Biology and Oncogenesis

    Science.gov (United States)

    Hofacre, Andrew; Fan, Hung

    2010-01-01

    Jaagsiekte sheep retrovirus (JSRV) is the causative agent of a lung cancer in sheep known as ovine pulmonary adenocarcinoma (OPA). The disease has been identified around the world in several breeds of sheep and goats, and JSRV infection typically has a serious impact on affected flocks. In addition, studies on OPA are an excellent model for human lung carcinogenesis. A unique feature of JSRV is that its envelope (Env) protein functions as an oncogene. The JSRV Env-induced transformation or oncogenesis has been studied in a variety of cell systems and in animal models. Moreover, JSRV studies have provided insights into retroviral genomic RNA export/expression mechanisms. JSRV encodes a trans-acting factor (Rej) within the env gene necessary for the synthesis of Gag protein from unspliced viral RNA. This review summarizes research pertaining to JSRV-induced pathogenesis, Env transformation, and other aspects of JSRV biology. PMID:21994634

  18. Functional characterization of two newly identified Human Endogenous Retrovirus coding envelope genes

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    Heidmann Thierry

    2005-03-01

    Full Text Available Abstract A recent in silico search for coding sequences of retroviral origin present in the human genome has unraveled two new envelope genes that add to the 16 genes previously identified. A systematic search among the latter for a fusogenic activity had led to the identification of two bona fide genes, named syncytin-1 and syncytin-2, most probably co-opted by primate genomes for a placental function related to the formation of the syncytiotrophoblast by cell-cell fusion. Here, we show that one of the newly identified envelope gene, named envP(b, is fusogenic in an ex vivo assay, but that its expression – as quantified by real-time RT-PCR on a large panel of human tissues – is ubiquitous, albeit with a rather low value in most tissues. Conversely, the second envelope gene, named envV, discloses a placenta-specific expression, but is not fusogenic in any of the cells tested. Altogether, these results suggest that at least one of these env genes may play a role in placentation, but most probably through a process different from that of the two previously identified syncytins.

  19. Evaluation of the immunomodulatory and antiviral effects of the cytokine combination IFN-α and IL-7 in the lymphocytic choriomeningitis virus and Friend retrovirus mouse infection models.

    Science.gov (United States)

    Audigé, Annette; Hofer, Ursula; Dittmer, Ulf; van den Broek, Maries; Speck, Roberto F

    2011-10-01

    Existing therapies for chronic viral infections are still suboptimal or have considerable side effects, so new therapeutic strategies need to be developed. One option is to boost the host's immune response with cytokines. We have recently shown in an acute ex vivo HIV infection model that co-administration of interferon (IFN)-α and interleukin (IL)-7 allows us to combine the potent anti-HIV activity of IFN-α with the beneficial effects of IL-7 on T-cell survival and function. Here we evaluated the effect of combining IFN-α and IL-7 on viral replication in vivo in the chronic lymphocytic choriomeningitis virus (LCMV) and acute Friend retrovirus (FV) infection models. In the chronic LCMV model, cytokine treatment was started during the early replication phase (i.e., on day 7 post-infection [pi]). Under the experimental conditions used, exogenous IFN-α inhibited FV replication, but had no effect on viral replication in the LCMV model. There was no therapeutic benefit of IL-7 either alone or in combination with IFN-α in either of the two infection models. In the LCMV model, dose-dependent effects of the cytokine combination on T-cell phenotype/function were observed. It is possible that these effects would translate into antiviral activity in re-challenged mice. It is also possible that another type of IFN-α/β or induction of endogenous IFN-α/β alone or in combination with IL-7 would have antiviral activity in the LCMV model. Furthermore, we cannot exclude that some effect on viral titers would have been seen at later time points not investigated here (i.e., beyond day 34 pi). Finally, IFN-α/IL-7 may inhibit the replication of other viruses. Thus it might be worth testing these cytokines in other in vivo models of chronic viral infections.

  20. Fungi that Infect Humans.

    Science.gov (United States)

    Köhler, Julia R; Hube, Bernhard; Puccia, Rosana; Casadevall, Arturo; Perfect, John R

    2017-06-01

    Fungi must meet four criteria to infect humans: growth at human body temperatures, circumvention or penetration of surface barriers, lysis and absorption of tissue, and resistance to immune defenses, including elevated body temperatures. Morphogenesis between small round, detachable cells and long, connected cells is the mechanism by which fungi solve problems of locomotion around or through host barriers. Secretion of lytic enzymes, and uptake systems for the released nutrients, are necessary if a fungus is to nutritionally utilize human tissue. Last, the potent human immune system evolved in the interaction with potential fungal pathogens, so few fungi meet all four conditions for a healthy human host. Paradoxically, the advances of modern medicine have made millions of people newly susceptible to fungal infections by disrupting immune defenses. This article explores how different members of four fungal phyla use different strategies to fulfill the four criteria to infect humans: the Entomophthorales, the Mucorales, the Ascomycota, and the Basidiomycota. Unique traits confer human pathogenic potential on various important members of these phyla: pathogenic Onygenales comprising thermal dimorphs such as Histoplasma and Coccidioides; the Cryptococcus spp. that infect immunocompromised as well as healthy humans; and important pathogens of immunocompromised patients-Candida, Pneumocystis, and Aspergillus spp. Also discussed are agents of neglected tropical diseases important in global health such as mycetoma and paracoccidiomycosis and common pathogens rarely implicated in serious illness such as dermatophytes. Commensalism is considered, as well as parasitism, in shaping genomes and physiological systems of hosts and fungi during evolution.

  1. Review of the twelfth West Coast retrovirus meeting

    Directory of Open Access Journals (Sweden)

    Melar Marta

    2005-11-01

    Full Text Available Abstract Every year the Cancer Research Institute from University of California at Irvine organizes the West Coast Retrovirus Meeting where participants have a chance to discuss the latest progress in understanding the pathology of retroviruses. The 12th meeting was held at the Hyatt Regency Suites in Palm Springs, California from October 6th to October 9th 2005, with the major focus on human immunodeficiency virus (HIV pathogenesis. Philippe Gallay from The Scripps Research Institute and Thomas J. Hope from Northwestern University organized the meeting, which covered all the steps involved in the lifecycle of retroviruses with an emphasis on virus:host interactions. The trend in research appeared to be on the restriction of viral infection, both by the endogenous, cellular restriction factors, as well as by the potential antimicrobial compounds of known or unknown mechanisms. Additionally, new stories on the inevitable feedback from the host immune system were presented as well. HIV still represents a challenge that an army of motivated people has been working on for over 20 years. And yet, the field has not reached the plateau in knowledge nor enthusiasm, which was proven again in October 2005 in Palm Springs.

  2. Endogenous retrovirus sequences expressed in male mammalian ...

    African Journals Online (AJOL)

    In humans, one ERV family, human endogenous retrovirus- K (HERV-K) is abundantly expressed, and is associated with germ cell tumours, while ERV3 env is expressed in normal human testis. Conclusion: The expression of ERVs in male reproductive tissues suggests a possible role in normal and disease conditions ...

  3. Clathrin facilitates the morphogenesis of retrovirus particles.

    Directory of Open Access Journals (Sweden)

    Fengwen Zhang

    2011-06-01

    Full Text Available The morphogenesis of retroviral particles is driven by Gag and GagPol proteins that provide the major structural component and enzymatic activities required for particle assembly and maturation. In addition, a number of cellular proteins are found in retrovirus particles; some of these are important for viral replication, but many lack a known functional role. One such protein is clathrin, which is assumed to be passively incorporated into virions due to its abundance at the plasma membrane. We found that clathrin is not only exceptionally abundant in highly purified HIV-1 particles but is recruited with high specificity. In particular, the HIV-1 Pol protein was absolutely required for clathrin incorporation and point mutations in reverse transcriptase or integrase domains of Pol could abolish incorporation. Clathrin was also specifically incorporated into other retrovirus particles, including members of the lentivirus (simian immunodeficiency virus, SIVmac, gammaretrovirus (murine leukemia virus, MLV and betaretrovirus (Mason-Pfizer monkey virus, M-PMV genera. However, unlike HIV-1, these other retroviruses recruited clathrin primarily using peptide motifs in their respective Gag proteins that mimicked motifs found in cellular clathrin adaptors. Perturbation of clathrin incorporation into these retroviruses, via mutagenesis of viral proteins, siRNA based clathrin depletion or adaptor protein (AP180 induced clathrin sequestration, had a range of effects on the accuracy of particle morphogenesis. These effects varied according to which retrovirus was examined, and included Gag and/or Pol protein destabilization, inhibition of particle assembly and reduction in virion infectivity. For each retrovirus examined, clathrin incorporation appeared to be important for optimal replication. These data indicate that a number of retroviruses employ clathrin to facilitate the accurate morphogenesis of infectious particles. We propose a model in which clathrin

  4. [Infection by human cytomegalovirus].

    Science.gov (United States)

    Sanbonmatsu Gámez, Sara; Ruiz, Mercedes Pérez; Navarro Marí, José María

    2014-02-01

    Prevalence of human cytomegalovirus infection is very high worldwide. Following primary infection, the virus remains latent, being able to cause recurrences either by reinfection with a new strain or by reactivation of the replication of the latent virus. The most severe disease is seen in congenital infection and in immunosuppressed patients, in whom the virus act as an opportunistic pathogen. Serological techniques are the methods of choice in primary infection and to determine the immune status against CMV in organ donor and receptor. Although well-standardized studies are lacking, the recent commercial availability of methods that measure cellular immune response are promising to predict the risk of CMV disease in immunosuppressed individuals. Molecular assays, that have gradually been substituting viral culture and/or antigen detection, are the most widely used methods for the diagnosis and control of CMV infection. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  5. Transcriptional and functional studies of Human Endogenous Retrovirus envelope EnvP(b) and EnvV genes in human trophoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, Amandine, E-mail: amandine.vargas@voila.fr; Thiery, Maxime, E-mail: thiery.maxime@courrier.uqam.ca; Lafond, Julie, E-mail: lafond.julie@uqam.ca; Barbeau, Benoit, E-mail: barbeau.benoit@uqam.ca

    2012-03-30

    HERV (Human Endogenous Retrovirus)-encoded envelope proteins are implicated in the development of the placenta. Indeed, Syncytin-1 and -2 play a crucial role in the fusion of human trophoblasts, a key step in placentation. Other studies have identified two other HERV env proteins, namely EnvP(b) and EnvV, both expressed in the placenta. In this study, we have fully characterized both env transcripts and their expression pattern and have assessed their implication in trophoblast fusion. Through RACE analyses, standard spliced transcripts were detected, while EnvV transcripts demonstrated alternative splicing at its 3 Prime end. Promoter activity and expression of both genes were induced in forskolin-stimulated BeWo cells and in primary trophoblasts. Although we have confirmed the fusogenic activity of EnvP(b), overexpression or silencing experiments revealed no impact of this protein on trophoblast fusion. Our results demonstrate that both env genes are expressed in human trophoblasts but are not required for syncytialization.

  6. Phylogeny-Directed Search for Murine Leukemia Virus-Like Retroviruses in Vertebrate Genomes and in Patients Suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jonas Blomberg

    2011-01-01

    Full Text Available Gammaretrovirus-like sequences occur in most vertebrate genomes. Murine Leukemia Virus (MLV like retroviruses (MLLVs are a subset, which may be pathogenic and spread cross-species. Retroviruses highly similar to MLLVs (xenotropic murine retrovirus related virus (XMRV and Human Mouse retrovirus-like RetroViruses (HMRVs reported from patients suffering from prostate cancer (PC and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS raise the possibility that also humans have been infected. Structurally intact, potentially infectious MLLVs occur in the genomes of some mammals, especially mouse. Mouse MLLVs contain three major groups. One, MERV G3, contained MLVs and XMRV/HMRV. Its presence in mouse DNA, and the abundance of xenotropic MLVs in biologicals, is a source of false positivity. Theoretically, XMRV/HMRV could be one of several MLLV transspecies infections. MLLV pathobiology and diversity indicate optimal strategies for investigating XMRV/HMRV in humans and raise ethical concerns. The alternatives that XMRV/HMRV may give a hard-to-detect “stealth” infection, or that XMRV/HMRV never reached humans, have to be considered.

  7. Koala Retroviruses: Evolution and Disease Dynamics.

    Science.gov (United States)

    Xu, Wenqin; Eiden, Maribeth V

    2015-11-01

    A retroviral etiology for malignant neoplasias in koalas has long been suspected. Evidence for retroviral involvement was bolstered in 2000 by the isolation of a koala retrovirus (KoRV), now termed KoRV-A. KoRV-A is an endogenous retrovirus-a retrovirus that infects germ cells-a feature that makes it a permanent resident of the koala genome. KoRV-A lacks the genetic diversity of an exogenous retrovirus, a quality associated with the ability of a retrovirus to cause neoplasias. In 2013, a second KoRV isolate, KoRV-B, was obtained from koalas with lymphomas in the Los Angeles Zoo. Unlike KoRV-A, which is present in the genomes of all koalas in the United States, KoRV-B is restricted in its distribution and is associated with host pathology (neoplastic disease). Here, our current understanding of the evolution of endogenous and exogenous KoRVs, and the relationship between them, is reviewed to build a perspective on the future impact of these viruses on koala sustainability.

  8. Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics.

    Science.gov (United States)

    Gilroy, Kathryn L; Terry, Anne; Naseer, Asif; de Ridder, Jeroen; Allahyar, Amin; Wang, Weiwei; Carpenter, Eric; Mason, Andrew; Wong, Gane K-S; Cameron, Ewan R; Kilbey, Anna; Neil, James C

    2016-01-01

    Retroviruses have been foundational in cancer research since early studies identified proto-oncogenes as targets for insertional mutagenesis. Integration of murine gamma-retroviruses into the host genome favours promoters and enhancers and entails interaction of viral integrase with host BET/bromodomain factors. We report that this integration pattern is conserved in feline leukaemia virus (FeLV), a gamma-retrovirus that infects many human cell types. Analysis of FeLV insertion sites in the MCF-7 mammary carcinoma cell line revealed strong bias towards active chromatin marks with no evidence of significant post-integration growth selection. The most prominent FeLV integration targets had little overlap with the most abundantly expressed transcripts, but were strongly enriched for annotated cancer genes. A meta-analysis based on several gamma-retrovirus integration profiling (GRIP) studies in human cells (CD34+, K562, HepG2) revealed a similar cancer gene bias but also remarkable cell-type specificity, with prominent exceptions including a universal integration hotspot at the long non-coding RNA MALAT1. Comparison of GRIP targets with databases of super-enhancers from the same cell lines showed that these have only limited overlap and that GRIP provides unique insights into the upstream drivers of cell growth. These observations elucidate the oncogenic potency of the gamma-retroviruses and support the wider application of GRIP to identify the genes and growth regulatory circuits that drive distinct cancer types.

  9. Human leukemia antigen-A*0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses.

    Science.gov (United States)

    Tu, Xiaoning; Li, Shan; Zhao, Lijuan; Xiao, Ran; Wang, Xiuling; Zhu, Fan

    2017-08-01

    Human endogenous retrovirus W family (HERV-W) envelope (env) has been reported to be related to several human diseases, including autoimmune disorders, and it could activate innate immunity. However, there are no reports investigating whether human leukemia antigen (HLA)-A*0201(+) restriction is involved in the immune response caused by HERV-W env in neuropsychiatric diseases. In the present study, HERV-W env-derived epitopes presented by HLA-A*0201 are described with the potential for use in adoptive immunotherapy. Five peptides displaying HLA-A*0201-binding motifs were predicted using SYFEPITHI and BIMAS, and synthesized. A CCK-8 assay showed peptides W, Q and T promoted lymphocyte proliferation. Stimulation of peripheral blood mononuclear cells from HLA-A*0201(+) donors with each of these peptides induced peptide-specific CD8(+) T cells. High numbers of IFN-γ-secreting T cells were also detectable after several weekly stimulations with W, Q and T. Besides lysis of HERV-W env-loaded target cells, specific apoptosis was also observed. These data demonstrate that human T cells can be sensitized toward HERV-W env peptides (W, Q and T) and, moreover, pose a high killing potential toward HERV-W env-expressing U251 cells. In conclusion, peptides W Q and T, which are HERV-W env antigenic epitopes, have both antigenicity and immunogenicity, and can cause strong T cell immune responses. Our data strengthen the view that HERV-W env should be considered as an autoantigen that can induce autoimmunity in neuropsychiatric diseases, such as multiple sclerosis and schizophrenia. These data might provide an experimental foundation for a HERV-W env peptide vaccine and new insight into the treatment of neuropsychiatric diseases.

  10. Endogenous Retroviruses: With Us and Against Us

    Science.gov (United States)

    Meyer, Thomas J.; Rosenkrantz, Jimi L.; Carbone, Lucia; Chavez, Shawn L.

    2017-04-01

    Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci. In some cases, old copies are removed via recombination and other mechanisms. This creates a shifting landscape of ERV copies within host genomes. New insertions can disrupt normal expression of nearby genes via directly inserting into key regulatory elements or by containing regulatory motifs within their sequences. Further, the transcriptional silencing of ERVs via epigenetic modification may result in changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can be potent sources of regulatory disruption as well as genetic innovation. Here, we provide a brief review of the association between ERVs and gene expression, especially as observed in pre-implantation development and placentation. Moreover, we will describe the roles ERVs may play in somatic tissues, mostly in the context of human disease, including cancer, neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent discovery that some ERVs may have been pressed into the service of their host genomes to aid in the innate immune response to exogenous viral infections.

  11. Expanded Regulatory T Cells in Chronically Friend Retrovirus-Infected Mice Suppress Immunity to a Murine Cytomegalovirus Superinfection

    OpenAIRE

    Duppach, Janine; Francois, Sandra; Jara J Joedicke; Dittmer, Ulf; Kraft, Anke R. M.

    2014-01-01

    It is still unclear whether expanded and activated regulatory T cells (Tregs) in chronic viral infections can influence primary immune responses against superinfections with unrelated viruses. Expanded Tregs found in the spleens of chronically Friend virus (FV)-infected mice decreased murine cytomegalovirus (mCMV)-specific CD8+ T cell responses during acute mCMV superinfection. This suppression of mCMV-specific T cell immunity was found only in organs with FV-induced Treg expansion. Surprisin...

  12. Endogenous Retroviruses in Domestic Animals

    Science.gov (United States)

    Garcia-Etxebarria, Koldo; Sistiaga-Poveda, Maialen; Jugo, Begoña Marina

    2014-01-01

    Endogenous retroviruses (ERVs) are genomic elements that are present in a wide range of vertebrates. Although the study of ERVs has been carried out mainly in humans and model organisms, recently, domestic animals have become important, and some species have begun to be analyzed to gain further insight into ERVs. Due to the availability of complete genomes and the development of new computer tools, ERVs can now be analyzed from a genome-wide viewpoint. In addition, more experimental work is being carried out to analyze the distribution, expression and interplay of ERVs within a host genome. Cats, cattle, chicken, dogs, horses, pigs and sheep have been scrutinized in this manner, all of which are interesting species in health and economic terms. Furthermore, several studies have noted differences in the number of endogenous retroviruses and in the variability of these elements among different breeds, as well as their expression in different tissues and the effects of their locations, which, in some cases, are near genes. These findings suggest a complex, intriguing relationship between ERVs and host genomes. In this review, we summarize the most important in silico and experimental findings, discuss their implications and attempt to predict future directions for the study of these genomic elements. PMID:25132796

  13. Characterisation of a Novel Retrovirus and a dsDNA Virus Infecting the Coral Algal Endosymbiont, Symbiodinium sp.

    Science.gov (United States)

    Weynberg, K. D.; Neave, M. J.; Clode, P. L.; Voolstra, C. R.; Brownlee, C.; Laffy, P.; Webster, N.; Levin, R.; Wood-Charlson, E.; van Oppen, M. J.

    2016-02-01

    Research into viruses associated with coral reefs is a newly emerging field. Corals form an important symbiotic relationship with the dinoflagellate species Symbiodinium, which the coral relies heavily upon for nutrients and calcification. Coral bleaching is the result of disruption of this symbiosis when the algae and/or its photosynthetic pigments are lost from the coral tissues. Environmental stressors, including elevated sea surface temperatures and increased UV light exposure, have been implicated in coral bleaching. We set out to test the hypothesis that Symbiodinium in culture plays host to a latent virus that switches to a lytic infection under stress, such as UV exposure or elevated temperature. Analysis of Symbiodinium cultures (isolated from corals on the Great Barrier Reef) using flow cytometry and transmission electron microscopy (TEM), revealed an active viral infection was ongoing, regardless of experimental conditions. Morphological analysis using TEM revealed filamentous and icosahedral virus-like particles associated with Symbiodinium cultures. We present genomic data of the virus assemblages isolated from cultured Symbiodinium cells that indicate this dinoflagellate is targeted by both a dsDNA virus, related to members of the Nucleo-Cytoplasmic Large dsDNA Virus family (NCLDV), and a novel ssRNA virus related to the Orthoretrovirinae. Further investigations are underway to detect viruses in freshly isolated Symbiodinium from reef corals and to compare these with viruses observed in laboratory cultures of this symbiotic alga. We aim to develop molecular diagnostic probes to detect viruses in field samples to help monitor and assess the impact of viruses in coral bleaching and other climate change-related events, which have huge implications for the health of coral reefs to future global climate scenarios.

  14. Retrovirus maturation-an extraordinary structural transformation.

    Science.gov (United States)

    Mattei, Simone; Schur, Florian Km; Briggs, John Ag

    2016-06-01

    Retroviruses such as HIV-1 assemble and bud from infected cells in an immature, non-infectious form. Subsequently, a series of proteolytic cleavages catalysed by the viral protease leads to a spectacular structural rearrangement of the viral particle into a mature form that is competent to fuse with and infect a new cell. Maturation involves changes in the structures of protein domains, in the interactions between protein domains, and in the architecture of the viral components that are assembled by the proteins. Tight control of proteolytic cleavages at different sites is required for successful maturation, and the process is a major target of antiretroviral drugs. Here we will describe what is known about the structures of immature and mature retrovirus particles, and about the maturation process by which one transitions into the other. Despite a wealth of available data, fundamental questions about retroviral maturation remain unanswered. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. A novel recombinant retrovirus in the genomes of modern birds combines features of avian and mammalian retroviruses.

    Science.gov (United States)

    Henzy, Jamie E; Gifford, Robert J; Johnson, Welkin E; Coffin, John M

    2014-03-01

    Endogenous retroviruses (ERVs) represent ancestral sequences of modern retroviruses or their extinct relatives. The majority of ERVs cluster alongside exogenous retroviruses into two main groups based on phylogenetic analyses of the reverse transcriptase (RT) enzyme. Class I includes gammaretroviruses, and class II includes lentiviruses and alpha-, beta-, and deltaretroviruses. However, analyses of the transmembrane subunit (TM) of the envelope glycoprotein (env) gene result in a different topology for some retroviruses, suggesting recombination events in which heterologous env sequences have been acquired. We previously demonstrated that the TM sequences of five of the six genera of orthoretroviruses can be divided into three types, each of which infects a distinct set of vertebrate classes. Moreover, these classes do not always overlap the host range of the associated RT classes. Thus, recombination resulting in acquisition of a heterologous env gene could in theory facilitate cross-species transmissions across vertebrate classes, for example, from mammals to reptiles. Here we characterized a family of class II avian ERVs, "TgERV-F," that acquired a mammalian gammaretroviral env sequence. Although TgERV-F clusters near a sister clade to alpharetroviruses, its genome also has some features of betaretroviruses. We offer evidence that this unusual recombinant has circulated among several avian orders and may still have infectious members. In addition to documenting the infection of a nongalliform avian species by a mammalian retrovirus, TgERV-F also underscores the importance of env sequences in reconstructing phylogenies and supports a possible role for env swapping in allowing cross-species transmissions across wide taxonomic distances. Retroviruses can sometimes acquire an envelope gene (env) from a distantly related retrovirus. Since env is a key determinant of host range, such an event affects the host range of the recombinant virus and can lead to the creation

  16. Initial preclinical safety of non-replicating human endogenous retrovirus envelope protein-coated baculovirus vector-based vaccines against human papillomavirus.

    Science.gov (United States)

    Han, Su-Eun; Kim, Mi-Gyeong; Lee, Soondong; Cho, Hee-Jeong; Byun, Youngro; Kim, Sujeong; Kim, Young Bong; Choi, Yongseok; Oh, Yu-Kyoung

    2013-12-01

    Human endogenous retrovirus (HERV) envelope protein-coated, baculovirus vector-based HPV 16 L1 (AcHERV-HPV16L1) is a non-replicating recombinant baculoviral vaccine. Here, we report an initial evaluation of the preclinical safety of AcHERV-HPV16L1 vaccine. In an acute toxicity study, a single administration of AcHERV-HPV16L1 DNA vaccine given intramuscularly (i.m.) to mice at a dose of 1 × 10(8) plaque-forming units (PFU) did not cause significant changes in body weight compared with vehicle-treated controls. It did cause a brief increase in the weights of some organs on day 15 post-treatment, but by day 30, all organ weights were not significantly different from those in the vehicle-treated control group. No hematological changes were observed on day 30 post-treatment. In a range-finding toxicity study with three doses of 1 × 10(7) , 2 × 10(7) and 5 × 10(7) PFU once daily for 5 days, the group treated with 5 × 10(7) PFU showed a transient decrease in the body weights from day 5 to day 15 post-treatment, but recovery to the levels similar to those in the vehicle-treated control group by post-treatment day 20. Organ weights were slightly higher for lymph nodes, spleen, thymus and liver after repeated dosing with 5 × 10(7) PFU on day 15, but had normalized by day 30. Moreover, repeated administration of AcHERV-HPV16L1 did not induce myosin-specific autoantibody in serum, and did not cause immune complex deposition or tissue damage at injection sites. Taken together, these results provide preliminary evidence of the preclinical safety of AcHERV-based HPV16L1 DNA vaccines in mice. Copyright © 2012 John Wiley & Sons, Ltd.

  17. Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase.

    Science.gov (United States)

    Xiao, Ran; Li, Shan; Cao, Qian; Wang, Xiuling; Yan, Qiujin; Tu, Xiaoning; Zhu, Ying; Zhu, Fan

    2017-06-01

    Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

  18. Inhibition of budding/release of porcine endogenous retrovirus.

    Science.gov (United States)

    Abe, Masumi; Fukuma, Aiko; Yoshikawa, Rokusuke; Miyazawa, Takayuki; Yasuda, Jiro

    2014-08-01

    PERV is integrated into the genome of all pigs. PERV-A and PERV-B are polytropic and can productively infect human cell lines, whereas PERV-C is ecotropic. Recombinant PERV-A/C can infect human cells and exhibits high titer replication. Therefore, use of pigs for human xenotransplantation raises concerns about the risks of transfer of this infectious agent from donors to xenotransplantation recipients. To establish strategies to inhibit PERV production from cells, in the present study, we investigated the mechanism of PERV budding and anti-PERV activity of Tetherin/BST-2. The results showed that DN mutants of WWP-2, Tsg101, and Vps4A/B markedly reduced PERV production in human and porcine cell lines, suggesting that PERV budding uses these cellular factors and the cellular MVB sorting pathway as well as many other retroviruses. Moreover, PERV production was also reduced by human and porcine Tetherin/BST-2. These data are useful for developing strategies to inhibit PERV production and may reduce the risk of PERV infection in xenotransplantation. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  19. Immunising with the transmembrane envelope proteins of different retroviruses including HIV-1

    Science.gov (United States)

    Denner, Joachim

    2013-01-01

    The induction of neutralizing antibodies is a promising way to prevent retrovirus infections. Neutralizing antibodies are mainly directed against the envelope proteins, which consist of two molecules, the surface envelope (SU) protein and the transmembrane envelope (TM) protein. Antibodies broadly neutralizing the human immunodeficiencvy virus-1 (HIV-1) and binding to the TM protein gp41 of the virus have been isolated from infected individuals. Their epitopes are located in the membrane proximal external region (MPER). Since there are difficulties to induce such neutralizing antibodies as basis for an effective AIDS vaccine, we performed a comparative analysis immunising with the TM proteins of different viruses from the family Retroviridae. Both subfamilies, the Orthoretrovirinae and the Spumaretrovirinae were included. In this study, the TM proteins of three gammaretroviruses including (1) the porcine endogenous retrovirus (PERV), (2) the Koala retrovirus (KoRV), (3) the feline leukemia virus (FeLV), of two lentiviruses, HIV-1, HIV-2, and of two spumaviruses, the feline foamy virus (FFV) and the primate foamy virus (PFV) were used for immunisation. Whereas in all immunisation studies binding antibodies were induced, neutralizing antibodies were only found in the case of the gammaretroviruses. The induced antibodies were directed against the MPER and the fusion peptide proximal region (FPPR) of their TM proteins; however only the antibodies against the MPER were neutralizing. Most importantly, the epitopes in the MPER were localized in the same position as the epitopes of the antibodies broadly neutralizing HIV-1 in the TM protein gp41 of HIV-1, indicating that the MPER is an effective target for the neutralization of retroviruses. PMID:23249763

  20. [Listeria monocytogenes in human infections].

    Science.gov (United States)

    Kołakowska, Agnieszka; Madajczak, Grzegorz

    2011-01-01

    The Listeria genus is distinguished into six species from which just one--Listeria monocytogenes is pathogenic for humans. The main route of acquisition of Listeria is through the ingestion of contaminated food products. An important element of the L. monocytogenes pathogenesis infection is affiliation with high-risk group of immunocompromised patients, infants or pregnant women, who infected by this microorganism can lead to miscarriage. Listeriosis can appear in the form of sepsis, infection of the nervous system or local abscesses. Another form of listeriosis is gastrointestinal tract infection--noticed in case of food poisoning outbreak.

  1. Novel Denisovan and Neanderthal retroviruses

    National Research Council Canada - National Science Library

    Lee, Adam; Huntley, Derek; Aiewsakun, Pakorn; Kanda, Ravinder K; Lynn, Claire; Tristem, Michael

    2014-01-01

    Following the recent availability of high-coverage genomes for Denisovan and Neanderthal hominids, we conducted a screen for endogenized retroviruses, identifying six novel, previously unreported HERV-K(HML2) elements...

  2. Targeting Persistent Human Papillomavirus Infection.

    Science.gov (United States)

    Shanmugasundaram, Srinidhi; You, Jianxin

    2017-08-18

    While the majority of Human papillomavirus (HPV) infections are transient and cleared within a couple of years following exposure, 10-20% of infections persist latently, leading to disease progression and, ultimately, various forms of invasive cancer. Despite the clinical efficiency of recently developed multivalent prophylactic HPV vaccines, these preventive measures are not effective against pre-existing infection. Additionally, considering that the burden associated with HPV is greatest in regions with limited access to preventative vaccination, the development of effective therapies targeting persistent infection remains imperative. This review discusses not only the mechanisms underlying persistent HPV infection, but also the promise of immunomodulatory therapeutic vaccines and small-molecular inhibitors, which aim to augment the host immune response against the viral infection as well as obstruct critical viral-host interactions.

  3. Restriction genes for retroviruses influence the risk of multiple sclerosis

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Hansen, Bettina; Nissen, Kari K

    2013-01-01

    known for a long time. Today human restriction genes for retroviruses include amongst others TRIMs, APOBEC3s, BST2 and TREXs. We have therefore looked for a role of these retroviral restriction genes in MS using genetic epidemiology. We here report that markers in two TRIMs, TRIM5 and TRIM22......We recently described that the autoimmune, central nervous system disease, multiple sclerosis (MS), is genetically associated with the human endogenous retroviral locus, HERV-Fc1, in Scandinavians. A number of dominant human genes encoding factors that restrict retrovirus replication have been...

  4. An N-terminally truncated envelope protein encoded by a human endogenous retrovirus W locus on chromosome Xq22.3

    Directory of Open Access Journals (Sweden)

    Roebke Christina

    2010-08-01

    Full Text Available Abstract Background We previously showed that the envelope (env sequence of a human endogenous retrovirus (HERV-W locus on chromosome Xq22.3 is transcribed in human peripheral blood mononuclear cells. The env open reading frame (ORF of this locus is interrupted by a premature stop at codon 39, but otherwise harbors a long ORF for an N-terminally truncated 475 amino acid Env protein, starting at an in-frame ATG at codon 68. We set out to characterize the protein encoded by that ORF. Results Transient expression of the 475 amino acid Xq22.3 HERV-W env ORF produced an N-terminally truncated HERV-W Env protein, as detected by the monoclonal anti-HERV-W Env antibodies 6A2B2 and 13H5A5. Remarkably, reversion of the stop at codon 39 in Xq22.3 HERV-W env reconstituted a full-length HERV-W Xq22.3 Env protein. Similar to the full-length HERV-W Env protein Syncytin-1, reconstituted full-length Xq22.3 HERV-W Env is glycosylated, forms oligomers, and is expressed at the cell surface. In contrast, Xq22.3 HERV-W Env is unglycosylated, does not form oligomers, and is located intracellularly, probably due to lack of a signal peptide. Finally, we reconfirm by immunohistochemistry that monoclonal antibody 6A2B2 detects an antigen expressed in placenta and multiple sclerosis brain lesions. Conclusions A partially defective HERV-W env gene located on chromosome Xq22.3, which we propose to designate ERVWE2, has retained coding capacity and can produce ex vivo an N-terminally truncated Env protein, named N-Trenv. Detection of an antigen by 6A2B2 in placenta and multiple sclerosis lesions opens the possibility that N-Trenv could be expressed in vivo. More generally, our findings are compatible with the idea that defective HERV elements may be capable of producing incomplete HERV proteins that, speculatively, may exert functions in human physiology or pathology.

  5. Human T-Cell Leukemia Virus Type 1 Infection and Adult T-Cell Leukemia.

    Science.gov (United States)

    Chan, Chi-Ping; Kok, Kin-Hang; Jin, Dong-Yan

    2017-01-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus discovered to cause adult T-cell leukemia (ATL), a highly aggressive blood cancer. HTLV-1 research in the past 35 years has been most revealing in the mechanisms of viral oncogenesis. HTLV-1 establishes a lifelong persistent infection in CD4(+) T lymphocytes. The infection outcome is governed by host immunity. ATL develops in 2-5% of infected individuals 30-50 years after initial exposure. HTLV-1 encodes two oncoproteins Tax and HBZ, which are required for initiation of cellular transformation and maintenance of cell proliferation, respectively. HTLV-1 oncogenesis is driven by a clonal selection and expansion process during which both host and viral factors cooperate to impair genome stability, immune surveillance, and other mechanisms of tumor suppression. A better understanding of HTLV-1 biology and leukemogenesis will reveal new strategies and modalities for ATL prevention and treatment.

  6. On the general theory of the origins of retroviruses

    Directory of Open Access Journals (Sweden)

    Wayengera Misaki

    2010-02-01

    Full Text Available Abstract Background The order retroviridae comprises viruses based on ribonucleic acids (RNA. Some, such as HIV and HTLV, are human pathogens. Newly emerged human retroviruses have zoonotic origins. As far as has been established, both repeated infections (themselves possibly responsible for the evolution of viral mutations (Vm and host adaptability (Ha; along with interplay between inhibitors and promoters of cell tropism, are needed to effect retroviral cross-species transmissions. However, the exact modus operadi of intertwine between these factors at molecular level remains to be established. Knowledge of such intertwine could lead to a better understanding of retrovirology and possibly other infectious processes. This study was conducted to derive the mathematical equation of a general theory of the origins of retroviruses. Methods and results On the basis of an arbitrarily non-Euclidian geometrical "thought experiment" involving the cross-species transmission of simian foamy virus (sfv from a non-primate species Xy to Homo sapiens (Hs, initially excluding all social factors, the following was derived. At the port of exit from Xy (where the species barrier, SB, is defined by the Index of Origin, IO, sfv shedding is (1 enhanced by two transmitting tensors (Tt, (i virus-specific immunity (VSI and (ii evolutionary defenses such as APOBEC, RNA interference pathways, and (when present expedited therapeutics (denoted e2D; and (2 opposed by the five accepting scalars (At: (a genomic integration hot spots, gIHS, (b nuclear envelope transit (NMt vectors, (c virus-specific cellular biochemistry, VSCB, (d virus-specific cellular receptor repertoire, VSCR, and (e pH-mediated cell membrane transit, (↓pH CMat. Assuming As and Tt to be independent variables, IO = Tt/As. The same forces acting in an opposing manner determine SB at the port of sfv entry (defined here by the Index of Entry, IE = As/Tt. Overall, If sfv encounters no unforeseen effects on

  7. On the general theory of the origins of retroviruses

    Science.gov (United States)

    2010-01-01

    Background The order retroviridae comprises viruses based on ribonucleic acids (RNA). Some, such as HIV and HTLV, are human pathogens. Newly emerged human retroviruses have zoonotic origins. As far as has been established, both repeated infections (themselves possibly responsible for the evolution of viral mutations (Vm) and host adaptability (Ha)); along with interplay between inhibitors and promoters of cell tropism, are needed to effect retroviral cross-species transmissions. However, the exact modus operadi of intertwine between these factors at molecular level remains to be established. Knowledge of such intertwine could lead to a better understanding of retrovirology and possibly other infectious processes. This study was conducted to derive the mathematical equation of a general theory of the origins of retroviruses. Methods and results On the basis of an arbitrarily non-Euclidian geometrical "thought experiment" involving the cross-species transmission of simian foamy virus (sfv) from a non-primate species Xy to Homo sapiens (Hs), initially excluding all social factors, the following was derived. At the port of exit from Xy (where the species barrier, SB, is defined by the Index of Origin, IO), sfv shedding is (1) enhanced by two transmitting tensors (Tt), (i) virus-specific immunity (VSI) and (ii) evolutionary defenses such as APOBEC, RNA interference pathways, and (when present) expedited therapeutics (denoted e2D); and (2) opposed by the five accepting scalars (At): (a) genomic integration hot spots, gIHS, (b) nuclear envelope transit (NMt) vectors, (c) virus-specific cellular biochemistry, VSCB, (d) virus-specific cellular receptor repertoire, VSCR, and (e) pH-mediated cell membrane transit, (↓pH CMat). Assuming As and Tt to be independent variables, IO = Tt/As. The same forces acting in an opposing manner determine SB at the port of sfv entry (defined here by the Index of Entry, IE = As/Tt). Overall, If sfv encounters no unforeseen effects on transit

  8. Human endogenous retrovirus-FRD envelope protein (syncytin 2 expression in normal and trisomy 21-affected placenta

    Directory of Open Access Journals (Sweden)

    Handschuh Karen

    2008-01-01

    Full Text Available Abstract Human trophoblast expresses two fusogenic retroviral envelope proteins, the widely studied syncytin 1, encoded by HERV-W and the recently characterized syncytin 2 encoded by HERV-FRD. Here we studied syncytin 2 in normal and Trisomy 21-affected placenta associated with abnormal trophoblast differentiation. Syncytin 2 immunolocalization was restricted throughout normal pregnancy to some villous cytotrophoblastic cells (CT. During the second trimester of pregnancy, syncytin 2 was immunolocalized in some cuboidal CT in T21 placentas, whereas in normal placentas it was observed in flat CT, extending into their cytoplasmic processes. In vitro, CT isolated from normal placenta fuse and differentiate into syncytiotrophoblast. At the same time, syncytin 2 transcript levels decreased significantly with syncytiotrophoblast formation. In contrast, CT isolated from T21-affected placentas fused and differentiated poorly and no variation in syncytin 2 transcript levels was observed. Syncytin 2 expression illustrates the abnormal trophoblast differentiation observed in placenta of fetal T21-affected pregnancies.

  9. Human infection with Dermatophilus congolensis.

    Science.gov (United States)

    Kaminski, G W; Suter, I I

    1976-03-27

    Dermatophilosis is a skin disease in animals and humans caused by the actinomycete Dermatophilus congolensis. This microorganism causes the skin disease in sheep commonly referred to in Australia as "lumpy wool" or mycotic dermatitis. One proven case of human dermatophilosis and two cases with features which are clinically highly suggestive of the disease from South Australia are described. There has been only one previous report of human infection caused by D. congolensis, which was from the United States in 1961. A brief account of the history, characteristics and life cycle of D. congolensis is given. Human infection in Australia may be not uncommon. A diagnosis can be made by direct microscopy of scab material from the lesions. For this purpose, dry scabs should be sent to the laboratory.

  10. Avian Influenza infection in Human

    Directory of Open Access Journals (Sweden)

    Mohan. M

    2008-08-01

    Full Text Available Outbreaks caused by the H5N1 strain are presently of the greatest concern for human health. In assessing risks to human health, it is important to know exactly which avian virus strains are causing the outbreaks in birds.All available evidence points to an increased risk of transmission to humans when outbreaks of highly pathogenic avian H5N1 influenza are widespread in poultry. There is mounting evidence that this strain has a unique capacity to jump the species barrier and cause severe disease, with high mortality, in humans. There is no evidence, to date that efficient human to human transmission of H5N1 strain has occurred and very often. Efficient transmission among humans is a key property of pandemic strains and a property that the avian H5N1 and H9N2 viruses apparently lacked. The biological and molecular basis for effective aerosol transmission among humans is not known. The virus can improve its transmissibility among humans via two principal mechanisms. The first is a “reassortment” event, in which genetic material is exchanged between human and avian viruses during co-infection of a human or pig.Reassortment could result in a fully transmissible pandemic virus, announced by a sudden surge of cases with explosive spread. The second mechanism is a more gradual process of adaptive mutation, whereby the capability of the virus to bind to human cells increases during subsequent infections of humans. Adaptive mutation, expressed initially as small clusters of human cases with some evidence of human-to-human transmission, would probably give the world some time to take defensive action, if detected sufficiently early. As the number of human infections grows, the risk increases that a new virus subtype could emerge, triggering an influenza pandemic. Humans as well as swine must now be considered a potential mixing vessel for the generation of such a virus. This link between widespread infection in poultry and increased risk of human

  11. Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Mostafa, Aliehossadat; Jalilvand, Somayeh; Shoja, Zabihollah; Nejati, Ahmad; Shahmahmoodi, Shohreh; Sahraian, Mohammad Ali; Marashi, Sayed Mahdi

    2017-07-01

    The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody. © 2017 Wiley Periodicals, Inc.

  12. Proteasomal degradation of TRIM5alpha during retrovirus restriction.

    Directory of Open Access Journals (Sweden)

    Christopher James Rold

    2008-05-01

    Full Text Available The host protein TRIM5alpha inhibits retroviral infection at an early post-penetration stage by targeting the incoming viral capsid. While the detailed mechanism of restriction remains unclear, recent studies have implicated the activity of cellular proteasomes in the restriction of retroviral reverse transcription imposed by TRIM5alpha. Here, we show that TRIM5alpha is rapidly degraded upon encounter of a restriction-susceptible retroviral core. Inoculation of TRIM5alpha-expressing human 293T cells with a saturating level of HIV-1 particles resulted in accelerated degradation of the HIV-1-restrictive rhesus macaque TRIM5alpha protein but not the nonrestrictive human TRIM5alpha protein. Exposure of cells to HIV-1 also destabilized the owl monkey restriction factor TRIMCyp; this was prevented by addition of the inhibitor cyclosporin A and was not observed with an HIV-1 virus containing a mutation in the capsid protein that relieves restriction by TRIMCyp IVHIV. Likewise, human TRIM5alpha was rapidly degraded upon encounter of the restriction-sensitive N-tropic murine leukemia virus (N-MLV but not the unrestricted B-MLV. Pretreatment of cells with proteasome inhibitors prevented the HIV-1-induced loss of both rhesus macaque TRIM5alpha and TRIMCyp proteins. We also detected degradation of endogenous TRIM5alpha in rhesus macaque cells following HIV-1 infection. We conclude that engagement of a restriction-sensitive retrovirus core results in TRIM5alpha degradation by a proteasome-dependent mechanism.

  13. Viral latency in blood and saliva of simian foamy virus-infected humans.

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    Rejane Rua

    Full Text Available Simian foamy viruses (SFV are widespread retroviruses among non-human primates (NHP. SFV actively replicate in the oral cavity and can be transmitted to humans through NHP bites, giving rise to a persistent infection. We aimed at studying the natural history of SFV infection in human. We have analyzed viral load and gene expression in 14 hunters from Cameroon previously shown to be infected with a gorilla SFV strain. Viral DNA could be detected by quantitative polymerase chain reaction (q-PCR targeting the pol-in region, in most samples of peripheral blood mononuclear cells (PBMCs (7.1 ± 6.0 SFV DNA copies/105 PBMCs and saliva (2.4 ± 4.3 SFV DNA copies/105 cells derived from the hunters. However, quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR revealed the absence of SFV viral gene expression in both PBMCs and saliva, suggesting that SFV was latent in the human samples. Our study demonstrates that a latent infection can occur in humans and persist for years, both in PBMCs and saliva. Such a scenario may contribute to the putative lack of secondary human-to-human transmissions of SFV.

  14. Human genetic susceptibility to Candida infections

    NARCIS (Netherlands)

    Plantinga, T.S.; Johnson, M.D.; Scott, W.K.; Joosten, L.A.B.; Meer, J.W. van der; Perfect, J.R.; Kullberg, B.J.; Netea, M.G.

    2012-01-01

    Infections with Candida spp. have different manifestations in humans, ranging from mucosal to bloodstream and deep-seated disseminated infections. Immunocompromised patients have increased susceptibility to these types of infections, due to reduced capacity to elicit effective innate or adaptive

  15. Isolation of koala retroviruses from koalas in Japan.

    Science.gov (United States)

    Miyazawa, Takayuki; Shojima, Takayuki; Yoshikawa, Rokusuke; Ohata, Takuji

    2011-01-01

    Koala retrovirus (KoRV) is considered to be associated with leukemia, lymphoma and immunodeficiency-like diseases in koalas. We therefore conducted a pilot study of KoRV infection in five Queensland koalas in Kobe Municipal Oji Zoo. By polymerase chain reaction to detect partial env and pol genes of KoRV in genomic DNA isolated from whole blood and feces, all five koalas were found to be positive for KoRV proviruses. We succeeded in culturing koala lymphocytes from less than 1 ml blood for over 14 days in the presence of recombinant human interleukin-2. By coculturing the lymphocytes with human embryonic kidney (HEK) 293T cells, we isolated KoRVs from all five koalas. We designated these isolates as strains OJ-1 to OJ-5. By electron microscopy, we observed C-type retroviral particles in HEK 293T cells chronically infected with KoRV strain OJ-4. This is the first report on the isolation of KoRV from koalas in a Japanese zoo.

  16. Avian Influenza A Virus Infections in Humans

    Science.gov (United States)

    ... Pandemic Other Avian Influenza A Virus Infections in Humans Language: English (US) Español Recommend on Facebook Tweet ... A Viruses Avian Influenza A Virus Infections in Humans Although avian influenza A viruses usually do not ...

  17. Expression of human factor IX in rabbit hepatocytes by retrovirus-mediated gene transfer: Potential for gene therapy of hemophilia B

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, A.R. (Univ. of Washington, Seattle (USA) Puget Sound Blood Center, Seattle, WA (USA)); Darlington, G. (Baylor College of Medicine, Houston, TX (USA)); Armentano, D.; Woo, S.L.C.

    1990-08-01

    Hemophilia B (Christmas disease) is a chromosome X-linked blood clotting disorder which results when factor IX is deficient or functionally defective. The enzyme is synthesized in the liver, and the existence of animal models for this genetic disease will permit the development of somatic gene therapy protocols aimed at transfer of the functional gene into the liver. The authors report the construction of an N2-based recombinant retroviral vector, NCMVFIX, for efficient transfer and expression of human factor IX cDNA in primary rabbit hepatocytes. In this construct the human cytomegalovirus immediate early promoter directs the expression of factor IX. Hepatocytes were isolated from 3-week-old New Zealand White rabbits, infected with the recombinant virus, and analyzed for secretion of active factor IX. The infected rabbit hepatocytes produced human factor IX that is indistinguishable from enzyme derived from normal human plasma. The recombinant protein is sufficiently {gamma}-carboxylated and is functionally active in clotting assays. These results establish the feasibility of using infected hepatocytes for the expression of this protein and are a step toward the goal of correcting hemophilia B by hepatic gene transfer.

  18. Clinical Aspects of Feline Retroviruses: A Review

    Directory of Open Access Journals (Sweden)

    Katrin Hartmann

    2012-10-01

    Full Text Available Feline leukemia virus (FeLV and feline immunodeficiency virus (FIV are retroviruses with global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma, bone marrow suppression syndromes (mainly anemia, and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less commonly diagnosed than in the previous 20 years; prevalence has been decreasing in most countries. However, FeLV importance may be underestimated as it has been shown that regressively infected cats (that are negative in routinely used FeLV tests also can develop clinical signs. FIV can cause an acquired immunodeficiency syndrome that increases the risk of opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. This article provides a review of clinical syndromes in progressively and regressively FeLV-infected cats as well as in FIV-infected cats.

  19. Clinical aspects of feline retroviruses: a review.

    Science.gov (United States)

    Hartmann, Katrin

    2012-10-31

    Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia), and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less commonly diagnosed than in the previous 20 years; prevalence has been decreasing in most countries. However, FeLV importance may be underestimated as it has been shown that regressively infected cats (that are negative in routinely used FeLV tests) also can develop clinical signs. FIV can cause an acquired immunodeficiency syndrome that increases the risk of opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. This article provides a review of clinical syndromes in progressively and regressively FeLV-infected cats as well as in FIV-infected cats.

  20. Clinical Aspects of Feline Retroviruses: A Review

    Science.gov (United States)

    Hartmann, Katrin

    2012-01-01

    Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia), and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less commonly diagnosed than in the previous 20 years; prevalence has been decreasing in most countries. However, FeLV importance may be underestimated as it has been shown that regressively infected cats (that are negative in routinely used FeLV tests) also can develop clinical signs. FIV can cause an acquired immunodeficiency syndrome that increases the risk of opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. This article provides a review of clinical syndromes in progressively and regressively FeLV-infected cats as well as in FIV-infected cats. PMID:23202500

  1. [Using GFP retrovirus to label tumor cells and vascular endothelia cells].

    Science.gov (United States)

    Xie, K; Xu, P; Gu, Q; Liu, W; Wang, F; Tian, Y; Chen, X; Li, C; Huang, Q

    2001-02-20

    To prepare retrovirus which carry GFP gene and are able to label living cells simply and rapidly. The recombinant retroviral vector pLNCX-GFP was constructed by inserting 780?bp GFP cDNA fragment into the MCS site of retroviral plasmid pLNCX. Both ecotropic packaging cell line ΦX-Eco and amphotropic packaging cell line ΦX-Ampho and PA317 were transfected by pLNCX-GFP with liposome. The supernate collected from transfected packaging cells was used to infect a variety of tumor cell lines and vascular endothelia cell lines. When packaging cells were transfected by retroviral vector pLNCX-GFP, the GFP expression could be observed in 25%-40% of cells and GFP retrovirus then could be detected, however G418 resistant clones showed more stable GFP expression and higher retrovirus titer. The GFP retrovirus from different packaging cell line showed variant ability to infect tumor cell lines and vascular endothelia cell lines and the tumor cells infected by GFP retrovirus showed stable GFP expression in vitro. GFP transduced tumor cells could grow in syngenic animal and continue expressing GFP. Using GFP retrovirus to label target cells represent an important advantage over conventional plasmid because they can efficiently transfer GFP gene into target cells and GFP can be stably expressed in target cells no matter in vitro or in vivo.

  2. Human APOBEC3 induced mutation of human immunodeficiency virus type-1 contributes to adaptation and evolution in natural infection.

    Directory of Open Access Journals (Sweden)

    Eun-Young Kim

    2014-07-01

    Full Text Available Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A mutagenesis and inhibit synthesis of nascent human immunodeficiency virus-type 1 (HIV-1 cDNA. Human APOBEC3 proteins have additionally been proposed to induce infrequent, potentially non-lethal G-to-A mutations that make subtle contributions to sequence diversification of the viral genome and adaptation though acquisition of beneficial mutations. Using single-cycle HIV-1 infections in culture and highly parallel DNA sequencing, we defined trinucleotide contexts of the edited sites for APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H. We then compared these APOBEC3 editing contexts with the patterns of G-to-A mutations in HIV-1 DNA in cells obtained sequentially from ten patients with primary HIV-1 infection. Viral substitutions were highest in the preferred trinucleotide contexts of the edited sites for the APOBEC3 deaminases. Consistent with the effects of immune selection, amino acid changes accumulated at the APOBEC3 editing contexts located within human leukocyte antigen (HLA-appropriate epitopes that are known or predicted to enable peptide binding. Thus, APOBEC3 activity may induce mutations that influence the genetic diversity and adaptation of the HIV-1 population in natural infection.

  3. Lack of evidence for human T cell lymphotrophic virus type I or II infection in patients with systemic lupus erythematosus or rheumatoid arthritis.

    Science.gov (United States)

    Bailer, R T; Lazo, A; Harisdangkul, V; Ehrlich, G D; Gray, L S; Whisler, R L; Blakeslee, J R

    1994-12-01

    Human retroviruses including human immunodeficiency virus (HIV) and human T cell lymphotrophic virus Types I and II (HTLV-I/II) have been associated with forms of connective tissue autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We looked for evidence of HTLV-I/II infection in a large population of SLE, RA, and control patients. One hundred fifteen patients with connective tissue autoimmune disease and other rheumatological disorders were screened for antibodies to HTLV-I/II by Western immunoblots (WIB). Due to the transforming characteristic of these retroviruses, the patients' peripheral blood mononuclear cells (PBMNC) were cultured in attempts to establish continuous cell lines. Furthermore, PBMNC culture supernatants were analyzed for reverse transcriptase activity and/or HTLV-I/II gag antigen production. The presence of HTLV-I/II proviral sequences in short term culture and fresh PBMNC was determined by Southern blot analysis and polymerase chain reaction (PCR), respectively. respectively. All 115 patients were HTLV-I/II and HIV seronegative. Seventy-four attempts to establish PBMNC cell lines from 65 patients were unsuccessful with a mean culture survival time of 3.6 (+/- 1.4) months. Reverse transcriptase activity and HTLV-I/II gag antigen production were not detected in 51 and 16 culture supernatants tested, respectively. Cells from 11 patients tested by Southern blot analysis and from 57 patients tested by PCR were negative for HTLV-I/II related sequences. Our results failed to establish an association between human retroviruses (HTLV-I/II and HIV) and SLE, RA, or other rheumatological disorders. However, these results do not rule out other exogenous or endogenous retroviruses that may play a role in the initiation and/or promotion of these diseases.

  4. Macroevolution of complex retroviruses

    DEFF Research Database (Denmark)

    Katzourakis, Aris; Gifford, Robert J; Tristem, Michael

    2009-01-01

    viruses were infecting mammals more than 100 million years ago and codiverged with their hosts across an entire geological era. Our analysis highlights the role of evolutionary constraint in maintaining viral genome structure and indicates that accessory genes and mammalian mechanisms of innate immunity...... are the products of macroevolutionary conflict played out over a geological time scale....

  5. The DNA copy number of human endogenous retrovirus-W (MSRV-type is increased in multiple sclerosis patients and is influenced by gender and disease severity.

    Directory of Open Access Journals (Sweden)

    Marta Garcia-Montojo

    Full Text Available BACKGROUND: Multiple sclerosis is an autoimmune disease more prevalent in women than in men. Multiple Sclerosis Associated Retrovirus element (MSRV is a member of type-W endogenous retrovirus family (HERV-W, known to be associated to MS. Most HERVs are unable to replicate but MSRV expression associated with reverse-transcriptase activity in MS would explain reported DNA copy number increase in MS patients. A potential link between HERV-W copies on chromosome X and gender differential prevalence has been suggested. The present study addresses MSRV-type DNA load in relation with the gender differences and clinical status in MS and healthy controls. RESULTS: 178 MS patients (62.9% women and 124 controls (56.5% women were included. MSRV env load (copies/pg of DNA was analyzed by real time qPCR with specific primers and probe for its env gene, in DNA from peripheral blood mononuclear cells (PBMCs. MSRV load was more elevated in MS patients than in controls (p = 4.15e-7. MS women presented higher MSRV load than control women (p = 0.009 and MS men also had higher load than control men (p = 2.77e-6. Besides, women had higher levels than men, both among patients (p = 0.007 and controls (p = 1.24e-6. Concordantly, EDSS and MSSS scores were higher among female patients with an elevated MSRV load (p = 0.03 and p = 0.04, respectively. CONCLUSIONS: MSRV increases its copy number in PBMC of MS patients and particularly in women with high clinical scores. This may explain causes underlying the higher prevalence of MS in women. The association with the clinical severity calls for further investigations on MSRV load in PBMCs as a biomarker for MS.

  6. Restriction genes for retroviruses influence the risk of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Bjørn A Nexø

    Full Text Available We recently described that the autoimmune, central nervous system disease, multiple sclerosis (MS, is genetically associated with the human endogenous retroviral locus, HERV-Fc1, in Scandinavians. A number of dominant human genes encoding factors that restrict retrovirus replication have been known for a long time. Today human restriction genes for retroviruses include amongst others TRIMs, APOBEC3s, BST2 and TREXs. We have therefore looked for a role of these retroviral restriction genes in MS using genetic epidemiology. We here report that markers in two TRIMs, TRIM5 and TRIM22 and a marker in BST2, associated statistically with the risk of getting MS, while markers in or near APOBEC3s and TREXs showed little or no effect. This indicates that the two TRIMs and BST2 influence the risk of disease and thus supports the hypothesis of a viral involvement.

  7. Two distinct variants of simian foamy virus in naturally infected mandrills (Mandrillus sphinx) and cross-species transmission to humans.

    Science.gov (United States)

    Mouinga-Ondémé, Augustin; Betsem, Edouard; Caron, Mélanie; Makuwa, Maria; Sallé, Bettina; Renault, Noemie; Saib, Ali; Telfer, Paul; Marx, Preston; Gessain, Antoine; Kazanji, Mirdad

    2010-12-14

    Each of the pathogenic human retroviruses (HIV-1/2 and HTLV-1) has a nonhuman primate counterpart, and the presence of these retroviruses in humans results from interspecies transmission. The passage of another simian retrovirus, simian foamy virus (SFV), from apes or monkeys to humans has been reported. Mandrillus sphinx, a monkey species living in central Africa, is naturally infected with SFV. We evaluated the natural history of the virus in a free-ranging colony of mandrills and investigated possible transmission of mandrill SFV to humans. We studied 84 semi-free-ranging captive mandrills at the Primate Centre of the Centre International de Recherches Médicales de Franceville (Gabon) and 15 wild mandrills caught in various areas of the country. The presence of SFV was also evaluated in 20 people who worked closely with mandrills and other nonhuman primates. SFV infection was determined by specific serological (Western blot) and molecular (nested PCR of the integrase region in the polymerase gene) assays. Seropositivity for SFV was found in 70/84 (83%) captive and 9/15 (60%) wild-caught mandrills and in 2/20 (10%) humans. The 425-bp SFV integrase fragment was detected in peripheral blood DNA from 53 captive and 8 wild-caught mandrills and in two personnel. Sequence and phylogenetic studies demonstrated the presence of two distinct strains of mandrill SFV, one clade including SFVs from mandrills living in the northern part of Gabon and the second consisting of SFV from animals living in the south. One man who had been bitten 10 years earlier by a mandrill and another bitten 22 years earlier by a macaque were found to be SFV infected, both at the Primate Centre. The second man had a sequence close to SFVmac sequences. Comparative sequence analysis of the virus from the first man and from the mandrill showed nearly identical sequences, indicating genetic stability of SFV over time. Our results show a high prevalence of SFV infection in a semi-free-ranging colony

  8. Two distinct variants of simian foamy virus in naturally infected mandrills (Mandrillus sphinx and cross-species transmission to humans

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    Marx Preston

    2010-12-01

    Full Text Available Abstract Background Each of the pathogenic human retroviruses (HIV-1/2 and HTLV-1 has a nonhuman primate counterpart, and the presence of these retroviruses in humans results from interspecies transmission. The passage of another simian retrovirus, simian foamy virus (SFV, from apes or monkeys to humans has been reported. Mandrillus sphinx, a monkey species living in central Africa, is naturally infected with SFV. We evaluated the natural history of the virus in a free-ranging colony of mandrills and investigated possible transmission of mandrill SFV to humans. Results We studied 84 semi-free-ranging captive mandrills at the Primate Centre of the Centre International de Recherches Médicales de Franceville (Gabon and 15 wild mandrills caught in various areas of the country. The presence of SFV was also evaluated in 20 people who worked closely with mandrills and other nonhuman primates. SFV infection was determined by specific serological (Western blot and molecular (nested PCR of the integrase region in the polymerase gene assays. Seropositivity for SFV was found in 70/84 (83% captive and 9/15 (60% wild-caught mandrills and in 2/20 (10% humans. The 425-bp SFV integrase fragment was detected in peripheral blood DNA from 53 captive and 8 wild-caught mandrills and in two personnel. Sequence and phylogenetic studies demonstrated the presence of two distinct strains of mandrill SFV, one clade including SFVs from mandrills living in the northern part of Gabon and the second consisting of SFV from animals living in the south. One man who had been bitten 10 years earlier by a mandrill and another bitten 22 years earlier by a macaque were found to be SFV infected, both at the Primate Centre. The second man had a sequence close to SFVmac sequences. Comparative sequence analysis of the virus from the first man and from the mandrill showed nearly identical sequences, indicating genetic stability of SFV over time. Conclusion Our results show a high

  9. The impact of p53 on the early stage replication of retrovirus.

    Science.gov (United States)

    Kinnetz, Michaela; Alghamdi, Faris; Racz, Michael; Hu, Wenwei; Shi, Binshan

    2017-08-09

    The function of p53 in cancer biology has been studied extensively, but its role in anti-retrovirus infection has been elusive for many years. The restriction of retrovirus early stage replication by p53 was investigated in this study. VSV-G pseudotyped retrovirus with GFP reporter gene was used to infect both HCT116 p53(+/+) cells and its isogenic p53 knockout HCT116 p53(-/-) cells. The infection was detected by flow cytometry. Reverse transcription products were quantified by real time PCR. Mutation analysis was performed after 1-LTR cycle and 2-LTR cycle DNA were amplified and PCR products were sequenced. Transcription and translation of cyclin-dependent kinase inhibitor 1 (p21(Cip1)) and SAM domain and HD domain-containing protein 1 (SAMHD1) were analyzed by TaqMan PCR and Western blot experiments. siRNA experiment was applied to study the role of p53 downstream gene p21(Cip1) in the restriction of retrovirus infection. It was found that the block of retrovirus infection in non-cycling cells was significantly attenuated in HCT116 p53(-/-) cells when compared to HCT116 p53(+/+) cells. It was found that both late reverse transcription products and viral 2-LTR cycle DNA were significantly increased in infected non-cycling HCT116 p53(-/-) cells. Furthermore, the mutation frequency detected in 1-LTR DNA from HCT116 p53(+/+) cells were significantly decreased in comparison to HCT116 p53(-/-) cells. A higher number of insertion and deletion mutations were detected in the joint region of 2-LTR cycle DNA in infected p53(+/+) cells. Cell cycle analysis showed retrovirus infection promoted host cell replication. Higher levels of mRNA and protein of p21(Cip1) were found in HCT116 p53(+/+) cells in comparison to the HCT116 p53(-/-) cells. Furthermore, knockdown of p21(Cip1) in non-cycling HCT116 p53(+/+) cells significantly increased the infection. The results of this study showed that p53 is an important restriction factor that interferes with retrovirus infection in its

  10. Contamination of live attenuated vaccines with an infectious feline endogenous retrovirus (RD-114 virus).

    Science.gov (United States)

    Yoshikawa, Rokusuke; Shimode, Sayumi; Sakaguchi, Shoichi; Miyazawa, Takayuki

    2014-03-01

    Retroviruses are classified as exogenous and endogenous retroviruses according to the mode of transmission. Endogenous retroviruses (ERVs) are retroviruses which have been integrated into germ-line cells and inherited from parents to offspring. Most ERVs are inactivated by deletions and mutations; however, certain ERVs maintain their infectivity and infect the same host and new hosts as exogenous retroviruses. All domestic cats have infectious ERVs, termed RD-114 virus. Several canine and feline attenuated vaccines are manufactured using RD-114 virus-producing cell lines such as Crandell-Rees feline kidney cells; therefore, it is possible that infectious RD-114 virus contaminates live attenuated vaccines. Recently, Japanese and UK research groups found that several feline and canine vaccines were indeed contaminated with infectious RD-114 virus. This was the first incidence of contamination of 'infectious' ERVs in live attenuated vaccines. RD-114 virus replicates efficiently in canine cell lines and primary cells. Therefore, it is possible that RD-114 virus infects dogs following inoculation with contaminated vaccines and induces proliferative diseases and immune suppression, if it adapts to grow efficiently in dogs. In this review, we summarize the incidence of contamination of RD-114 virus in live attenuated vaccines and potential risks of infection with RD-114 virus in dogs.

  11. Computational Evaluation of the Strict Master and Random Template Models of Endogenous Retrovirus Evolution.

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    Fabrícia F Nascimento

    Full Text Available Transposable elements (TEs are DNA sequences that are able to replicate and move within and between host genomes. Their mechanism of replication is also shared with endogenous retroviruses (ERVs, which are also a type of TE that represent an ancient retroviral infection within animal genomes. Two models have been proposed to explain TE proliferation in host genomes: the strict master model (SMM, and the random template (or transposon model (TM. In SMM only a single copy of a given TE lineage is able to replicate, and all other genomic copies of TEs are derived from that master copy. In TM, any element of a given family is able to replicate in the host genome. In this paper, we simulated ERV phylogenetic trees under variations of SMM and TM. To test whether current phylogenetic programs can recover the simulated ERV phylogenies, DNA sequence alignments were simulated and maximum likelihood trees were reconstructed and compared to the simulated phylogenies. Results indicate that visual inspection of phylogenetic trees alone can be misleading. However, if a set of statistical summaries is calculated, we are able to distinguish between models with high accuracy by using a data mining algorithm that we introduce here. We also demonstrate the use of our data mining algorithm with empirical data for the porcine endogenous retrovirus (PERV, an ERV that is able to replicate in human and pig cells in vitro.

  12. Human papillomavirus type 13 infecting the conjunctiva.

    Science.gov (United States)

    Benevides dos Santos, Paulo José; Borborema dos Santos, Cristina Maria; Rufino Mendonça, Rosângela; Vieira do Carmo, Maria Auxiliadora; Astofi-Filho, Spartaco

    2005-09-01

    Focal epithelial hyperplasia (FEH) is a rare infection caused by human papillomavirus (HPV) types 13 or 32 believed to infect exclusively oral mucosa. This report illustrates a case of multiple conjunctival papillomas similar to oral FEH caused by HPV-13, consisting in the first description of its infection outside the oral mucosa in a healthy patient.

  13. Subpopulations of M-MDSCs from mice infected by an immunodeficiency-causing retrovirus and their differential suppression of T- vs B-cell responses.

    Science.gov (United States)

    O'Connor, Megan A; Fu, Whitney W; Green, Kathy A; Green, William R

    2015-11-01

    Monocytic (CD11b(+)Ly6G(±/Lo)Ly6C(+)) myeloid derived suppressor cells (M-MDSCs) expand following murine retroviral LP-BM5 infection and suppress ex vivo polyclonal T-cell and B-cell responses. M-MDSCs 3 weeks post LP-BM5 infection have decreased suppression of T-cell, but not B-cell, responses and alterations in the degree of iNOS/NO dependence of suppression. M-MDSCs from LP-BM5 infected mice were sorted into four quadrant populations (Ly6C/CD11b density): all quadrants suppressed B-cell responses, but only M-MDSCs expressing the highest levels of Ly6C and CD11b (Q2) significantly suppressed T-cell responses. Further subdivision of this Q2 population revealed the Ly6C(+/Hi) M-MDSC subpopulation as the most suppressive, inhibiting T- and B-cell responses in a full, or partially, iNOS/NO-dependent manner, respectively. In contrast, the lower/moderate levels of suppression by the Ly6C(+/Lo) and Ly6C(+/Mid) M-MDSC Q2 subpopulations, whether versus T- and/or B-cells, displayed little/no iNOS dependency for suppression. These results highlight differential phenotypic and functional immunosuppressive M-MDSC subsets in a retroviral immunodeficiency model. Published by Elsevier Inc.

  14. Modulating drug resistance by targeting BCRP/ABCG2 using retrovirus-mediated RNA interference.

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    Ni Xie

    Full Text Available The BCRP/ABCG2 transporter, which mediates drug resistance in many types of cells, depends on energy provided by ATP hydrolysis. Here, a retrovirus encoding a shRNA targeting the ATP-binding domain of this protein was used to screen for highly efficient agents that could reverse drug resistance and improve cell sensitivity to drugs, thus laying the foundation for further studies and applications.To target the ATP-binding domain of BCRP/ABCG2, pLenti6/BCRPsi shRNA recombinant retroviruses, with 20 bp target sequences starting from the 270th, 745th and 939th bps of the 6th exon, were constructed and packaged. The pLenti6/BCRPsi retroviruses (V-BCRPi that conferred significant knockdown effects were screened using a drug-sensitivity experiment and flow cytometry. The human choriocarcinoma cell line JAR, which highly expresses endogenous BCRP/ABCG2, was injected under the dorsal skin of a hairless mouse to initiate a JAR cytoma. After injecting V-BCRPi-infected JAR tumor cells into the dorsal skin of hairless mice, BCRP/ABCG2 expression in the tumor tissue was determined using immunohistochemistry, fluorescent quantitative RT-PCR and Western blot analyses. After intraperitoneal injection of BCRP/ABCG2-tolerant 5-FU, the tumor volume, weight change, and apoptosis rate of the tumor tissue were determined using in situ hybridization. V-BCRPi increased the sensitivity of the tumor histiocytes to 5-FU and improved the cell apoptosis-promoting effects of 5-FU in the tumor.The goal of the in vivo and in vitro studies was to screen for an RNA interference recombinant retrovirus capable of stably targeting the ATP-binding domain of BCRP/ABCG2 (V-BCRPi to inhibit its function. A new method to improve the chemo-sensitivity of breast cancer and other tumor cells was discovered, and this method could be used for gene therapy and functional studies of malignant tumors.

  15. Modulating drug resistance by targeting BCRP/ABCG2 using retrovirus-mediated RNA interference.

    Science.gov (United States)

    Xie, Ni; Mou, Lisha; Yuan, Jianhui; Liu, Wenlan; Deng, Tingting; Li, Zigang; Jing, Yi; Jin, Yi; Hu, Zhangli

    2014-01-01

    The BCRP/ABCG2 transporter, which mediates drug resistance in many types of cells, depends on energy provided by ATP hydrolysis. Here, a retrovirus encoding a shRNA targeting the ATP-binding domain of this protein was used to screen for highly efficient agents that could reverse drug resistance and improve cell sensitivity to drugs, thus laying the foundation for further studies and applications. To target the ATP-binding domain of BCRP/ABCG2, pLenti6/BCRPsi shRNA recombinant retroviruses, with 20 bp target sequences starting from the 270th, 745th and 939th bps of the 6th exon, were constructed and packaged. The pLenti6/BCRPsi retroviruses (V-BCRPi) that conferred significant knockdown effects were screened using a drug-sensitivity experiment and flow cytometry. The human choriocarcinoma cell line JAR, which highly expresses endogenous BCRP/ABCG2, was injected under the dorsal skin of a hairless mouse to initiate a JAR cytoma. After injecting V-BCRPi-infected JAR tumor cells into the dorsal skin of hairless mice, BCRP/ABCG2 expression in the tumor tissue was determined using immunohistochemistry, fluorescent quantitative RT-PCR and Western blot analyses. After intraperitoneal injection of BCRP/ABCG2-tolerant 5-FU, the tumor volume, weight change, and apoptosis rate of the tumor tissue were determined using in situ hybridization. V-BCRPi increased the sensitivity of the tumor histiocytes to 5-FU and improved the cell apoptosis-promoting effects of 5-FU in the tumor. The goal of the in vivo and in vitro studies was to screen for an RNA interference recombinant retrovirus capable of stably targeting the ATP-binding domain of BCRP/ABCG2 (V-BCRPi) to inhibit its function. A new method to improve the chemo-sensitivity of breast cancer and other tumor cells was discovered, and this method could be used for gene therapy and functional studies of malignant tumors.

  16. Human Infections and Detection of Plasmodium knowlesi

    Science.gov (United States)

    Daneshvar, Cyrus

    2013-01-01

    SUMMARY Plasmodium knowlesi is a malaria parasite that is found in nature in long-tailed and pig-tailed macaques. Naturally acquired human infections were thought to be extremely rare until a large focus of human infections was reported in 2004 in Sarawak, Malaysian Borneo. Human infections have since been described throughout Southeast Asia, and P. knowlesi is now recognized as the fifth species of Plasmodium causing malaria in humans. The molecular, entomological, and epidemiological data indicate that human infections with P. knowlesi are not newly emergent and that knowlesi malaria is primarily a zoonosis. Human infections were undiagnosed until molecular detection methods that could distinguish P. knowlesi from the morphologically similar human malaria parasite P. malariae became available. P. knowlesi infections cause a spectrum of disease and are potentially fatal, but if detected early enough, infections in humans are readily treatable. In this review on knowlesi malaria, we describe the early studies on P. knowlesi and focus on the epidemiology, diagnosis, clinical aspects, and treatment of knowlesi malaria. We also discuss the gaps in our knowledge and the challenges that lie ahead in studying the epidemiology and pathogenesis of knowlesi malaria and in the prevention and control of this zoonotic infection. PMID:23554413

  17. Revealing the history of domesticated sheep using retrovirus integrations

    DEFF Research Database (Denmark)

    Chessa, Bernado; Pereira, Filipe; Arnaud, Frederick

    2009-01-01

    The domestication of livestock represented a crucial step in human history. By using endogenous retroviruses as genetic markers, we found that sheep differentiated on the basis of their "retrotype" and morphological traits dispersed across Eurasia and Africa via separate migratory episodes. Relicts...... production traits, shaped the great majority of present-day breeds. The ability to differentiate genetically primitive sheep from more modern breeds provides valuable insights into the history of sheep domestication...

  18. Ultrasound enhances retrovirus-mediated gene transfer.

    Science.gov (United States)

    Naka, Toshio; Sakoda, Tsuyoshi; Doi, Takashi; Tsujino, Takeshi; Masuyama, Tohru; Kawashima, Seinosuke; Iwasaki, Tadaaki; Ohyanagi, Mitsumasa

    2007-01-01

    Viral vector systems are efficient for transfection of foreign genes into many tissues. Especially, retrovirus based vectors integrate the transgene into the genome of the target cells, which can sustain long term expression. However, it has been demonstrated that the transduction efficiency using retrovirus is relatively lower than those of other viruses. Ultrasound was recently reported to increase gene expression using plasmid DNA, with or without, a delivery vehicle. However, there are no reports, which show an ultrasound effect to retrovirus-mediated gene transfer efficiency. Retrovirus-mediated gene transfer systems were used for transfection of 293T cells, bovine aortic endothelial cells (BAECs), rat aortic smooth muscle cells (RASMCs), and rat skeletal muscle myoblasts (L6 cells) with beta-galactosidase (beta-Gal) genes. Transduction efficiency and cell viability assay were performed on 293T cells that were exposed to varying durations (5 to 30 seconds) and power levels (1.0 watts/cm(2) to 4.0 watts/cm(2)) of ultrasound after being transduced by a retrovirus. Effects of ultrasound to the retrovirus itself was evaluated by transduction efficiency of 293T cells. After exposure to varying power levels of ultrasound to a retrovirus for 5 seconds, 293T cells were transduced by a retrovirus, and transduction efficiency was evaluated. Below 1.0 watts/cm(2) and 5 seconds exposure, ultrasound showed increased transduction efficiency and no cytotoxicity to 293T cells transduced by a retrovirus. Also, ultrasound showed no toxicity to the virus itself at the same condition. Exposure of 5 seconds at the power of 1.0 watts/cm(2) of an ultrasound resulted in significant increases in retrovirus-mediated gene expression in all four cell types tested in this experiment. Transduction efficiencies by ultrasound were enhanced 6.6-fold, 4.8-fold, 2.3-fold, and 3.2-fold in 293T cells, BAECs, RASMCs, and L6 cells, respectively. Furthermore, beta-Gal activities were also increased

  19. The Spectrum of Fungi That Infects Humans

    Science.gov (United States)

    Köhler, Julia R.; Casadevall, Arturo; Perfect, John

    2015-01-01

    Few among the millions of fungal species fulfill four basic conditions necessary to infect humans: high temperature tolerance, ability to invade the human host, lysis and absorption of human tissue, and resistance to the human immune system. In previously healthy individuals, invasive fungal disease is rare because animals’ sophisticated immune systems evolved in constant response to fungal challenges. In contrast, fungal diseases occur frequently in immunocompromised patients. Paradoxically, successes of modern medicine have put increasing numbers of patients at risk for invasive fungal infections. Uncontrolled HIV infection additionally makes millions vulnerable to lethal fungal diseases. A concerted scientific and social effort is needed to meet these challenges. PMID:25367975

  20. Toxoplasma gondii infection in humans in China

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    He Shenyi

    2011-08-01

    Full Text Available Abstract Toxoplasmosis is a zoonotic infection of humans and animals, caused by the opportunistic protozoan Toxoplasma gondii, a parasite belonging to the phylum Apicomplexa. Infection in pregnant women may lead to abortion, stillbirth or other serious consequences in newborns. Infection in immunocompromised patients can be fatal if not treated. On average, one third of people are chronically infected worldwide. Although very limited information from China has been published in the English journals, T. gondii infection is actually a significant human health problem in China. In the present article, we reviewed the clinical features, transmission, prevalence of T. gondii infection in humans in China, and summarized genetic characterizations of reported T. gondii isolates. Educating the public about the risks associated with unhealthy food and life style habits, tracking serological examinations to special populations, and measures to strengthen food and occupational safety are discussed.

  1. A computational model for predicting integrase catalytic domain of retrovirus.

    Science.gov (United States)

    Wu, Sijia; Han, Jiuqiang; Zhang, Xinman; Zhong, Dexing; Liu, Ruiling

    2017-06-21

    Integrase catalytic domain (ICD) is an essential part in the retrovirus for integration reaction, which enables its newly synthesized DNA to be incorporated into the DNA of infected cells. Owing to the crucial role of ICD for the retroviral replication and the absence of an equivalent of integrase in host cells, it is comprehensible that ICD is a promising drug target for therapeutic intervention. However, annotated ICDs in UniProtKB database have still been insufficient for a good understanding of their statistical characteristics so far. Accordingly, it is of great importance to put forward a computational ICD model in this work to annotate these domains in the retroviruses. The proposed model then discovered 11,660 new putative ICDs after scanning sequences without ICD annotations. Subsequently in order to provide much confidence in ICD prediction, it was tested under different cross-validation methods, compared with other database search tools, and verified on independent datasets. Furthermore, an evolutionary analysis performed on the annotated ICDs of retroviruses revealed a tight connection between ICD and retroviral classification. All the datasets involved in this paper and the application software tool of this model can be available for free download at https://sourceforge.net/projects/icdtool/files/?source=navbar. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The cell biology of HIV-1 and other retroviruses

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    Mouland Andrew J

    2006-11-01

    Full Text Available Abstract In recognition of the growing influence of cell biology in retrovirus research, we recently organized a Summer conference sponsored by the American Society for Cell Biology (ASCB on the Cell Biology of HIV-1 and other Retroviruses (July 20–23, 2006, Emory University, Atlanta, Georgia. The meeting brought together a number of leading investigators interested in the interplay between cell biology and retrovirology with an emphasis on presentation of new and unpublished data. The conference was arranged from early to late events in the virus replication cycle, with sessions on viral fusion, entry, and transmission; post-entry restrictions to retroviral infection; nuclear import and integration; gene expression/regulation of retroviral Gag and genomic RNA; and assembly/release. In this review, we will attempt to touch briefly on some of the highlights of the conference, and will emphasize themes and trends that emerged at the meeting. Meeting report The conference began with a keynote address from W. Sundquist on the biochemistry of HIV-1 budding. This presentation will be described in the section on Assembly and Release of Retroviruses.

  3. Dual Simian Foamy Virus/Human Immunodeficiency Virus Type 1 Infections in Persons from Côte d'Ivoire.

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    William M Switzer

    Full Text Available Zoonotic transmission of simian retroviruses in West-Central Africa occurring in primate hunters has resulted in pandemic spread of human immunodeficiency viruses (HIVs and human T-lymphotropic viruses (HTLVs. While simian foamy virus (SFV and simian T- lymphotropic virus (STLV-like infection were reported in healthy persons exposed to nonhuman primates (NHPs in West-Central Africa, less is known about the distribution of these viruses in Western Africa and in hospitalized populations. We serologically screened for SFV and STLV infection using 1,529 specimens collected between 1985 and 1997 from Côte d'Ivoire patients with high HIV prevalence. PCR amplification and analysis of SFV, STLV, and HIV/SIV sequences from PBMCs was used to investigate possible simian origin of infection. We confirmed SFV antibodies in three persons (0.2%, two of whom were HIV-1-infected. SFV polymerase (pol and LTR sequences were detected in PBMC DNA available for one HIV-infected person. Phylogenetic comparisons with new SFV sequences from African guenons showed infection likely originated from a Chlorocebus sabaeus monkey endemic to Côte d'Ivoire. 4.6% of persons were HTLV seropositive and PCR testing of PBMCs from 15 HTLV seroreactive persons identified nine with HTLV-1 and one with HTLV-2 LTR sequences. Phylogenetic analysis showed that two persons had STLV-1-like infections, seven were HTLV-1, and one was an HTLV-2 infection. 310/858 (53%, 8/858 (0.93%, and 18/858 (2.1% were HIV-1, HIV-2, and HIV-positive but undifferentiated by serology, respectively. No SIV sequences were found in persons with HIV-2 antibodies (n = 1 or with undifferentiated HIV results (n = 7. We document SFV, STLV-1-like, and dual SFV/HIV infection in Côte d'Ivoire expanding the geographic range for zoonotic simian retrovirus transmission to West Africa. These findings highlight the need to define the public health consequences of these infections. Studying dual HIV-1/SFV infections in

  4. Gene transfer by retrovirus-derived shuttle vectors in the generation of murine bispecific monoclonal antibodies.

    Science.gov (United States)

    DeMonte, L B; Nistico, P; Tecce, R; Dellabona, P; Momo, M; Anichini, A; Mariani, M; Natali, P G; Malavasi, F

    1990-01-01

    The present study reports on the use of gene transfer by retrovirus-derived shuttle vectors in the generation of hybrid hybridomas secreting bispecific monoclonal antibodies. neo- and dhfr- genes were infected into distinct murine hybridomas, thus conferring a dominant resistance trait to geneticin (G418) and to methotrexate. The vectors employed were replication-deficient and dependent on complementation by a helper virus provided by the irradiated packaging lines. After cocultivation with the relevant packaging cell lines, stable hybridoma lines expressing the selectable markers were easily obtained and were then suitable for conventional somatic fusion. This high-efficiency method was used to generate two bispecific monoclonal antibodies simultaneously targeting molecules expressed on cytotoxic cells (i.e., T lymphocytes and natural killer cells) against a human melanoma-associated antigen. Images PMID:2326256

  5. ISDTool 2.0: a computational model for predicting immunosuppressive domain of retroviruses.

    Science.gov (United States)

    Lv, Hongqiang; Han, Jiuqiang; Liu, Jun; Zheng, Jiguang; Zhong, Dexing; Liu, Ruiling

    2014-11-07

    Immunosuppressive domain (ISD) is a conserved region of transmembrane proteins (TM) in envelope gene (env) of retroviruses. in vitro and vivo, a synthetic peptide (CKS-17) that shows homology to ISD inhibits immune function. Evidence has shown that ISD suppresses lymphocyte proliferation and allows escape from immune effectors of the innate and adaptive arms in mouse immune system. Previously, we have developed a tool ISDTool 1.0 to identify ISD of human endogenous retrovirus (HERV). However, several other important retroviruses exist and no method is devoted to ISD prediction of them so far. In the paper, a computational model is proposed to identify ISD of six typical retroviruses from three species. The model combines the minimum Redundancy Maximum Relevance (mRMR) feature selection criterion with weighted extreme learning machine (WELM) to achieve high identification accuracies of 98.95%, 96.34% and 96.87% using self-consistency, 5-fold and 10-fold cross-validation, respectively. A software tool named ISDTool 2.0 has been developed to facilitate the application of the model and a large number of new putative ISDs of the six retroviruses were predicted. In addition, motifs of ISD in these retroviruses were analyzed and the evolutionary relationship was discussed. Datasets and the software involved in the paper are available at http://sourceforge.net/projects/isdtool/files/ISDTool-2.0/. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Innate imune response against retrovirus.

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    Lucia González

    2015-11-01

    Full Text Available Los retrovirus son un diverso grupo de virus que se encuentran en los vertebrados. Su importancia biomédica radica en que son capaces de infectar humanos, produciendo importantes problemas de salud. El virus de la inmunodeficiencia humana (VIH es capaz de producir un estado de inmunodeficiencia en el huésped determinando el desarrollo de enfermedades oportunistas en estadio avanzados de la enfermedad. Frente a la entrada de un retrovirus al organismo, nuestro sistema inmune presenta como primera línea de defensa a la inmunidad innata. El resultado de esta respuesta es la inducción de interferones de tipo I (IFN tipo I quienes generan un estado antiviral en la célula. Recientemente se ha ampliado la investigación sobre diferentes factores de restricción del huésped que forman parte de la inmunidad innata antiviral determinando la inhibición de la replicación de los retrovirus. En esta revisión abordaremos las distintas vías de señalización implicadas en la función de estos factores. Dentro de ellos, se mencionarán; el SAMHD1 que determina un agotamiento del pool celular de dNTP inhibiendo los pasos tempranos de la retrotranscripción en células infectadas; TREX1 que es considerado un factor de restricción del huésped antagónico ya que la ausencia del mismo resulta en la activación de una respuesta de interferón; APOBEC3 que media la restricción viral principalmente por un mecanismo de edición del DNA; TRIM5α que puede formar una estructura hexagonal por encima de la cápside, lo cual desestabilizaría el core viral; Tetherin que es capaz de bloquear la liberación de viriones de VIH.

  7. One hundred twenty years of koala retrovirus evolution determined from museum skins

    DEFF Research Database (Denmark)

    Avila Arcos, Maria del Carmen; Ho, Simon Y. W.; Ishida, Yasuko

    2013-01-01

    Although endogenous retroviruses are common across vertebrate genomes, the koala retrovirus (KoRV) is the only retrovirus known to be currently invading the germ line of its host. KoRV is believed to have first infected koalas in northern Australia less than two centuries ago. We examined Ko......RV in 28 koala museum skins collected in the late 19th and 20th centuries and deep sequenced the complete proviral envelope region from five northern Australian specimens. Strikingly, KoRV env sequences were conserved among koalas collected over the span of a century, and two functional motifs that affect...... viral infectivity were fixed across the museum koala specimens. We detected only 20 env polymorphisms among the koalas, likely representing derived mutations subject to purifying selection. Among northern Australian koalas, KoRV was already ubiquitous by the late 19th century, suggesting that Ko...

  8. Innate immune sensing of HIV-1 infection.

    Science.gov (United States)

    Jakobsen, Martin R; Olagnier, David; Hiscott, John

    2015-03-01

    The innate immune system plays a critical role in the control of viral infections. Although the mechanisms involved in sensing and response to viral pathogens has progressed tremendously in the last decade, an understanding of the innate antiviral response to human retroviruses lagged behind. Recent studies now demonstrate that human retroviruses such as human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus 1 (HTLV-1) trigger a type I interferon antiviral response through novel cytosolic sensors that detect DNA intermediates of reverse transcription; in addition, these early host-pathogen interactions may trigger cell death pathways depending on the activation state of the target cell. The purpose of this review is to summarize the recent progress in the understanding of innate immune sensing of human retroviruses. Innate immune sensing of HIV-1 and HTLV-1 is influenced by the target cell phenotype, viral replicative intermediates, and host restriction factors that limit retroviral replication. Macrophages and dendritic cells detect HIV-DNA intermediates, whereas CD4 T cells differentially sense HIV DNA depending on the level of T-cell activation. Furthermore, the structure of the viral capsid and interplay between innate DNA sensors and host restriction factors all contribute to the magnitude of the ensuing innate immune response. The interplay between HIV infection and the innate immune system has emerged as an important component of HIV pathogenesis, linked to both induction of innate immunity and stimulation of cell death mechanisms. Ultimately, an in-depth knowledge of the mechanisms of innate immune control of human retrovirus infection may facilitate the development of novel treatment strategies to control retrovirus-induced immunopathology.

  9. Heterogeneity of koala retrovirus isolates.

    Science.gov (United States)

    Shimode, Sayumi; Nakagawa, So; Yoshikawa, Rokusuke; Shojima, Takayuki; Miyazawa, Takayuki

    2014-01-03

    Koala retrovirus (KoRV) is a gammaretrovirus which may induce immune suppression, leukemia and lymphoma in koalas. Currently three KoRV subgroups (A, B, and J) have been reported. Our phylogenetic analysis suggests that KoRV-B and KoRV-J should be classified as the same subgroup. In long terminal repeat (LTR), a KoRV-B isolate has four 17 bp tandem repeats named direct repeat (DR)-1, while a KoRV-J isolate (strain OJ-4) has three 37 bp tandem repeats named DR-2. We also found that the promoter activity of the KoRV-J strain OJ-4 is stronger than that of original KoRV-A, suggesting that KoRV-J may replicate more efficiently than KoRV-A. Copyright © 2013. Published by Elsevier B.V.

  10. Oral Manifestations of Human Immunodeficiency Virus Infection

    OpenAIRE

    Epstein, Joel B.; Mathias, Richard G.

    1988-01-01

    The AIDS epidemic continues. All health-care workers, including physicians and dental personnel, may be instrumental in recognizing risk factors associated with Acquired Immunodeficiency Syndrome (AIDS) and Human Immunodeficiency Virus (HIV) infection. Oral signs and symptoms of HIV infection may be the first presentation of the disease or may develop during the course of the disease and require management. Knowledge of the signs, symptoms and associated infections and tumours is needed to as...

  11. Chlamydophila psittaci infection of birds and humans

    OpenAIRE

    Bülent Baş; Gökçen Dinç

    2015-01-01

    Psittacosis is a systemic infection with high morbidity caused by Chlamydophila psittaci in domestic and wild birds. It shows zoonotic characteristic. C. psittaci leads an infection in over of 470 bird species worldwide has been known. This is a fact that people have a close relationship both with wild and pet birds and this has paved the way for infection in humans of. C. psittaci Gram negative, obligate and intracellular bacterium with biphasic growth cycle. It is transmitted by respiratory...

  12. Lack of evidence for a role of T-cell-associated retroviruses as an etiology of schizophrenia.

    Science.gov (United States)

    Feenstra, A; Kirch, D G; Bracha, H S; Wyatt, R J

    1989-02-15

    The evidence that schizophrenia may involve infection by a virus (or viruses) has been indirect. The recent discovery, however, of the human retroviruses--human T-cell lymphoma-leukemia virus-I, and II (HTLV-I, -II) and human immunodeficiency virus (HIV)--now also known to affect the central nervous system (CNS), together with the development of new techniques in retrovirology, have made it possible to investigate more directly the role of this class of viruses as an etiology of schizophrenia. In our first effort to screen for the presence of a T-cell lymphotropic virus in schizophrenia, short-term tissue cultures of peripheral lymphocytes from 17 chronic schizophrenic patients and 10 normal controls were established. The cells were cultured in the presence of T-cell growth factor (TCGF, IL-2), and the culture supernatants were tested for the presence of the retroviral enzyme reverse transcriptase. No T-cell-associated reverse transcriptase activity was detected in cultures from patients or normal controls. Therefore, the data do not provide evidence for a role for T-cell lymphotropic retroviruses as an etiology of schizophrenia.

  13. Human Immunodeficiency Virus Infection among Psychiatric ...

    African Journals Online (AJOL)

    Background: Psychiatric patients are considered high risked group for Human immunodeficiency virus (HIV) infection. This has been found to be as a result of poor judgment and irrationality associated with some of the disorders. However, there is dearth of literature on the prevalence of HIV infection among psychiatric ...

  14. Construction and characterization of an infectious molecular clone of Koala retrovirus.

    Science.gov (United States)

    Shojima, Takayuki; Hoshino, Shigeki; Abe, Masumi; Yasuda, Jiro; Shogen, Hiroko; Kobayashi, Takeshi; Miyazawa, Takayuki

    2013-05-01

    Koala retrovirus (KoRV) is a gammaretrovirus that is currently endogenizing into koalas. Studies on KoRV infection have been hampered by the lack of a replication-competent molecular clone. In this study, we constructed an infectious molecular clone, termed plasmid pKoRV522, of a KoRV isolate (strain Aki) from a koala reared in a Japanese zoo. The virus KoRV522, derived from pKoRV522, grew efficiently in human embryonic kidney (HEK293T) cells, attaining 10(6) focus-forming units/ml. Several mutations in the Gag (L domain) and Env regions reported to be involved in reduction in viral infection/production in vitro are found in pKoRV522, yet KoRV522 replicated well, suggesting that any effects of these mutations are limited. Indeed, a reporter virus pseudotyped with pKoRV522 Env was found to infect human, feline, and mink cell lines efficiently. Analyses of KoRV L-domain mutants showed that an additional PPXY sequence, PPPY, in Gag plays a critical role in KoRV budding. Altogether, our results demonstrate the construction and characterization of the first infectious molecular clone of KoRV. The infectious clone reported here will be useful for elucidating the mechanism of endogenization of the virus in koalas and screening for antiretroviral drugs for KoRV-infected koalas.

  15. Unintended spread of a biosafety level 2 recombinant retrovirus

    Directory of Open Access Journals (Sweden)

    Liffers Sven-T

    2009-09-01

    Full Text Available Abstract Background Contamination of vertebrate cell lines with animal retroviruses has been documented repeatedly before. Although such viral contaminants can be easily identified with high sensitivity by PCR, it is impossible to screen for all potential contaminants. Therefore, we explored two novel methods to identify viral contaminations in cell lines without prior knowledge of the kind of contaminant. Results The first hint for the presence of contaminating retroviruses in one of our cell lines was obtained by electron microscopy of exosome-like vesicles released from the supernatants of transfected 293T cells. Random amplification of particle associated RNAs (PAN-PCR from supernatant of contaminated 293T cells and sequencing of the amplicons revealed several nucleotide sequences showing highest similarity to either murine leukemia virus (MuLV or squirrel monkey retrovirus (SMRV. Subsequent mass spectrometry analysis confirmed our findings, since we could identify several peptide sequences originating from monkey and murine retroviral proteins. Quantitative PCRs were established for both viruses to test currently cultured cell lines as well as liquid nitrogen frozen cell stocks. Gene fragments for both viruses could be detected in a broad range of permissive cell lines from multiple species. Furthermore, experimental infections of cells negative for these viruses showed that both viruses replicate rapidly to high loads. We decided to further analyze the genomic sequence of the MuLV-like contaminant virus. Surprisingly it was neither identical to MuLV nor to the novel xenotropic MuLV related retrovirus (XMRV but showed 99% identity to a synthetic retrovirus which was engineered in the 1980s. Conclusion The high degree of nucleotide identity suggests unintended spread of a biosafety level 2 recombinant virus, which could also affect the risk assessment of gene-modified organisms released from contaminated cell cultures. The study further

  16. Saffold virus infection associated with human myocarditis

    DEFF Research Database (Denmark)

    Nielsen, Trine Skov; Nielsen, Alex Yde; Banner, Jytte

    2016-01-01

    BACKGROUND: Saffold virus was described in 2007 as one of the first human viruses within the genus cardioviruses. Cardioviruses may cause severe infections of the myocardium in animals, and several studies have associated saffold virus with human disease. As a result, saffold virus has been...... in the myocardium, lung tissue and blood of one child and was accompanied by histopathological inflammation in the heart and lungs, which was supportive of a viral infection. These findings suggest that cardioviruses may be associated with myocarditis in humans....

  17. Can Helicobacter pylori infection influence human reproduction?

    Science.gov (United States)

    Moretti, Elena; Figura, Natale; Collodel, Giulia; Ponzetto, Antonio

    2014-05-21

    Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermatozoa, conceivably hampering the oocyte/sperm fusion. Infection by CagA positive organisms enhances the risk of preeclampsia, which is a main cause of foetus death. These findings are supported by the results of experimental infections of pregnant mice, which may cause reabsorption of a high number of foetuses and alter the balance between Th1 and Th2 cell response. Infected men have decreased sperm motility, viability and numbers of normally shaped sperm and augmented systemic levels of inflammatory cytokines, such as tumor necrosis factor-α, which may damage spermatozoa. In countries where parasitic infestation is endemic, detrimental effects of infection upon spermatozoa may not occur, because the immune response to parasites could determine a switch from a predominant Th1 type to Th2 type lymphocytes, with production of anti-inflammatory cytokines. In conclusion, the evidences gathered until now should be taken into consideration for future studies aiming to explore the possible role of H. pylori infection on human reproduction.

  18. Integration Site and Clonal Expansion in Human Chronic Retroviral Infection and Gene Therapy

    Science.gov (United States)

    Niederer, Heather A.; Bangham, Charles R. M.

    2014-01-01

    Retroviral vectors have been successfully used therapeutically to restore expression of genes in a range of single-gene diseases, including several primary immunodeficiency disorders. Although clinical trials have shown remarkable results, there have also been a number of severe adverse events involving malignant outgrowth of a transformed clonal population. This clonal expansion is influenced by the integration site profile of the viral integrase, the transgene expressed, and the effect of the viral promoters on the neighbouring host genome. Infection with the pathogenic human retrovirus HTLV-1 also causes clonal expansion of cells containing an integrated HTLV-1 provirus. Although the majority of HTLV-1-infected people remain asymptomatic, up to 5% develop an aggressive T cell malignancy. In this review we discuss recent findings on the role of the genomic integration site in determining the clonality and the potential for malignant transformation of cells carrying integrated HTLV-1 or gene therapy vectors, and how these results have contributed to the understanding of HTLV-1 pathogenesis and to improvements in gene therapy vector safety. PMID:25365582

  19. Oxygen tension level and human viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr [Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France); Université Denis Diderot, Sorbonne Paris Cité Paris, Paris (France); Casetti, Luana [Institut Cochin INSERM U1016, Paris (France); François, Jean-Hugues; Capron, Claude [Institut Cochin INSERM U1016, Paris (France); Laboratoire d' Hématologie, Hôpital Ambroise Paré, Boulogne (France); Université de Versailles Saint-Quentin en Yvelynes, Versailles (France); Pillet, Sylvie [Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France); Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon (France)

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  20. Human Infection in Wild Mountain Gorillas

    Centers for Disease Control (CDC) Podcasts

    2011-04-25

    This podcast discusses a study about the transmission of Human Metapneumovirus Infection to wild mountain gorillas in Rwanda in 2009, published in the April 2011 issue of Emerging Infectious Diseases. Dr. Ian Lipkin, Director of the Center for Infection and Immunity and Dr. Gustavo Palacios, investigator in the Center of Infection & Immunity share details of this study.  Created: 4/25/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 5/2/2011.

  1. B-lymphoblastoid cell lines from multiple sclerosis patients and a healthy control producing a putative new human retrovirus and Epstein-Barr virus

    DEFF Research Database (Denmark)

    Munch, M; Møller-Larsen, A; Christensen, T

    1995-01-01

    with MS who had a reactivated Epstein-Barr virus (EBV) infection. Both LCLs were found by EM to produce RVLP and EBV particles. Reverse transcriptase (RT) assays were positive in purified viral material from both LCLs. To substantiate these findings we initiated an intensified culturing procedure and were...

  2. Peptide inhibition of human cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Morris Cindy A

    2011-02-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB, a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS, several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF were infected with the Towne-GFP strain of HCMV (0.5 MOI, preincubated with peptides at a range of concentrations (78 nm to 100 μM, and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100

  3. Update on human Campylobacter jejuni infections.

    Science.gov (United States)

    Kirkpatrick, Beth D; Tribble, David R

    2011-01-01

    The present review will update the reader to the clinical, epidemiological and immunologic advances in the field of human campylobacteriosis. New advances in human campylobacteriosis include an increased appreciation of the role of Campylobacter jejuni in postinfectious sequelae, a broadened understanding of Campylobacter-associated disease burden and the interplay between host immunity and bacterial factors. Antibiotic management has also become more complex: C. jejuni has undergone a rapid increase in resistance to the fluoroquinolone antibiotics and concurrently, postinfectious irritable bowel syndrome has been associated with a longer duration of untreated infection. In anticipation of new candidate C. jejuni vaccines, progress in understanding human immune responses to infection has been made via human experimental infections. These tightly controlled studies have also increased our understanding of the natural history of campylobacteriosis as well as observations of recrudescent infection following treatment with C. jejuni-sensitive antibiotics. As one of the most common agents of bacterial gastroenteritis and a major health burden for both developing world and industrialized nations, Campylobacter infections remain a high priority for research efforts to improve prevention and management. Priorities for the future include vaccine development, pathogen-specific immunity and identification of risk factors for postinfectious sequelae.

  4. A Study of Brucella Infection in Humans

    Directory of Open Access Journals (Sweden)

    Hasanjani Roushan Mohammad Reza

    2014-07-01

    Full Text Available Objective: Brucellosis is the most usual zoonotic disease around the world especially in the Middle East, Mediterranean and Indian sub-continent areas. This bacterium has ten species that Brucella melitensis among them recognized as the most important cause of human brucellosis. This infection transfer ways to human include of wounds, bacteria inhalation and consumption of septic dairy such as raw milk, cream and butter. Brucellosis as a systemic disease can involve more organs of patients that have symptoms such as fever, night sweating, and backache. This infection can be divided as acute, sub-acute and chronic forms according to the manner of clinical presentation. Materials and Methods: This research is a review study and conducted by reviewing of the literature, which is related to this issue and also visiting, PubMed, and other linked websites. Results: In human brucellosis domestic animals are the main natural reservoir of infection. Whenever incidence rate of this infection in domestic and wild animals is reduced on the other hand incidence rate in human also will reduce. Conclusion: Blood cultures, serological tests and molecular tests are common laboratory methods of this infection. Diminution of relapse and therapeutic failure rates are as most important aim, which is researcher’s regards.

  5. Mycobacterium caprae infection in humans.

    Science.gov (United States)

    Prodinger, Wolfgang M; Indra, Alexandra; Koksalan, Orhan K; Kilicaslan, Zeki; Richter, Elvira

    2014-12-01

    Mycobacterium caprae, a member of the Mycobacterium tuberculosis complex, causes tuberculosis (TB) in man and animals. Some features distinguish M. caprae from its epidemiological twin, Mycobacterium bovis: M. caprae is evolutionarily older, accounts for a smaller burden of zoonotic TB and is not globally distributed, but primarily restricted to European countries. M. caprae occurs only in a low proportion of human TB cases and this proportion may even decrease, if progress toward eradication of animal TB in Europe continues. So why bother, if M. caprae is not an enigma for diagnostic TB tests and if resistance against first-line drugs is a rarity with M. caprae? This 'European' pathogen of zoonotic TB asks interesting questions regarding the definition of a species. The latter, seemingly only an academic question, particularly requires and challenges the collaboration between human and veterinary medicine.

  6. Porcine endogenous retrovirus-A/C: biochemical properties of its integrase and susceptibility to raltegravir.

    Science.gov (United States)

    Demange, Antonin; Yajjou-Hamalian, Halima; Gallay, Kathy; Luengo, Catherine; Beven, Véronique; Leroux, Aurélie; Confort, Marie-Pierre; Al Andary, Elsy; Gouet, Patrice; Moreau, Karen; Ronfort, Corinne; Blanchard, Yannick

    2015-10-01

    Porcine endogenous retroviruses (PERVs) are present in the genomes of pig cells. The PERV-A/C recombinant virus can infect human cells and is a major risk of zoonotic disease in the case of xenotransplantation of pig organs to humans. Raltegravir (RAL) is a viral integrase (IN) inhibitor used in highly active antiretroviral treatment. In the present study, we explored the potential use of RAL against PERV-A/C. We report (i) a three-dimensional model of the PERV-A/C intasome complexed with RAL, (ii) the sensitivity of PERV-A/C IN to RAL in vitro and (iii) the sensitivity of a PERV-A/C-IRES-GFP recombinant virus to RAL in cellulo. We demonstrated that RAL is a potent inhibitor against PERV-A/C IN and PERV-A/C replication with IC50s in the nanomolar range. To date, the use of retroviral inhibitors remains the only way to control the risk of zoonotic PERV infection during pig-to-human xenotransplantation.

  7. Protection against retrovirus pathogenesis by SR protein inhibitors.

    Directory of Open Access Journals (Sweden)

    Anne Keriel

    Full Text Available Indole derivatives compounds (IDC are a new class of splicing inhibitors that have a selective action on exonic splicing enhancers (ESE-dependent activity of individual serine-arginine-rich (SR proteins. Some of these molecules have been shown to compromise assembly of HIV infectious particles in cell cultures by interfering with the activity of the SR protein SF2/ASF and by subsequently suppressing production of splicing-dependent retroviral accessory proteins. For all replication-competent retroviruses, a limiting requirement for infection and pathogenesis is the expression of the envelope glycoprotein which strictly depends on the host splicing machinery. Here, we have evaluated the efficiency of IDC on an animal model of retroviral pathogenesis using a fully replication-competent retrovirus. In this model, all newborn mice infected with a fully replicative murine leukemia virus (MLV develop erythroleukemia within 6 to 8 weeks of age. We tested several IDC for their ability to interfere ex vivo with MLV splicing and virus spreading as well as for their protective effect in vivo. We show here that two of these IDC, IDC13 and IDC78, selectively altered splicing-dependent production of the retroviral envelope gene, thus inhibiting early viral replication in vivo, sufficiently to protect mice from MLV-induced pathogenesis. The apparent specificity and clinical safety observed here for both IDC13 and IDC78 strongly support further assessment of inhibitors of SR protein splicing factors as a new class of antiretroviral therapeutic agents.

  8. Cytomegalovirus infection presenting as acute periodontal infection in a patient infected with the human immunodeficiency virus.

    Science.gov (United States)

    Dodd, C L; Winkler, J R; Heinic, G S; Daniels, T E; Yee, K; Greenspan, D

    1993-04-01

    During childhood, many people acquire primary infection with cytomegalovirus (CMV), one of the herpes viruses. If they later become immunosuppressed, such as occurs with human immunodeficiency virus (HIV) infection, CMV is likely to become reactivated. Severe disease caused by CMV is life-threatening in the HIV-infected population. CMV retinitis, gastritis, colitis, pneumonia, encephalitis and hepatitis have all been reported, but oral lesions due to infection with CMV are rarely reported. We report a case of oral CMV infection which at first was clinically indistinguishable from HIV-associated periodontal disease.

  9. Atypical human infections by animal trypanosomes.

    Directory of Open Access Journals (Sweden)

    Philippe Truc

    Full Text Available The two classical forms of human trypanosomoses are sleeping sickness due to Trypanosoma brucei gambiense or T. brucei rhodesiense, and Chagas disease due to T. cruzi. However, a number of atypical human infections caused by other T. species (or sub-species have been reported, namely due to T. brucei brucei, T. vivax, T. congolense, T. evansi, T. lewisi, and T. lewisi-like. These cases are reviewed here. Some infections were transient in nature, while others required treatments that were successful in most cases, although two cases were fatal. A recent case of infection due to T. evansi was related to a lack of apolipoprotein L-I, but T. lewisi infections were not related to immunosuppression or specific human genetic profiles. Out of 19 patients, eight were confirmed between 1974 and 2010, thanks to improved molecular techniques. However, the number of cases of atypical human trypanosomoses might be underestimated. Thus, improvement, evaluation of new diagnostic tests, and field investigations are required for detection and confirmation of these atypical cases.

  10. Thrombocytopenia in Children Infected with the Human ...

    African Journals Online (AJOL)

    Background: Human immunodeficiency virus (HIV) infection is associated with a myriad of hematopoietic abnormalities, of which thrombocytopenia (TP) is a common complication. The condition could predispose to life-threatening hemorrhage. Objectives: To determine the prevalence of thrombocytopenia among HIV- ...

  11. Human Immunodeficiency Virus Infection Occupational Post ...

    African Journals Online (AJOL)

    opsig

    potentially infected body fluids so that they can present themselves rapidly for risk assessment and commencement of ART if necessary in the event of an occupational exposure to HIV. INTRODUCTION. Human Immunodeficiency Virus (HIV) is the virus that causes Acquired Immune Deficiency Syndrome. (AIDS). It can be ...

  12. Human immunodeficiency virus infection among migrant fishermen ...

    African Journals Online (AJOL)

    Background: People migrate from place to place for diverse reasons chief among which is economic. Migrant fishermen like other migrant population lead high risk sexual lifestyle and are therefore, predisposed to Human immunodeficiency virus (HIV) infection. Aim: To determine the prevalence of HIV among migrant ...

  13. Human Diphyllobothrium nihonkaiense Infection in Washington State

    Science.gov (United States)

    Billman, Zachary P.; Wallis, Carolyn K.; Abbott, April N.; Olson, John C.; Dhanireddy, Shireesha; Murphy, Sean C.

    2015-01-01

    A patient in Washington State harbored a fish tapeworm most likely acquired from eating raw salmon. Diphyllobothrium nihonkaiense was identified by cox1 sequence analysis. Although this is the first documented human D. nihonkaiense infection in the United States, the parasite may have been present earlier but misidentified as Diphyllobothrium latum. PMID:25609724

  14. HUMAN PAPILLOMAVIRUS INFECTIONS IN LARYNGEAL CANCER

    NARCIS (Netherlands)

    Torrente, Mariela C.; Rodrigo, Juan P.; Haigentz, Missak; Dikkers, Frederik G.; Rinaldo, Alessandra; Takes, Robert P.; Olofsson, Jan; Ferlito, Alfio

    Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we

  15. Cryptic diversity in hymenolepidid tapeworms infecting humans.

    Science.gov (United States)

    Nkouawa, Agathe; Haukisalmi, Voitto; Li, Tiaoying; Nakao, Minoru; Lavikainen, Antti; Chen, Xingwang; Henttonen, Heikki; Ito, Akira

    2016-04-01

    An adult hymenolepidid tapeworm was recovered from a 52-year-old Tibetan woman during a routine epidemiological survey for human taeniasis/cysticercosis in Sichuan, China. Phylogenetic analyses based on sequences of nuclear 28S ribosomal DNA and mitochondrial cytochrome c oxidase subunit 1 showed that the human isolate is distinct from Hymenolepis diminuta and Hymenolepis nana, the common parasites causing human hymenolepiasis. Proglottids of the human isolate were unfortunately unsuitable for morphological identification. However, the resultant phylogeny demonstrated the human isolate to be a sister species to Hymenolepis hibernia from Apodemus mice in Eurasia. The present data clearly indicate that hymenolepidid tapeworms causing human infections are not restricted to only H. diminuta and H. nana. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Directed DNA shuffling of retrovirus and retrotransposon integrase protein domains.

    Directory of Open Access Journals (Sweden)

    Xiaojie Qi

    Full Text Available Chimeric proteins are used to study protein domain functions and to recombine protein domains for novel or optimal functions. We used a library of chimeric integrase proteins to study DNA integration specificity. The library was constructed using a directed shuffling method that we adapted from fusion PCR. This method easily and accurately shuffles multiple DNA gene sequences simultaneously at specific base-pair positions, such as protein domain boundaries. It produced all 27 properly-ordered combinations of the amino-terminal, catalytic core, and carboxyl-terminal domains of the integrase gene from human immunodeficiency virus, prototype foamy virus, and Saccharomyces cerevisiae retrotransposon Ty3. Retrotransposons can display dramatic position-specific integration specificity compared to retroviruses. The yeast retrotransposon Ty3 integrase interacts with RNA polymerase III transcription factors to target integration at the transcription initiation site. In vitro assays of the native and chimeric proteins showed that human immunodeficiency virus integrase was active with heterologous substrates, whereas prototype foamy virus and Ty3 integrases were not. This observation was consistent with a lower substrate specificity for human immunodeficiency virus integrase than for other retrovirus integrases. All eight chimeras containing the Ty3 integrase carboxyl-terminal domain, a candidate targeting domain, failed to target strand transfer in the presence of the targeting protein, suggesting that multiple domains of the Ty3 integrase cooperate in this function.

  17. Human papilloma virus infection and psoriasis: Did human papilloma virus infection trigger psoriasis?

    Science.gov (United States)

    Jain, Sonia P; Gulhane, Sachin; Pandey, Neha; Bisne, Esha

    2015-01-01

    Psoriasis is an autoimmune chronic inflammatory skin disease known to be triggered by streptococcal and HIV infections. However, human papilloma virus infection (HPV) as a triggering factor for the development of psoriasis has not been reported yet. We, hereby report a case of plaque type with inverse psoriasis which probably could have been triggered by genital warts (HPV infection) and discuss the possible pathomechanisms for their coexistence and its management.

  18. Virus infection and human cancer: an overview.

    Science.gov (United States)

    Schiller, John T; Lowy, Douglas R

    2014-01-01

    It is now estimated that approximately 10 % of worldwide cancers are attributable to viral infection, with the vast majority (>85 %) occurring in the developing world. Oncogenic viruses include various classes of DNA and RNA viruses and induce cancer by a variety of mechanisms. A unifying theme is that cancer develops in a minority of infected individuals and only after chronic infection of many years duration. The viruses associated with the greatest number of cancer cases are the human papillomaviruses (HPVs), which cause cervical cancer and several other epithelial malignancies, and the hepatitis viruses HBV and HCV, which are responsible for the majority of hepatocellular cancer. Other oncoviruses include Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). Identification of the infectious cause has led to several interventions that may reduce the risk of developing these tumors. These include preventive vaccines against HBV and HPV, HPV-based testing for cervical cancer screening, anti-virals for the treatment of chronic HBV and HCV infection, and screening the blood supply for the presence of HBV and HCV. Successful efforts to identify additional oncogenic viruses in human cancer may lead to further insight into etiology and pathogenesis as well as to new approaches for therapeutic and prophylactic intervention.

  19. The xenotropic murine leukemia virus-related retrovirus debate continues at first international workshop

    NARCIS (Netherlands)

    J.P. Stoye (Jonathan); R.H. Silverman (Robert); C.A.B. Boucher (Charles); S.F.J. Le Grice

    2010-01-01

    textabstractThe 1stInternational Workshop on Xenotropic Murine Leukemia Virus-Related Retrovirus (XMRV), co-sponsored by the National Institutes of Health, The Department of Health and Human Services and Abbott Diagnostics, was convened on September 7/8, 2010 on the NIH campus, Bethesda, MD.

  20. Rhinovirus genome evolution during experimental human infection.

    Directory of Open Access Journals (Sweden)

    Samuel Cordey

    Full Text Available Human rhinoviruses (HRVs evolve rapidly due in part to their error-prone RNA polymerase. Knowledge of the diversity of HRV populations emerging during the course of a natural infection is essential and represents a basis for the design of future potential vaccines and antiviral drugs. To evaluate HRV evolution in humans, nasal wash samples were collected daily for five days from 15 immunocompetent volunteers experimentally infected with a reference stock of HRV-39. In parallel, HeLa-OH cells were inoculated to compare HRV evolution in vitro. Nasal wash in vivo assessed by real-time PCR showed a viral load that peaked at 48-72 h. Ultra-deep sequencing was used to compare the low-frequency mutation populations present in the HRV-39 inoculum in two human subjects and one HeLa-OH supernatant collected 5 days post-infection. The analysis revealed hypervariable mutation locations in VP2, VP3, VP1, 2C and 3C genes and conserved regions in VP4, 2A, 2B, 3A, 3B and 3D genes. These results were confirmed by classical sequencing of additional samples, both from inoculated volunteers and independent cell infections, and suggest that HRV inter-host transmission is not associated with a strong bottleneck effect. A specific analysis of the VP1 capsid gene of 15 human cases confirmed the high mutation incidence in this capsid region, but not in the antiviral drug-binding pocket. We could also estimate a mutation frequency in vivo of 3.4x10(-4 mutations/nucleotides and 3.1x10(-4 over the entire ORF and VP1 gene, respectively. In vivo, HRV generate new variants rapidly during the course of an acute infection due to mutations that accumulate in hot spot regions located at the capsid level, as well as in 2C and 3C genes.

  1. [Efficient packaging retrovirus and construction of transgenic chicken technical platform].

    Science.gov (United States)

    Man, Chaolai; Zhang, Qing; Chen, Yan; Zhu, Dahai

    2007-10-01

    Transgenic chicken and oviduct bioreactor are growing to be one of the hotspot of scientific study in the field of biology. The most successful method of producing transgenic chicken is pseudotyped retrovirus vector system, but no one has reported the production of transgenic chicken by retrovirus system recently in our country. In order to accelerate our study in this field, we introduced the relevant technical methods such as packaging retrovirus and vesicular stomatitis virus G glycoprotein (VSV-G) pseudotyped retrovirus, optimizing the conditions of packaging retrovirus, concentrating VSV-G pseudotyped retrovirus, helper virus assays, and microinjection of retrovirus. Furthermore, we successfully conducted in vivo study for detecting the marker gene EGFP of chicken embryo as well as in vitro study for detecting that gene of chicken embryo myoblast (CFM), thus we have provided an applied technical platform for studies of transgenic chicken in the future.

  2. Epidemiological aspects of retrovirus (HTLV infection among Indian populations in the Amazon Region of Brazil Aspectos epidemiológicos da infecção pelo retrovírus HTLV entre populações indígenas da Amazônia brasileira

    Directory of Open Access Journals (Sweden)

    Ricardo Ishak

    2003-08-01

    Full Text Available HTLV was initially described in association with a form of leukemia in Japan and a neurological disease in the Caribbean. It was soon shown that HTLV-II was endemic among Amerindians and particularly among Brazilian Indians. The Amazon Region of Brazil is presently the largest endemic area for this virus and has allowed several studies concerning virus biology, the search for overt disease, epidemiological data including detailed demographic data on infected individuals, clear-cut geographic distribution, definition of modes of transmission and maintenance within small, epidemiologically-closed groups, and advances in laboratory diagnosis of the infection. A new molecular subtype named HTLV-IIc was further described on the basis of genome sequencing and phylogenetic analysis. This subtype is present in other areas of Brazil, indicating that the virus is additionally both a valuable marker for tracing past human migration routes in the Americas and a probable marker for social habits of the present human population. HIV, the other human retrovirus, is still not prevalent among indigenous communities in the Brazilian Amazon, but these groups are also easy targets for the virus.O HTLV foi descrito inicialmente associado a uma leucemia no Japão e a uma doença neurológica presente no Caribe. Logo foi evidenciado que o HTLV-II era endêmico entre Ameríndios e, particularmente, entre Índios brasileiros. A Amazônia brasileira é a maior área endêmica para o vírus e dessa forma, permitiu que fossem realizados vários estudos relacionados com a sua biologia, a busca de doença, informações epidemiológicas que incluíram uma bem definida distribuição geográfica, a definição dos modos de transmissão e manutenção do vírus em comunidades pequenas, epidemiologicamente fechadas, assim como contribuições para o diagnóstico laboratorial da infecção. Um novo subtipo molecular, denominado HTLV-IIc, foi adicionalmente descrito baseando

  3. endogenous retrovirus sequences expressed in male mammalian

    African Journals Online (AJOL)

    2002-01-02

    Jan 2, 2002 ... demonstrated in New Zealand Black mice, where the reproductive tract of males were shown to contain C-type retrovirus(35). Also endogenous mouse mammary tumour virus (MMTV) proteins (p28 and gp47) have been identified in the epididymis and seminal vesicles of adult Swiss. Albino mice devoid of ...

  4. Infections caused by Kluyvera species in humans.

    Science.gov (United States)

    Sarria, J C; Vidal, A M; Kimbrough, R C

    2001-10-01

    Kluyvera is a relatively newly described genus in the family Enterobacteriaceae that infrequently causes infections in humans. The organism has been isolated from various clinical specimens, but its significance has not been clearly established. In fact, it has been regarded alternatively as saprophytic, opportunistic, or pathogenic. Since the redefinition of this genus in 1981, case reports of diverse clinical infections occurring under various host conditions have been published. Here we present a critical review of all Kluyvera infections reported in the literature, along with our experience involving 5 additional cases. Most patients received prompt antimicrobial treatment on the basis of susceptibility testing, and overall the clinical outcomes were good. Antimicrobial agents active against most Kluyvera strains include third-generation cephalosporins, fluoroquinolones, and aminoglycosides. In contrast, the resistance to ampicillin, extended-spectrum penicillins, and first- and second-generation cephalosporins is significant. Kluyvera is a potentially virulent pathogen that deserves aggressive treatment designed with an awareness of the organism's antimicrobial resistance patterns.

  5. HUMAN PARASITIC INFECTIONS IN BALI : A REVIEW

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    Putu Sutisna

    2012-09-01

    Full Text Available Parasitic infections in humans in Bali are well documented, especially in the population who lived in rural areas. The most common infections are those of the soil-transmitted helminthiasis which are caused by Ascaris lumbricoides, Trichuris trichiura and hookworm showing prevalence rates of 40 - 95%, 25 - 90% and 20 - 70% respectively. Enterobius vermicularis prevalence rate has been reported to be 18 - 53%. Taenniasis prevalence rate has been documented to be 0.8 - 23% in some villages, where Taenia saginata was found to be more prevalent than Taenia solium, and this might be due to the eating habit of the Balinese people who consumed both pork and beef lawar. Malaria is still found in Bali especially in regions along the coasts of some regencies, although generally the infection rate is low. The prevalence rates of intestinal protozoa such as Giardia lamblia, Entamoeba histolytica, Balantidium coli have been occasionally reported in low percentages.

  6. The Retrovirus pol Gene Encodes a Product Required for DNA Integration: Identification of a Retrovirus int Locus

    Science.gov (United States)

    Panganiban, Antonito T.; Temin, Howard M.

    1984-12-01

    We mutagenized cloned spleen necrosis virus DNA to identify a region of the retrovirus genome encoding a polypeptide required for integration of viral DNA. Five plasmids bearing different lesions in the 3' end of the pol gene were examined for the ability to integrate or replicate following transfection of chicken embryo fibroblasts. Transfection with one of these DNAs resulted in the generation of mutant virus incapable of integrating but able to replicate at low levels; this phenotype is identical to that of mutants bearing alterations in the cis-acting region, att. To determine whether the 3' end of the pol gene encodes a protein that interacts with att, we did a complementation experiment. Cells were first infected with an att- virus and then superinfected with the integration-deficient virus containing a lesion in the pol gene and a wild-type att site. The results showed that the att- virus provided a trans-acting function allowing integration of viral DNA derived from the mutant bearing a wild-type att site. Thus, the 3' end of the pol gene serves as an ``int'' locus and encodes a protein mediating integration of retrovirus DNA through interaction with att.

  7. Human Schistosome Infection and Allergic Sensitisation

    Directory of Open Access Journals (Sweden)

    Nadine Rujeni

    2012-01-01

    Full Text Available Several field studies have reported an inverse relationship between the prevalence of helminth infections and that of allergic sensitisation/atopy. Recent studies show that immune responses induced by helminth parasites are, to an extent, comparable to allergic sensitisation. However, helminth products induce regulatory responses capable of inhibiting not only antiparasite immune responses, but also allergic sensitisation. The relative effects of this immunomodulation on the development of protective schistosome-specific responses in humans has yet to be demonstrated at population level, and the clinical significance of immunomodulation of allergic disease is still controversial. Nonetheless, similarities in immune responses against helminths and allergens pose interesting mechanistic and evolutionary questions. This paper examines the epidemiology, biology and immunology of allergic sensitisation/atopy, and schistosome infection in human populations.

  8. [Human papillomavirus infection in male genitalia].

    Science.gov (United States)

    Cano Garfias, R; Villarreal Peral, C; Juárez Azpilcueta, A

    1995-10-01

    A prospective and transversal study in 100 patients since January to December of 1994, was done, to know the human papiloma virus infection prevalence in male genitals. The patients were studied by a clinical history, genital area colposcopic revision after acetic acid 5% application, biopsy of the lesion and histopathology study. The patients age was among 16 to 71 years old, with a media of 38.8 years old. The sexual activity beginning was from 12 to 27 years old, with an average of 18 years old. Forty one percent of the patients have had sexual relations with prostitutes, 26% have had sexually transmitted diseases, 9% of the patients referred only 1 sexual mate and 82% had human papiloma virus infection.

  9. Leishmania major infection in humanized mice induces systemic infection and provokes a nonprotective human immune response.

    Directory of Open Access Journals (Sweden)

    Anja Kathrin Wege

    Full Text Available BACKGROUND: Leishmania (L. species are the causative agent of leishmaniasis. Due to the lack of efficient vaccine candidates, drug therapies are the only option to deal with cutaneous leishmaniasis. Unfortunately, chemotherapeutic interventions show high toxicity in addition to an increased risk of dissemination of drug-resistant parasites. An appropriate laboratory animal based model is still missing which allows testing of new drug strategies in the context of human immune cells in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Humanized mice were infected subcutaneously with stationary phase promastigote L. major into the footpad. The human immune response against the pathogen and the parasite host interactions were analyzed. In addition we proved the versatility of this new model to conduct drug research studies by the inclusion of orally given Miltefosine. We show that inflammatory human macrophages get infected with Leishmania parasites at the site of infection. Furthermore, a Leishmania-specific human-derived T cell response is initiated. However, the human immune system is not able to prevent systemic infection. Thus, we treated the mice with Miltefosine to reduce the parasitic load. Notably, this chemotherapy resulted in a reduction of the parasite load in distinct organs. Comparable to some Miltefosine treated patients, humanized mice developed severe side effects, which are not detectable in the classical murine model of experimental leishmaniasis. CONCLUSIONS/SIGNIFICANCE: This study describes for the first time L. major infection in humanized mice, characterizes the disease development, the induction of human adaptive and innate immune response including cytokine production and the efficiency of Miltefosine treatment in these animals. In summary, humanized mice might be beneficial for future preclinical chemotherapeutic studies in systemic (visceral leishmaniasis allowing the investigation of human immune response, side effects of the drug

  10. Human alpha-defensins block papillomavirus infection.

    Science.gov (United States)

    Buck, Christopher B; Day, Patricia M; Thompson, Cynthia D; Lubkowski, Jacek; Lu, Wuyuan; Lowy, Douglas R; Schiller, John T

    2006-01-31

    Sexually transmitted human papillomaviruses (HPVs) are the primary cause of cervical cancer. Recent advances in techniques for production of papillomaviral vectors [known as pseudoviruses (PsVs)] have made it possible to perform high-throughput screens for compounds that might block the initial stages of papillomavirus infection. We have used PsVs to screen a variety of compounds that might function as inhibitors of HPV infection, with emphasis on human peptides previously implicated in innate antimicrobial immunity. Little is known about the possible activity of these peptides against nonenveloped viruses, such as HPVs. Our screen revealed that human alpha-defensins 1-3 [known as human neutrophil peptides (HNPs) 1-3] and human alpha-defensin 5 (HD-5) are potent antagonists of infection by both cutaneous and mucosal papillomavirus types. In contrast, human beta-defensins 1 and 2 displayed little or no anti-HPV activity. HD-5 was particularly active against sexually transmitted HPV types, with 50% inhibitory doses in the high ng/ml range. Microscopic studies of PsV inhibition by the alpha-defensins revealed that they block virion escape from endocytic vesicles but not virion binding or internalization. Consistent with this finding, PsVs remained susceptible to inhibition by alpha-defensins for many hours after initial binding to cells. HNPs 1-3 and HD-5 have been reported to be present in the female genital tract at levels that overlap those that inhibit HPVs in vitro, suggesting that they could present a natural barrier to the sexual transmission of HPV and could serve as the basis of a broad-spectrum topical microbicide.

  11. Epidemiology of virus infection and human cancer.

    Science.gov (United States)

    Chen, Chien-Jen; Hsu, Wan-Lun; Yang, Hwai-I; Lee, Mei-Hsuan; Chen, Hui-Chi; Chien, Yin-Chu; You, San-Lin

    2014-01-01

    The International Agency for Research on Cancer (IARC) has comprehensively assessed the human carcinogenicity of biological agents. Seven viruses including Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Kaposi's sarcoma herpes virus (KSHV), human immunodeficiency virus, type-1 (HIV-1), human T cell lymphotrophic virus, type-1 (HTLV-1), and human papillomavirus (HPV) have been classified as Group 1 human carcinogens by IARC. The conclusions are based on the findings of epidemiological and mechanistic studies. EBV, HPV, HTLV-1, and KSHV are direct carcinogens; HBV and HCV are indirect carcinogens through chronic inflammation; HIV-1 is an indirect carcinogen through immune suppression. Some viruses may cause more than one cancer, while some cancers may be caused by more than one virus. However, only a proportion of persons infected by these oncogenic viruses will develop specific cancers. A series of studies have been carried out to assess the viral, host, and environmental cofactors of EBV-associated nasopharyngeal carcinoma, HBV/HCV-associated hepatocellular carcinoma, and HPV-associated cervical carcinoma. Persistent infection and high viral load are important risk predictors of these virus-caused cancers. Risk calculators incorporating host and viral factors have also been developed for the prediction of long-term risk of hepatocellular carcinoma. These risk calculators are useful for the triage and clinical management of infected patients. Both clinical trials and national programs of immunization or antiviral therapy have demonstrated a significant reduction in the incidence of cancers caused by HBV, HCV, and HPV. Future researches on gene-gene and gene-environment interaction of oncogenic viruses and human host are in urgent need.

  12. Increased titers of neutralizing antibodies after immunization with both envelope proteins of the porcine endogenous retroviruses (PERVs

    Directory of Open Access Journals (Sweden)

    Denner Joachim

    2012-11-01

    Full Text Available Abstract Despite enormous difficulties to induce antibodies neutralizing HIV-1, especially broadly neutralizing antibodies directed against the conserved membrane proximal external region (MPER of the transmembrane envelope protein, such antibodies can be easily induced in the case of gammaretroviruses, among them the porcine endogenous retroviruses (PERVs. In addition to neutralizing antibodies directed against the transmembrane envelope protein p15E, neutralizing antibodies were also induced by immunization with the surface envelope protein gp70. PERVs represent a special risk for xenotransplantation using pig tissues or organs since they are integrated in the genome of all pigs and infect human cells and a vaccine may protect from transmission to the recipient. To investigate the effect of simultaneous immunization with both proteins in detail, a study was performed in hamsters. Gp70 and p15E of PERV were produced in E. coli, purified and used for immunization. All animals developed binding antibodies against the antigens used for immunization. Sera from animals immunized with p15E recognized epitopes in the MPER and the fusion peptide proximal region (FPPR of p15E. One MPER epitope showed a sequence homology to an epitope in the MPER of gp41 of HIV-1 recognized by broadly neutralizing antibodies found in HIV infected individuals. Neutralizing antibodies were detected in all sera. Most importantly, sera from animals immunized with gp70 had a higher neutralizing activity when compared with the sera from animals immunized with p15E and sera from animals immunized with gp70 together with p15E had a higher neutralizing activity compared with sera from animals immunized with each antigen alone. These immunization studies are important for the development of vaccines against other retroviruses including the human immunodeficiency virus HIV-1.

  13. Human Respiratory Syncytial Virus: Infection and Pathology.

    Science.gov (United States)

    Bohmwald, Karen; Espinoza, Janyra A; Rey-Jurado, Emma; Gómez, Roberto S; González, Pablo A; Bueno, Susan M; Riedel, Claudia A; Kalergis, Alexis M

    2016-08-01

    The human respiratory syncytial virus (hRSV) is by far the major cause of acute lower respiratory tract infections (ALRTIs) worldwide in infants and children younger than 2 years. The overwhelming number of hospitalizations due to hRSV-induced ALRTI each year is due, at least in part, to the lack of licensed vaccines against this virus. Thus, hRSV infection is considered a major public health problem and economic burden in most countries. The lung pathology developed in hRSV-infected individuals is characterized by an exacerbated proinflammatory and unbalanced Th2-type immune response. In addition to the adverse effects in airway tissues, hRSV infection can also cause neurologic manifestations in the host, such as seizures and encephalopathy. Although the origins of these extrapulmonary symptoms remain unclear, studies with patients suffering from neurological alterations suggest an involvement of the inflammatory response against hRSV. Furthermore, hRSV has evolved numerous mechanisms to modulate and evade the immune response in the host. Several studies have focused on elucidating the interactions between hRSV virulence factors and the host immune system, to rationally design new vaccines and therapies against this virus. Here, we discuss about the infection, pathology, and immune response triggered by hRSV in the host. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. Human Cytomegalovirus Manipulation of Latently Infected Cells

    Science.gov (United States)

    Sinclair, John H.; Reeves, Matthew B.

    2013-01-01

    Primary infection with human cytomegalovirus (HCMV) results in the establishment of a lifelong infection of the host which is aided by the ability of HCMV to undergo a latent infection. One site of HCMV latency in vivo is in haematopoietic progenitor cells, resident in the bone marrow, with genome carriage and reactivation being restricted to the cells of the myeloid lineage. Until recently, HCMV latency has been considered to be relatively quiescent with the virus being maintained essentially as a “silent partner” until conditions are met that trigger reactivation. However, advances in techniques to study global changes in gene expression have begun to show that HCMV latency is a highly active process which involves expression of specific latency-associated viral gene products which orchestrate major changes in the latently infected cell. These changes are argued to help maintain latent infection and to modulate the cellular environment to the benefit of latent virus. In this review, we will discuss these new findings and how they impact not only on our understanding of the biology of HCMV latency but also how they could provide tantalising glimpses into mechanisms that could become targets for the clearance of latent HCMV. PMID:24284875

  15. Experimental Campylobacter Jejuni Infection in Humans

    Science.gov (United States)

    1988-03-01

    Blaser MJI Black RE. Duncan DJ, Amer I. Campylobacter Clements ML, Robins-Brone R, Lim Y-L. Duration of jejuni -specific serum antibodies are elevated in...SUBTITLE 5 FUNDING •4UMBERS Experimental Campylobacter jejuni Infection 86PP6826 in Humans 61102A 30161102BS13 AB6. AUTHOR(S)DA328 Robert E. Black...SUPPLEMENTARY NOTES Contract Title: Studies of the Outer Membrane Proteins of Campylobacter Jejuni for Vaccine Development ൔa• DISTRIBUTION

  16. [Ecology and social organization of African tropical forest primates: aid in understanding retrovirus transmission].

    Science.gov (United States)

    Tutin, C E

    2000-07-01

    The risk of transmission of primate viruses to humans is great because of their genetic proximity. It is now clear that the HIV group of retroviruses came from primates and that the origin of HIV1 is the chimpanzee subspecies of Central Africa, Pan troglodytes troglodytes. Many African primates are natural hosts of retroviruses and details of the natural history of both hosts and viruses are essential to understand the evolution of the latter. Data on the demography, ecology and behaviour of three species of primates (gorillas, chimpanzees and mandrills), studied in the Lopé Reserve in Central Gabon since 1983, are analysed to identify the factors that allow, or favour, disease transmission within each species, between different species and between primates and humans. The comparison of the relative degree of risk suggests that of the three species, chimpanzees are the most susceptible to exposure to infection both from conspecifics and from other species. With respect to humans, the comparative analysis suggests greater exposure to viruses of mandrills and gorillas than to those of chimpanzees. For primates, major risk factors are: large social groups; bites inflicted in fights; social grooming; and predation on mammals. However, given that contacts between social groups of the same species are rare, the spread of a virus through a population will be slow and uncertain. Hunting wild animals is the behaviour most likely to provide transmission routes for primate viruses into human populations because of the high probability of blood-blood contact. Not only the hunters themselves, but also women who prepare bush meat for cooking and people involved in trade of carcasses are at high risk of transmission of pathogens. Hunting of bush meat is increasing in Central Africa due to the economic recession and the spread of logging into the forests of the interior of the region. To counter the significant risk of transmission of known, as well as new, diseases from primates

  17. Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Brudek, Tomasz; Christensen, Tove; Hansen, Hans Jacob

    2008-01-01

    Human endogenous retroviruses (HERV) and herpesviruses are increasingly associated with the pathogenesis of the neurological inflammatory disease multiple sclerosis (MS). Herpesviruses are capable of HERV activation and simultaneous presence of HERV and herpesvirus antigens have a synergistic...

  18. Establishment of cell strains stably-transfected with luciferase gene mediated by retrovirus and their detection with bioluminescence imaging system

    Directory of Open Access Journals (Sweden)

    Hai-juan WANG

    2012-05-01

    Full Text Available Objective  To establish cell strains stably transfected with Luciferase gene (Luc2, which was mediated by retrovirus, and explore the relationship between the number of Luc2-positive cells and light flux from bioluminescence imaging system by experiments in vitro and in vivo. Methods  We co-transfected pMX-Luc2 plasmid and pMD.G plasmid into 293T gag-pol cells to get retrovirus expressing Luc2 gene. Stable Luc2 positive cell lines were generated and screened by transduction of Retro-Luc2 in mouse colon cancer cell line CT26, human non-small cell lung cancer cell line NCI-H446, human colon cancer cell line HT-29, human ovarian carcinoma cell line SKOV3 and human hepatocellular carcinoma cell line SMMC-7721, all of them were identified by bioluminescence imaging system. Different numbers of SKOV3-Luc2 cells ranging from 10 to 10000 were plated onto culture dishes. Two xenograft models of ovarian cancer were reproduced by subcutaneous injection of 200μl SKOV3-Luc2 cell suspension with different concentrations (1×107, 5×106, 2.5×106, 1×106, 5×105, 2.5×105, 1×105 and 5×104/ml into 16 sites on the back of 4 nude mice, or intravenous injection of 1×106 or 3 ×106 SKOV3-Luc2 cells into the tail vein. Light flux value of SKOV3-Luc2 cells in dishes and in mice was measured by bioluminescence imaging system. Results  Retro-Luc2 was constructed successfully and expressed Luc2 stably in transduced CT26, NCI-H446, HT-29, SKOV3 and SMMC-7721 cell lines. Light flux was correlated in a linear manner with the number of Luc2-positive cells in dishes and in mice (R2=0.944, β=0.972; R2=0.991, β=0.996; R2=0.351, β=0.628; P < 0.01. Conclusion  Luc2-positive cell lines could be established rapidly and accurately by infecting tumor cells with retrovirus expressing Luc2. The number of Luc2 positive cells is significantly related in a linear manner to light flux from bioluminescence imaging system in vitro and in vivo.

  19. Reassessment of murine APOBEC1 as a retrovirus restriction factor in vivo.

    Science.gov (United States)

    Barrett, Bradley S; Guo, Kejun; Harper, Michael S; Li, Sam X; Heilman, Karl J; Davidson, Nicholas O; Santiago, Mario L

    2014-11-01

    APOBEC1 is a cytidine deaminase involved in cholesterol metabolism that has been linked to retrovirus restriction, analogous to the evolutionarily-related APOBEC3 proteins. In particular, murine APOBEC1 was shown to inhibit Friend retrovirus (FV) in vitro, generating high levels of C-to-T and G-to-A mutations. These observations raised the possibility that FV infection might be altered in APOBEC1-null mice. To examine this question directly, we infected wild-type and APOBEC1-null mice with FV complex and evaluated acute infection levels. Surprisingly, APOBEC1-null mice exhibited similar cellular infection levels and plasma viremia relative to wild-type mice. Moreover, next-generation sequencing analyses revealed that in contrast to APOBEC3, APOBEC1 did not enhance retroviral C-to-T and G-to-A mutational frequencies in genomic DNA. Thus, APOBEC1 neither inhibited nor significantly drove the molecular evolution of FV in vivo. Our findings reinforce that not all retrovirus restriction factors characterized as potent in vitro may be functionally relevant in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Endogenous retrovirus and radiation-induced leukemia in the RMF mouse

    Energy Technology Data Exchange (ETDEWEB)

    Tennant, R.W.; Boone, L.R.; Lalley, P.; Yang, W.K.

    1982-01-01

    The induction of myeloid leukemia in irradiated RFM/Un mice has been associated with retrovirus infection. However, two characteristics of this strain complicate efforts to define the role of the virus. This strain possesses only one inducible host range class of endogenous virus and a unique gene, in addition to the Fv-1/sup n/ locus, which specifically restricts exogenous infection by endogenous viruses. These characteristics possibly account for absence of recombinant viruses in this strain, even though virus is amply expressed during most of the animal's life span. We have examined further the distribution of retrovirus sequences and the chromosomal locus of the inducible virus in this strain. This report describes evidence for additional viral sequences in cells of a radiation-induced myeloid leukemia line and discusses the possible origin of these added copies.

  1. The National Heart, Lung, and Blood Institute retrovirus epidemiology donor studies (Retrovirus Epidemiology Donor Study and Retrovirus Epidemiology Donor Study-II): twenty years of research to advance blood product safety and availability.

    Science.gov (United States)

    Kleinman, Steven; King, Melissa R; Busch, Michael P; Murphy, Edward L; Glynn, Simone A

    2012-10-01

    The Retrovirus Epidemiology Donor Study (REDS), conducted from 1989 to 2001, and the REDS-II, conducted from 2004 to 2012, were National Heart, Lung, and Blood Institute-funded, multicenter programs focused on improving blood safety and availability in the United States. The REDS-II also included international study sites in Brazil and China. The 3 major research domains of REDS/REDS-II have been infectious disease risk evaluation, blood donation availability, and blood donor characterization. Both programs have made significant contributions to transfusion medicine research methodology by the use of mathematical modeling, large-scale donor surveys, innovative methods of repository sample storage, and establishing an infrastructure that responded to potential emerging blood safety threats such as xenotropic murine leukemia virus-related virus. Blood safety studies have included protocols evaluating epidemiologic and/or laboratory aspects of human immunodeficiency virus, human T-lymphotropic virus 1/2, hepatitis C virus, hepatitis B virus, West Nile virus, cytomegalovirus, human herpesvirus 8, parvovirus B19, malaria, Creutzfeldt-Jakob disease, influenza, and Trypanosoma cruzi infections. Other analyses have characterized blood donor demographics, motivations to donate, factors influencing donor return, behavioral risk factors, donors' perception of the blood donation screening process, and aspects of donor deferral. In REDS-II, 2 large-scale blood donor protocols examined iron deficiency in donors and the prevalence of leukocyte antibodies. This review describes the major study results from over 150 peer-reviewed articles published by these 2 REDS programs. In 2011, a new 7-year program, the Recipient Epidemiology and Donor Evaluation Study-III, was launched. The Recipient Epidemiology and Donor Evaluation Study-III expands beyond donor-based research to include studies of blood transfusion recipients in the hospital setting and adds a third country, South Africa

  2. Simultaneous RNA quantification of human and retroviral genomes reveals intact interferon signaling in HTLV-1-infected CD4+ T cell lines

    Directory of Open Access Journals (Sweden)

    Moens Britta

    2012-08-01

    Full Text Available Abstract Background IFN-α contributes extensively to host immune response upon viral infection through antiviral, pro-apoptotic, antiproliferative and immunomodulatory activities. Although extensively documented in various types of human cancers and viral infections, controversy exists in the exact mechanism of action of IFN-α in human immunodeficiency virus type 1 (HIV-1 and human T-lymphotropic virus type 1 (HTLV-1 retroviral infections. Results IFN-α displayed strong anti-HIV-1 effects in HIV-1/HTLV-1 co-infected MT-4 cells in vitro, demonstrated by the dose-dependent inhibition of the HIV-1-induced cytopathic effect (IC50 = 83.5 IU/ml, p 50 = 1.2 IU/ml, p  Conclusions Taken together, our results indicate that both the absence of in vitro antiproliferative and pro-apoptotic activity as well as the modest post-transcriptional antiviral activity of IFN-α against HTLV-1, were not due to a cell-intrinsic defect in IFN-α signalisation, but rather represents a retrovirus-specific phenomenon, considering the strong HIV-1 inhibition in co-infected cells.

  3. The Mathematical Biology of Human Infections

    Directory of Open Access Journals (Sweden)

    Martin A. Nowak

    1999-12-01

    Full Text Available Humans are constant victims of infectious diseases. Biomedical research during this century has led to important insights into the molecular details of immune defense. Yet, many questions relating to disease require a quantitative understanding of the complex systems that arise from the nonlinear interactions between populations of immune cells and infectious agents. Exploration of such questions has lead to a newly emerging field of mathematical biology describing the spread of infectious agents both within and between infected individuals. This essay will discuss simple and complex models of evolution, and the propagation of virus and prion infections. Such models provide new perspectives for our understanding of infectious disease and provide guidelines for interpreting experimental observation; they also define what needs to be measured to improve understanding.

  4. Dengue human infection models supporting drug development.

    Science.gov (United States)

    Whitehorn, James; Van, Vinh Chau Nguyen; Simmons, Cameron P

    2014-06-15

    Dengue is a arboviral infection that represents a major global health burden. There is an unmet need for effective dengue therapeutics to reduce symptoms, duration of illness and incidence of severe complications. Here, we consider the merits of a dengue human infection model (DHIM) for drug development. A DHIM could allow experimentally controlled studies of candidate therapeutics in preselected susceptible volunteers, potentially using smaller sample sizes than trials that recruited patients with dengue in an endemic country. In addition, the DHIM would assist the conduct of intensive pharmacokinetic and basic research investigations and aid in determining optimal drug dosage. Furthermore, a DHIM could help establish proof of concept that chemoprophylaxis against dengue is feasible. The key challenge in developing the DHIM for drug development is to ensure the model reliably replicates the typical clinical and laboratory features of naturally acquired, symptomatic dengue. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  5. Actinomyces and related organisms in human infections.

    Science.gov (United States)

    Könönen, Eija; Wade, William G

    2015-04-01

    Actinomyces israelii has long been recognized as a causative agent of actinomycosis. During the past 3 decades, a large number of novel Actinomyces species have been described. Their detection and identification in clinical microbiology laboratories and recognition as pathogens in clinical settings can be challenging. With the introduction of advanced molecular methods, knowledge about their clinical relevance is gradually increasing, and the spectrum of diseases associated with Actinomyces and Actinomyces-like organisms is widening accordingly; for example, Actinomyces meyeri, Actinomyces neuii, and Actinomyces turicensis as well as Actinotignum (formerly Actinobaculum) schaalii are emerging as important causes of specific infections at various body sites. In the present review, we have gathered this information to provide a comprehensive and microbiologically consistent overview of the significance of Actinomyces and some closely related taxa in human infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Production of high-titer RCAS retrovirus.

    Science.gov (United States)

    Yan, Run-Tao; Wang, Shu-Zhen

    2012-01-01

    RCAS (B/P) is a replication-competent avian retrovirus engineered by Hughes et al. (J Virol 61:3004-3012, 1987) and is referred to in this chapter as RCAS for simplicity. The RCAS retrovirus has been widely used as a vehicle for stable transduction of a gene into cells both in the developing chick embryo and tissue/cell culture. It can be used for both gain- and loss-function experiments. The ability of this virus to spread among proliferating cells makes it possible to achieve widespread gene transduction in the developing retina. The transduction efficiency of RCAS is highly depending on the titer of the viral stock, particularly for experiments involving solid tissues such as the developing retina. Here, we describe the procedure that we have used for 15 years to generate RCAS viral stocks with a titer of 1-5 × 10(8) pfu/ml.

  7. Endogenous retroviruses are associated with autoimmune diseases

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Bisgaard Jensen, Sara; Hansen, Bettina

    2016-01-01

    of transmission is called vertical. Viral variants of importance for development of disease must be more frequent among diseased persons than among healthy individuals. Multiple sclerosis, diabetes and rheumatoid arthritis are all associated with sets of endogenouos retroviruses but not the same sets. If a virus...... grows and this contributes to disease, one should be able to alleviate disease with antiretroviral drugs. We call for clinical trials to elucidate this issue....

  8. Activation of the innate immune response by endogenous retroviruses.

    Science.gov (United States)

    Hurst, Tara P; Magiorkinis, Gkikas

    2015-06-01

    The human genome comprises 8 % endogenous retroviruses (ERVs), the majority of which are defective due to deleterious mutations. Nonetheless, transcripts of ERVs are found in most tissues, and these transcripts could either be reverse transcribed to generate ssDNA or expressed to generate proteins. Thus, the expression of ERVs could produce nucleic acids or proteins with viral signatures, much like the pathogen-associated molecular patterns of exogenous viruses, which would enable them to be detected by the innate immune system. The activation of some pattern recognition receptors (PRRs) in response to ERVs has been described in mice and in the context of human autoimmune diseases. Here, we review the evidence for detection of ERVs by PRRs and the resultant activation of innate immune signalling. This is an emerging area of research within the field of innate antiviral immunity, showing how ERVs could initiate immune signalling pathways and might have implications for numerous inflammatory diseases. © 2015 The Authors.

  9. Chemical Induction of Endogenous Retrovirus Particles from the Vero Cell Line of African Green Monkeys▿

    Science.gov (United States)

    Ma, Hailun; Ma, Yunkun; Ma, Wenbin; Williams, Dhanya K.; Galvin, Teresa A.; Khan, Arifa S.

    2011-01-01

    Endogenous retroviral sequences are present in high copy numbers in the genomes of all species and may be expressed as RNAs; however, the majority are defective for virus production. Although virus has been isolated from various Old World monkey and New World monkey species, there has been no report of endogenous retroviruses produced from African green monkey (AGM) tissues or cell lines. We have recently developed a stepwise approach for evaluating the presence of latent viruses by chemical induction (Khan et al., Biologicals 37:196–201, 2009). Based upon this strategy, optimum conditions were determined for investigating the presence of inducible, endogenous retroviruses in the AGM-derived Vero cell line. Low-level reverse transcriptase activity was produced with 5-azacytidine (AzaC) and with 5′-iodo-2′-deoxyuridine (IUdR); none was detected with sodium butyrate. Nucleotide sequence analysis of PCR-amplified fragments from the gag, pol, and env regions of RNAs, prepared from ultracentrifuged pellets of filtered supernatants, indicated that endogenous retrovirus particles related to simian endogenous type D betaretrovirus (SERV) sequences and baboon endogenous virus type C gammaretrovirus (BaEV) sequences were induced by AzaC, whereas SERV sequences were also induced by IUdR. Additionally, sequence heterogeneity was seen in the RNAs of SERV- and BaEV-related particles. Infectivity analysis of drug-treated AGM Vero cells showed no virus replication in cell lines known to be susceptible to type D simian retroviruses (SRVs) and to BaEV. The results indicated that multiple, inducible endogenous retrovirus loci are present in the AGM genome that can encode noninfectious, viruslike particles. PMID:21543506

  10. tirant, a newly discovered active endogenous retrovirus in Drosophila simulans.

    Science.gov (United States)

    Akkouche, Abdou; Rebollo, Rita; Burlet, Nelly; Esnault, Caroline; Martinez, Sonia; Viginier, Barbara; Terzian, Christophe; Vieira, Cristina; Fablet, Marie

    2012-04-01

    Endogenous retroviruses have the ability to become permanently integrated into the genomes of their host, and they are generally transmitted vertically from parent to progeny. With the exception of gypsy, few endogenous retroviruses have been identified in insects. In this study, we describe the tirant endogenous retrovirus in a subset of Drosophila simulans natural populations. By focusing on the envelope gene, we show that the entire retroviral cycle (transcription, translation, and retrotransposition) can be completed for tirant within one population of this species.

  11. Early steps of retrovirus replicative cycle

    Directory of Open Access Journals (Sweden)

    Saïb Ali

    2004-05-01

    Full Text Available Abstract During the last two decades, the profusion of HIV research due to the urge to identify new therapeutic targets has led to a wealth of information on the retroviral replication cycle. However, while the late stages of the retrovirus life cycle, consisting of virus replication and egress, have been partly unraveled, the early steps remain largely enigmatic. These early steps consist of a long and perilous journey from the cell surface to the nucleus where the proviral DNA integrates into the host genome. Retroviral particles must bind specifically to their target cells, cross the plasma membrane, reverse-transcribe their RNA genome, while uncoating the cores, find their way to the nuclear membrane and penetrate into the nucleus to finally dock and integrate into the cellular genome. Along this journey, retroviruses hijack the cellular machinery, while at the same time counteracting cellular defenses. Elucidating these mechanisms and identifying which cellular factors are exploited by the retroviruses and which hinder their life cycle, will certainly lead to the discovery of new ways to inhibit viral replication and to improve retroviral vectors for gene transfer. Finally, as proven by many examples in the past, progresses in retrovirology will undoubtedly also provide some priceless insights into cell biology.

  12. Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV).

    Science.gov (United States)

    Denner, Joachim

    2016-12-20

    Transspecies transmission of retroviruses is a frequent event, and the human immunodeficiency virus-1 (HIV-1) is a well-known example. The gibbon ape leukaemia virus (GaLV) and koala retrovirus (KoRV), two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. Related retroviruses have been found in Southeast Asian mice although the sequence similarity was limited. Viruses with a higher sequence homology were isolated from Melomys burtoni, the Australian and Indonesian grassland melomys. However, only the habitats of the koalas and the grassland melomys in Australia are overlapping, indicating that the melomys virus may not be the precursor of the GaLV. Viruses closely related to GaLV/KoRV were also detected in bats. Therefore, given the fact that the habitats of the gibbons in Thailand and the koalas in Australia are far away, and that bats are able to fly over long distances, the hypothesis that retroviruses of bats are the origin of GaLV and KoRV deserves consideration. Analysis of previous transspecies transmissions of retroviruses may help to evaluate the potential of transmission of related retroviruses in the future, e.g., that of porcine endogenous retroviruses (PERVs) during xenotransplantation using pig cells, tissues or organs.

  13. Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV and the Koala Retrovirus (KoRV

    Directory of Open Access Journals (Sweden)

    Joachim Denner

    2016-12-01

    Full Text Available Transspecies transmission of retroviruses is a frequent event, and the human immunodeficiency virus-1 (HIV-1 is a well-known example. The gibbon ape leukaemia virus (GaLV and koala retrovirus (KoRV, two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. Related retroviruses have been found in Southeast Asian mice although the sequence similarity was limited. Viruses with a higher sequence homology were isolated from Melomys burtoni, the Australian and Indonesian grassland melomys. However, only the habitats of the koalas and the grassland melomys in Australia are overlapping, indicating that the melomys virus may not be the precursor of the GaLV. Viruses closely related to GaLV/KoRV were also detected in bats. Therefore, given the fact that the habitats of the gibbons in Thailand and the koalas in Australia are far away, and that bats are able to fly over long distances, the hypothesis that retroviruses of bats are the origin of GaLV and KoRV deserves consideration. Analysis of previous transspecies transmissions of retroviruses may help to evaluate the potential of transmission of related retroviruses in the future, e.g., that of porcine endogenous retroviruses (PERVs during xenotransplantation using pig cells, tissues or organs.

  14. Hare TRIM5α Restricts Divergent Retroviruses and Exhibits Significant Sequence Variation from Closely Related Lagomorpha TRIM5 Genes▿

    Science.gov (United States)

    Fletcher, Adam J.; Hué, Stéphane; Schaller, Torsten; Pillay, Deenan; Towers, Greg J.

    2010-01-01

    TRIM5α proteins recruit and restrict incoming cytoplasmic retroviruses. Primate TRIM5α sequence diversity underlies species-specific restriction and is likely caused by selective pressure from ancient pathogenic infections. Here we show that TRIM5α from the European brown hare restricts diverse retroviruses. Furthermore, it differs significantly in sequence from TRIM5α from the closely related rabbit, suggesting evolutionary changes in the last 12 million years since these species diverged. We propose that, like primates, lagomorphs have been subject to selective pressure from TRIM5-sensitive viruses, possibly related to the endogenous lentivirus RELIK found in both rabbits and hares. PMID:20861252

  15. Hare TRIM5α restricts divergent retroviruses and exhibits significant sequence variation from closely related lagomorpha TRIM5 genes.

    Science.gov (United States)

    Fletcher, Adam J; Hué, Stéphane; Schaller, Torsten; Pillay, Deenan; Towers, Greg J

    2010-12-01

    TRIM5α proteins recruit and restrict incoming cytoplasmic retroviruses. Primate TRIM5α sequence diversity underlies species-specific restriction and is likely caused by selective pressure from ancient pathogenic infections. Here we show that TRIM5α from the European brown hare restricts diverse retroviruses. Furthermore, it differs significantly in sequence from TRIM5α from the closely related rabbit, suggesting evolutionary changes in the last 12 million years since these species diverged. We propose that, like primates, lagomorphs have been subject to selective pressure from TRIM5-sensitive viruses, possibly related to the endogenous lentivirus RELIK found in both rabbits and hares.

  16. Microbiological diagnosis of human papilloma virus infection.

    Science.gov (United States)

    Mateos-Lindemann, Maria Luisa; Pérez-Castro, Sonia; Rodríguez-Iglesias, Manuel; Pérez-Gracia, Maria Teresa

    2017-11-01

    Infection with human papillomavirus (HPV) is the leading cause of sexually transmitted infection worldwide. This virus generally causes benign lesions, such as genital warts, but persistent infection may lead to cervical cancer, anal cancer, vaginal cancer, and oropharyngeal cancer, although less frequently. Cervical cancer is a severe disease with a high mortality in some countries. Screening with cytology has been very successful in the last few years, but nowadays there are numerous studies that confirm that cytology should be replaced with the detection of HPV as a first line test in population based screening. There are several commercially available FDA approved tests for screening of cervical cancer. A new strategy, based on individual detection of the high risk genotypes HPV16 and HPV18, present in 70% of cervical cancer biopsies, has been proposed by some experts, and is going to be implemented in most countries in the future. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  17. Human papilloma virus infection prior to coitarche.

    Science.gov (United States)

    Doerfler, Daniela; Bernhaus, Astrid; Kottmel, Andrea; Sam, Christine; Koelle, Dieter; Joura, Elmar A

    2009-05-01

    The aim of our study was to determine the prevalence and the natural course of anogenital human papilloma virus (HPV) infections in girls prior to coitarche attending an outpatient gynecological unit. Specimens were taken from the anogenital region of 114 unselected 4-15 year old girls who were referred consecutively for various gynecological problems. Four girls were excluded because of sexual abuse. Low-risk HPV-deoxyribonucleic acid (DNA) was detected in 4 girls (3.6%) and high-risk HPV DNA in 15 children (13.6%). Two girls testing positive for HPV DNA had clinical apparent warts. After 1 year, 2 children had persistent high-risk HPV DNA, and in 1 case we found a switch from high-risk to low-risk HPV DNA. Subclinical genital low- and high-risk HPV infections are common in girls without any history of sexual abuse or sexual activity. We found persistence of genital HPV infection in children, which could be a reservoir for HPV-associated diseases later in life.

  18. Human immunodeficiency virus infection and child sexual abuse

    African Journals Online (AJOL)

    Human immunodeficiency virus infection and child sexual abuse. Hendrik Simon Schaaf. Child sexual abuse (CSA) has not previously been regarded as important in the overall transmission of HIV infection to. childrenY However, with both CSA'·' and HIV infection on the increase, the risk of acquiring HIV infection through ...

  19. Discovery of a novel retrovirus sequence in an Australian native rodent (Melomys burtoni: a putative link between gibbon ape leukemia virus and koala retrovirus.

    Directory of Open Access Journals (Sweden)

    Greg Simmons

    Full Text Available Gibbon ape leukaemia virus (GALV and koala retrovirus (KoRV share a remarkably close sequence identity despite the fact that they occur in distantly related mammals on different continents. It has previously been suggested that infection of their respective hosts may have occurred as a result of a species jump from another, as yet unidentified vertebrate host. To investigate possible sources of these retroviruses in the Australian context, DNA samples were obtained from 42 vertebrate species and screened using PCR in order to detect proviral sequences closely related to KoRV and GALV. Four proviral partial sequences totalling 2880 bases which share a strong similarity with KoRV and GALV were detected in DNA from a native Australian rodent, the grassland melomys, Melomys burtoni. We have designated this novel gammaretrovirus Melomys burtoni retrovirus (MbRV. The concatenated nucleotide sequence of MbRV shares 93% identity with the corresponding sequence from GALV-SEATO and 83% identity with KoRV. The geographic ranges of the grassland melomys and of the koala partially overlap. Thus a species jump by MbRV from melomys to koalas is conceivable. However the genus Melomys does not occur in mainland South East Asia and so it appears most likely that another as yet unidentified host was the source of GALV.

  20. Discovery of a novel retrovirus sequence in an Australian native rodent (Melomys burtoni): a putative link between gibbon ape leukemia virus and koala retrovirus.

    Science.gov (United States)

    Simmons, Greg; Clarke, Daniel; McKee, Jeff; Young, Paul; Meers, Joanne

    2014-01-01

    Gibbon ape leukaemia virus (GALV) and koala retrovirus (KoRV) share a remarkably close sequence identity despite the fact that they occur in distantly related mammals on different continents. It has previously been suggested that infection of their respective hosts may have occurred as a result of a species jump from another, as yet unidentified vertebrate host. To investigate possible sources of these retroviruses in the Australian context, DNA samples were obtained from 42 vertebrate species and screened using PCR in order to detect proviral sequences closely related to KoRV and GALV. Four proviral partial sequences totalling 2880 bases which share a strong similarity with KoRV and GALV were detected in DNA from a native Australian rodent, the grassland melomys, Melomys burtoni. We have designated this novel gammaretrovirus Melomys burtoni retrovirus (MbRV). The concatenated nucleotide sequence of MbRV shares 93% identity with the corresponding sequence from GALV-SEATO and 83% identity with KoRV. The geographic ranges of the grassland melomys and of the koala partially overlap. Thus a species jump by MbRV from melomys to koalas is conceivable. However the genus Melomys does not occur in mainland South East Asia and so it appears most likely that another as yet unidentified host was the source of GALV.

  1. Phylogenetic Diversity of Koala Retrovirus within a Wild Koala Population.

    Science.gov (United States)

    Chappell, K J; Brealey, J C; Amarilla, A A; Watterson, D; Hulse, L; Palmieri, C; Johnston, S D; Holmes, E C; Meers, J; Young, P R

    2017-02-01

    Koala populations are in serious decline across many areas of mainland Australia, with infectious disease a contributing factor. Koala retrovirus (KoRV) is a gammaretrovirus present in most wild koala populations and captive colonies. Five subtypes of KoRV (A to E) have been identified based on amino acid sequence divergence in a hypervariable region of the receptor binding domain of the envelope protein. However, analysis of viral genetic diversity has been conducted primarily on KoRV in captive koalas housed in zoos in Japan, the United States, and Germany. Wild koalas within Australia have not been comparably assessed. Here we report a detailed analysis of KoRV genetic diversity in samples collected from 18 wild koalas from southeast Queensland. By employing deep sequencing we identified 108 novel KoRV envelope sequences and determined their phylogenetic diversity. Genetic diversity in KoRV was abundant and fell into three major groups; two comprised the previously identified subtypes A and B, while the third contained the remaining hypervariable region subtypes (C, D, and E) as well as four hypervariable region subtypes that we newly define here (F, G, H, and I). In addition to the ubiquitous presence of KoRV-A, which may represent an exclusively endogenous variant, subtypes B, D, and F were found to be at high prevalence, while subtypes G, H, and I were present in a smaller number of animals. Koala retrovirus (KoRV) is thought to be a significant contributor to koala disease and population decline across mainland Australia. This study is the first to determine KoRV subtype prevalence among a wild koala population, and it significantly expands the total number of KoRV sequences available, providing a more precise picture of genetic diversity. This understanding of KoRV subtype prevalence and genetic diversity will be important for conservation efforts attempting to limit the spread of KoRV. Furthermore, KoRV is one of the only retroviruses shown to exist in

  2. Humanized mouse model to study bacterial infections targeting the microvasculature.

    Science.gov (United States)

    Melican, Keira; Aubey, Flore; Duménil, Guillaume

    2014-04-01

    Neisseria meningitidis causes a severe, frequently fatal sepsis when it enters the human blood stream. Infection leads to extensive damage of the blood vessels resulting in vascular leak, the development of purpuric rashes and eventual tissue necrosis. Studying the pathogenesis of this infection was previously limited by the human specificity of the bacteria, which makes in vivo models difficult. In this protocol, we describe a humanized model for this infection in which human skin, containing dermal microvessels, is grafted onto immunocompromised mice. These vessels anastomose with the mouse circulation while maintaining their human characteristics. Once introduced into this model, N. meningitidis adhere exclusively to the human vessels, resulting in extensive vascular damage, inflammation and in some cases the development of purpuric rash. This protocol describes the grafting, infection and evaluation steps of this model in the context of N. meningitidis infection. The technique may be applied to numerous human specific pathogens that infect the blood stream.

  3. Sudden cardiac death in patients with human immunodeficiency virus infection

    National Research Council Canada - National Science Library

    Tseng, Zian H; Secemsky, Eric A; Dowdy, David; Vittinghoff, Eric; Moyers, Brian; Wong, Joseph K; Havlir, Diane V; Hsue, Priscilla Y

    2012-01-01

    ...) in patients with human immunodeficiency virus (HIV) infection. As the HIV-infected population ages, cardiovascular disease prevalence and mortality are increasing, but the incidence and features of SCD have not yet been described...

  4. Human immunodeficiency virus infection and female lower genital tract malignancy.

    Science.gov (United States)

    Kuhn, L; Sun, X W; Wright, T C

    1999-02-01

    The risk of lower genital tract neoplasia is increased in women infected with HIV. This has been best demonstrated in cervical squamous intraepithelial lesions, but has also been observed in vulvar and perianal intraepithelial lesions in some studies. Alterations in the prevalence and natural history of human papillomavirus infections of the lower genital tract appear to account for much of the increase. HIV-infected women are approximately four times more likely to be infected with human papillomavirus (including infection with high oncogenic risk human papillomavirus types) than are HIV-uninfected women, and these infections are more likely to be persistent. Human papilomavirus-associated lesions may be more difficult to treat in HIV-infected women. These data highlight the need to develop effective cervical cancer prevention programs for HIV-infected women.

  5. Adaptation of a retrovirus as a eucaryotic vector transmitting the herpes simplex virus thymidine kinase gene.

    Science.gov (United States)

    Tabin, C J; Hoffmann, J W; Goff, S P; Weinberg, R A

    1982-01-01

    We investigated the feasibility of using retroviruses as vectors for transferring DNA sequences into animal cells. The thymidine kinase (tk) gene of herpes simplex virus was chosen as a convenient model. The internal BamHI fragments of a DNA clone of Moloney leukemia virus (MLV) were replaced with a purified BamHI DNA segment containing the tk gene. Chimeric genomes were created carrying the tk insert in both orientations relative to the MLV sequence. Each was transfected into TK- cells along with MLV helper virus, and TK+ colonies were obtained by selection in the presence of hypoxanthine, aminopterin, and thymidine (HAT). Virus collected from TK+-transformed, MLV producer cells passed the TK+ phenotype to TK- cells. Nonproducer cells were isolated, and TK+ transducing virus was subsequently rescued from them. The chimeric virus showed single-hit kinetics in infections. Virion and cellular RNA and cellular DNA from infected cells were all shown to contain sequences which hybridized to both MLV- and tk-specific probes. The sizes of these sequences were consistent with those predicted for the chimeric virus. In all respects studied, the chimeric MLV-tk virus behaved like known replication-defective retroviruses. These experiments suggest great general applicability of retroviruses as eucaryotic vectors. Images PMID:6180306

  6. One hundred twenty years of koala retrovirus evolution determined from museum skins.

    Science.gov (United States)

    Ávila-Arcos, María C; Ho, Simon Y W; Ishida, Yasuko; Nikolaidis, Nikolas; Tsangaras, Kyriakos; Hönig, Karin; Medina, Rebeca; Rasmussen, Morten; Fordyce, Sarah L; Calvignac-Spencer, Sébastien; Willerslev, Eske; Gilbert, M Thomas P; Helgen, Kristofer M; Roca, Alfred L; Greenwood, Alex D

    2013-02-01

    Although endogenous retroviruses are common across vertebrate genomes, the koala retrovirus (KoRV) is the only retrovirus known to be currently invading the germ line of its host. KoRV is believed to have first infected koalas in northern Australia less than two centuries ago. We examined KoRV in 28 koala museum skins collected in the late 19th and 20th centuries and deep sequenced the complete proviral envelope region from five northern Australian specimens. Strikingly, KoRV env sequences were conserved among koalas collected over the span of a century, and two functional motifs that affect viral infectivity were fixed across the museum koala specimens. We detected only 20 env polymorphisms among the koalas, likely representing derived mutations subject to purifying selection. Among northern Australian koalas, KoRV was already ubiquitous by the late 19th century, suggesting that KoRV evolved and spread among koala populations more slowly than previously believed. Given that museum and modern koalas share nearly identical KoRV sequences, it is likely that koala populations, for more than a century, have experienced increased susceptibility to diseases caused by viral pathogenesis.

  7. Differential sensitivity of porcine endogenous retrovirus to APOBEC3-mediated inhibition.

    Science.gov (United States)

    Park, Sung-Han; Kim, Jin Ha; Jung, Yong-Tae

    2015-08-01

    Pigs are considered to be suitable xenotransplantation organ donors. However, the risk of pathogen transmission from pigs to humans is a major concern in the transplantation of porcine tissues. The porcine endogenous retroviruses (PERVs) PERV-A, PERV-A/C, and PERV-B can infect human cells, but PERV-C is an ecotropic virus infecting only pig cells. Thus, several strategies have been proposed to reduce PERV transmission in xenograft recipients. Human APOBEC3G (huA3G) is a single-strand DNA cytosine deaminase, which inactivates the coding capacity of the virus by deamination of cDNA cytosines to uracils. This reaction occurs within the (-) DNA strand during reverse transcription, resulting in a G-to-A mutation in the (+) strand. While recent data have shown that PERV-B is severely inhibited by huA3G and porcine A3Z2-Z3 (poA3F) in a pseudotype assay, little is known about PERV-C. Here, we compare the antiretroviral activities of huA3G, huA3F and poA3Z2-Z3 against PERV-C. Our data show that APOBEC3 was packaged into PERV-C particles and inhibited PERV-C replication in a dose-dependent manner. PERV-C infectivity was strongly inhibited by poA3Z2-Z3, but it did not markedly reduce PERV-B infectivity. This suggests that PERV-C Gag interacts efficiently with poA3Z2-Z3. In addition, we constructed stably huA3G- and poA3Z2-Z3-expressing 293-PERV-PK-CIRCE cells (human 293 cells infected with PK15-derived PERVs) to examine whether PERV is resistant to poA3Z2-Z3 in a virus-spreading assay. The stably expressed huA3G and poA3Z2-Z3 were more packaging-competent than transiently expressed APOBEC3 proteins. These results suggest that poA3Z2-Z3 can inhibit PERV replication in a pseudotype assay as well as in a virus-spreading assay.

  8. Plant retroviruses: structure, evolution and future applications | Zaki ...

    African Journals Online (AJOL)

    Until recently, retroviruses were thought to be restricted to vertebrates. Plant sequencing projects revealed that plant genomes contain retroviral-like sequences. This review aims to address the structure and evolution of plant retroviruses. In addition, it proposes future applications for these important key components of plant ...

  9. Human Immunodeficiency Virus Infection in Pregnancy

    Directory of Open Access Journals (Sweden)

    Yasemin Arikan

    1998-01-01

    Full Text Available The incidence and prevalence of human immunodeficiency virus (HIV infection in women of child-bearing age continue to increase both internationally and in Canada. The care of HIV-infected pregnant women is complex, and multiple issues must be addressed, including the current and future health of the woman, minimization of the risk of maternal-infant HIV transmission, and maintenance of the well-being of the fetus and neonate. Vertical transmission of HIV can occur in utero, intrapartum and postpartum, but current evidence suggests that the majority of transmission occurs toward end of term, or during labour and delivery. Several maternal and obstetrical factors influence transmission rates, which can be reduced by optimal medical and obstetrical care. Zidovudine therapy has been demonstrated to reduce maternal-infant transmission significantly, but several issues, including the short and long term safety of antiretrovirals and the optimal use of combination antiretroviral therapy in pregnancy, remain to be defined. It is essential that health care workers providing care to these women fully understand the natural history of HIV disease in pregnancy, the factors that affect vertical transmission and the management issues during pregnancy. Close collaboration among a multidisciplinary team of knowledgeable health professionals and, most importantly, the woman herself can improve both maternal and infant outcomes.

  10. New treatments for human papillomavirus infection.

    Science.gov (United States)

    Muñoz-Santos, C; Pigem, R; Alsina, M

    2013-12-01

    Human papillomavirus infection is very common. In this article, we review the latest developments in the treatment of lesions caused by this virus, with a particular focus on anogenital warts. Sinecatechins and new imiquimod formulations are among the most significant new developments. Others include photodynamic therapy and intralesional immunotherapy, but there is insufficient evidence to recommend their routine use. Finally, while therapeutic vaccines and inhibitory molecules appear to hold great promise, they are still in the early phases of investigation. More studies are needed, and these should have similar designs, larger samples, and sufficiently long follow-up periods to enable the direct comparison of the short-term and long-term effectiveness of different treatment options. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  11. Modeling human influenza infection in the laboratory

    Directory of Open Access Journals (Sweden)

    Radigan KA

    2015-08-01

    Full Text Available Kathryn A Radigan,1 Alexander V Misharin,2 Monica Chi,1 GR Scott Budinger11Division of Pulmonary and Critical Care Medicine, 2Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models – mice and ferrets – most frequently used by researchers as models of human influenza infection.Keywords: mice, ferret, influenza, animal model, biosafety

  12. Anti-viral activity of red microalgal polysaccharides against retroviruses

    Directory of Open Access Journals (Sweden)

    Huleihel Mahmoud M

    2002-07-01

    Full Text Available Abstract Red microalgal polysaccharides significantly inhibited the production of retroviruses (murine leukemia virus- MuLV and cell transformation by murine sarcoma virus(MuSV-124 in cell culture. The most effective inhibitory effect of these polysaccharides against both cell transformation and virus production was obtained when the polysaccharide was added 2 h before or at the time of infection. Although, addition of the polysaccharide post-infection significantly reduced the number of transformed cells, but its effect was less marked than that obtained when the polysaccharide was added before or at the time of infection.The finding that the inhibition of cell transformation by MuSV-124 was reversible after removal of the polysaccharide suggested that microalgal polysaccharides inhibited a late step after provirus integration into the host genome. In conclusion, our findings could support the possibility that the polysaccharide may affect early steps in the virus replication cycle, such as virus absorption into the host cells, in addition to its effect on a late step after provirus integration.

  13. Anal Human Papillomavirus Infection among HIV-Infected Men in Korea.

    Science.gov (United States)

    Lee, Chang Hun; Lee, Sun Hee; Lee, Shinwon; Cho, Heerim; Kim, Kye-Hyung; Lee, Jung Eun; Jung, Eun Ju; Lee, Su Jin; Kim, Eun Jung; Kim, Ki Hyung; Moon, Eunsoo; Cho, Hong Je

    2016-01-01

    Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour. A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM) and 68 from men who have sex with women (MSW). Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection. Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age.

  14. Simian Foamy Virus in Non-Human Primates and Cross-Species Transmission to Humans in Gabon: An Emerging Zoonotic Disease in Central Africa?

    Directory of Open Access Journals (Sweden)

    Augustin Mouinga-Ondémé

    2013-06-01

    Full Text Available It is now known that all human retroviruses have a non-human primate counterpart. It has been reported that the presence of these retroviruses in humans is the result of interspecies transmission. Several authors have described the passage of a simian retrovirus, simian foamy virus (SFV, from primates to humans. To better understand this retroviral “zoonosis” in natural settings, we evaluated the presence of SFV in both captive and wild non-human primates and in humans at high risk, such as hunters and people bitten by a non-human primate, in Gabon, central Africa. A high prevalence of SFV was found in blood samples from non-human primates and in bush meat collected across the country. Mandrills were found to be highly infected with two distinct strains of SFV, depending on their geographical location. Furthermore, samples collected from hunters and non-human primate laboratory workers showed clear, extensive cross-species transmission of SFV. People who had been bitten by mandrills, gorillas and chimpanzees had persistent SFV infection with low genetic drift. Thus, SFV is presumed to be transmitted from non-human primates mainly through severe bites, involving contact between infected saliva and blood. In this review, we summarize and discuss our five-year observations on the prevalence and dissemination of SFV in humans and non-human primates in Gabon.

  15. Simian foamy virus in non-human primates and cross-species transmission to humans in Gabon: an emerging zoonotic disease in central Africa?

    Science.gov (United States)

    Mouinga-Ondémé, Augustin; Kazanji, Mirdad

    2013-06-19

    It is now known that all human retroviruses have a non-human primate counterpart. It has been reported that the presence of these retroviruses in humans is the result of interspecies transmission. Several authors have described the passage of a simian retrovirus, simian foamy virus (SFV), from primates to humans. To better understand this retroviral "zoonosis" in natural settings, we evaluated the presence of SFV in both captive and wild non-human primates and in humans at high risk, such as hunters and people bitten by a non-human primate, in Gabon, central Africa. A high prevalence of SFV was found in blood samples from non-human primates and in bush meat collected across the country. Mandrills were found to be highly infected with two distinct strains of SFV, depending on their geographical location. Furthermore, samples collected from hunters and non-human primate laboratory workers showed clear, extensive cross-species transmission of SFV. People who had been bitten by mandrills, gorillas and chimpanzees had persistent SFV infection with low genetic drift. Thus, SFV is presumed to be transmitted from non-human primates mainly through severe bites, involving contact between infected saliva and blood. In this review, we summarize and discuss our five-year observations on the prevalence and dissemination of SFV in humans and non-human primates in Gabon.

  16. Anal Human Papillomavirus Infection among HIV-Infected Men in Korea

    OpenAIRE

    Lee, Chang Hun; Lee, Sun Hee; Lee, Shinwon; Cho, Heerim; Kim, Kye-Hyung; Lee, Jung Eun; Jung, Eun ju; Lee, Su Jin; Kim, Eun Jung; Kim, Ki Hyung; Moon, Eunsoo; Cho, Hong Je

    2016-01-01

    Background Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. Methods A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytol...

  17. Anal Human Papillomavirus Infection among HIV-Infected Men in Korea

    Science.gov (United States)

    Lee, Chang Hun; Lee, Sun Hee; Lee, Shinwon; Cho, Heerim; Kim, Kye-Hyung; Lee, Jung Eun; Jung, Eun ju; Lee, Su jin; Kim, Eun Jung; Kim, Ki Hyung; Moon, Eunsoo; Cho, Hong Je

    2016-01-01

    Background Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. Methods A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour. Results A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM) and 68 from men who have sex with women (MSW). Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection. Conclusion Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age. PMID:27548632

  18. An avian, oncogenic retrovirus replicates in vivo in more than 50% of CD4+ and CD8+ T lymphocytes from an endangered grouse

    Science.gov (United States)

    Reoccurring infection of reticuloendotheliosis virus (REV), an avian oncogenic retrovirus, has been a major obstacle in attempts to breed and release an endangered grouse, the Attwater's prairie chicken (Tympanicus cupido attwateri). REV infection of these birds in breeding facilities was found to r...

  19. Existence of proviral porcine endogenous retrovirus in fresh and decellularised porcine tissues

    OpenAIRE

    Prabha S; Verghese S

    2008-01-01

    Purpose: Swine are expected to be utilized as xenograft donors for both whole organ and cellular transplantation. A major concern in using porcine organs for transplantation is the potential of transmission of porcine endogenous retrovirus (PERV). Tissue-engineered or decellularised heart valves have already been implanted in humans and have been marketed by certain companies after Food and Drug Administration (FDA) approval. The aim of this study was to examine the existence of porcine endo...

  20. Improving Psychological Response on Indonesian's Migrant Worker (TKI) Infected by HIV Through Family and Peer Group Support

    OpenAIRE

    Sukartini, Tintin Sukartini; Nursalam, Nursalam Nursalam; M.Has, Eka Mishbahatul; Asmoro, Candra Panji; Misutarno, Misutarno Misutarno

    2016-01-01

    Introduction: Human Immunodeficiency Virus (HIV) is a retrovirus that infects cells of the immune system, destroying or damaging the function of cells of the immune system. This makes the immune system becomes weaker, and people become more liable to infection. A lot of new detected HIV transmission source comes from former workers who work abroad. The challenge is how to improve the psychological response of people living with HIV (PLWHA) to be able to socialize confident and not worry about...

  1. Pathogenesis of Hendra and Nipah virus infection in humans.

    Science.gov (United States)

    Escaffre, Olivier; Borisevich, Viktoriya; Rockx, Barry

    2013-04-17

    Hendra virus (HeV) and Nipah virus (NiV) are emerging zoonotic viruses that cause severe and often lethal respiratory illness and encephalitis in humans. Henipaviruses can infect a wide range of species and human-to-human transmission has been observed for NiV. While the exact route of transmission in humans is not known, experimental infection in different animal species suggests that infection can be efficiently initiated after respiratory challenge. The limited data on histopathological changes in fatal human cases of HeV and NiV suggest that endothelial cells are an important target during the terminal stage of infection; however, it is unknown where these viruses initially establish infection and how the virus disseminates from the respiratory tract to the central nervous system and other organs. Here we review the current concepts in henipavirus pathogenesis in humans.

  2. Hepatitis C Virus and Human Immunodeficiency Virus Co-Infection ...

    African Journals Online (AJOL)

    Background: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are major health problems worldwide. HCV/HIV co-infection has been shown to increase the frequency of liver disease and also maternal-fetal transmission of HCV. Little data exist on the prevalence of co-infection of these viruses in ...

  3. Human papillomavirus infection and disease in men: Impact of HIV ...

    African Journals Online (AJOL)

    There is growing evidence of a significant burden of human papillomavirus (HPV) infection and associated disease in men. High rates of HPV infection have been observed in men from sub-Saharan Africa where HIV prevalence is high. HIV infection increases HPV prevalence, incidence and persistence and is strongly ...

  4. Can Helicobacter pylori infection influence human reproduction?

    OpenAIRE

    Moretti, Elena; Figura, Natale; Collodel, Giulia; Ponzetto, Antonio

    2014-01-01

    Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermato...

  5. Activation of endogenous retrovirus reverse transcriptase in multiple sclerosis patient lymphocytes by inactivated HSV-1, HHV-6 and VZV

    DEFF Research Database (Denmark)

    Brudek, Tomasz; Lühdorf, Pernille; Christensen, Tove

    2007-01-01

    Human endogenous retroviruses (HERVs) and herpesviruses have been associated with the development of multiple sclerosis (MS). These virus groups interact with each other and have been shown to induce synergistic immune responses. Here, we focus on the possible role of herpesviruses as contributing...

  6. p53 as a retrovirus-induced oxidative stress modulator.

    Science.gov (United States)

    Kim, Soo Jin; Wong, Paul K Y

    2015-01-01

    Infection of astrocytes by the neuropathogenic mutant of Moloney murine leukemia virus, ts1, exhibits increased levels of reactive oxygen species (ROS) and signs of oxidative stress compared with uninfected astrocytes. Previously, we have demonstrated that ts1 infection caused two separate events of ROS upregulation. The first upregulation occurs during early viral establishment in host cells and the second during the virus-mediated apoptotic process. In this study, we show that virus-mediated ROS upregulation activates the protein kinase, ataxia telangiectasia mutated, which in turn phosphorylates serine 15 on p53. This activation of p53 however, is unlikely associated with ts1-induced cell death. Rather p53 appears to be involved in suppressing intracellular ROS levels in astrocytes under oxidative stress. The activated p53 appears to delay retroviral gene expression by suppressing NADPH oxidase, a superoxide-producing enzyme. These results suggest that p53 plays a role as a retrovirus-mediated oxidative stress modulator. © 2015 The Authors.

  7. Changes in microbiota during experimental human Rhinovirus infection

    NARCIS (Netherlands)

    Hofstra, J. J.; Matamoros, S.; van de Pol, M. A.; de Wever, B.; Tanck, M. W.; Wendt-Knol, H.; Deijs, M.; van der Hoek, L.; Wolthers, K. C.; Molenkamp, R.; Visser, C. E.; Sterk, P. J.; Lutter, R.; de Jong, M. D.

    2015-01-01

    Human Rhinovirus (HRV) is responsible for the majority of common colds and is frequently accompanied by secondary bacterial infections through poorly understood mechanisms. We investigated the effects of experimental human HRV serotype 16 infection on the upper respiratory tract microbiota. Six

  8. Arterial Disease in Patients With Human Immunodeficiency Virus Infection

    OpenAIRE

    Stein, James H.; Currier, Judith S.; HSUE, Priscilla Y

    2014-01-01

    With advances in antiretroviral therapy, individuals with human immunodeficiency virus (HIV) infection are living longer and increasingly die of non-HIV related diseases such as cardiovascular disease (CVD). Several observational studies suggest that HIV-infected patients on ART are at increased CVD risk; however, the precise mechanisms underlying the association between HIV infection and CVD risk are uncertain. Atherosclerosis and arterial disease in HIV-infected individuals is a multifactor...

  9. Human Papillomavirus Infection, Infertility, and Assisted Reproductive Outcomes

    OpenAIRE

    Nigel Pereira; Kucharczyk, Katherine M.; Estes, Jaclyn L.; Rachel S. Gerber; Jovana P. Lekovich; Elias, Rony T.; Spandorfer, Steven D.

    2015-01-01

    The human papillomavirus (HPV) is a sexually transmitted infection common among men and women across all geographic and socioeconomic subgroups worldwide. Recent evidence suggests that HPV infection may affect fertility and alter the efficacy of assisted reproductive technologies. In men, HPV infection can affect sperm parameters, specifically motility. HPV-infected sperm can transmit viral DNA to oocytes, which may be expressed in the developing blastocyst. HPV can increase trophoblastic apo...

  10. Barefoot Plantar Pressure Indicates Progressive Neurological Damage in Patients with Human T-Cell Lymphotropic Virus Type 1 Infection.

    Directory of Open Access Journals (Sweden)

    Beatriz Helena B Vasconcelos

    Full Text Available The human T-Cell Lymphotropic Virus Type 1 (HTLV-1 is a retrovirus associated with neurological alterations; individuals with HTLV-1 infection may develop HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP. Frequent neurological complaints include foot numbness and leg weakness. In this study, we compared the distribution of the body weight on different areas of the foot in HTLV-1 patients with HAM/TSP, asymptomatic HTLV-1 patients, and healthy individuals.We studied 36 HTLV-1 infected patients, who were divided in two groups of 18 patients each based on whether or not they had been diagnosed with HAM/TSP, and 17 control subjects. The evaluation included an interview on the patient's clinical history and examinations of the patient's reflexes, foot skin tactile sensitivity, and risk of falling. The pressure distribution on different areas of the foot was measured with baropodometry, using a pressure platform, while the patients had their eyes open or closed.The prevalence of neurological disturbances-altered reflexes and skin tactile sensitivity and increased risk of falling-was higher in HTLV-1 HAM/TSP patients than in HTLV-1 asymptomatic patients. The medium and maximum pressure values were higher in the forefoot than in the midfoot and hindfoot in both HTLV-1 groups. In addition, the pressure on the hindfoot was lower in HAM/TSP patients compared to control subjects.The neurological disturbances associated with HTLV-1 infection gradually worsened from HTLV-1 asymptomatic patients to HAM/TSP patients. Baropodometry is a valuable tool to establish the extent of neurological damage in patients suffering from HTLV-1 infection.

  11. Host-pathogen interactome mapping for HTLV-1 and -2 retroviruses

    Directory of Open Access Journals (Sweden)

    Simonis Nicolas

    2012-03-01

    Full Text Available Abstract Background Human T-cell leukemia virus type 1 (HTLV-1 and type 2 both target T lymphocytes, yet induce radically different phenotypic outcomes. HTLV-1 is a causative agent of Adult T-cell leukemia (ATL, whereas HTLV-2, highly similar to HTLV-1, causes no known overt disease. HTLV gene products are engaged in a dynamic struggle of activating and antagonistic interactions with host cells. Investigations focused on one or a few genes have identified several human factors interacting with HTLV viral proteins. Most of the available interaction data concern the highly investigated HTLV-1 Tax protein. Identifying shared and distinct host-pathogen protein interaction profiles for these two viruses would enlighten how they exploit distinctive or common strategies to subvert cellular pathways toward disease progression. Results We employ a scalable methodology for the systematic mapping and comparison of pathogen-host protein interactions that includes stringent yeast two-hybrid screening and systematic retest, as well as two independent validations through an additional protein interaction detection method and a functional transactivation assay. The final data set contained 166 interactions between 10 viral proteins and 122 human proteins. Among the 166 interactions identified, 87 and 79 involved HTLV-1 and HTLV-2 -encoded proteins, respectively. Targets for HTLV-1 and HTLV-2 proteins implicate a diverse set of cellular processes including the ubiquitin-proteasome system, the apoptosis, different cancer pathways and the Notch signaling pathway. Conclusions This study constitutes a first pass, with homogeneous data, at comparative analysis of host targets for HTLV-1 and -2 retroviruses, complements currently existing data for formulation of systems biology models of retroviral induced diseases and presents new insights on biological pathways involved in retroviral infection.

  12. Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection

    NARCIS (Netherlands)

    van Woensel, J. B. M.; Bos, A. P.; Lutter, R.; Rossen, J. W. A.; Schuurman, R.

    2006-01-01

    It has been suggested that co-infection of human metapneumovirus (hMPV) in severe respiratory syncytial (RSV) virus bronchiolitis is very common. To evaluate the epidemiology of hMPV co-infection in children with severe lower respiratory tract infection caused by RSV virus. This was an observational

  13. Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection

    NARCIS (Netherlands)

    van Woensel, J B M; Bos, A P; Lutter, R; Rossen, J W A; Schuurman, R

    It has been suggested that co-infection of human metapneumovirus (hMPV) in severe respiratory syncytial (RSV) virus bronchiolitis is very common. To evaluate the epidemiology of hMPV co-infection in children with severe lower respiratory tract infection caused by RSV virus. This was an observational

  14. [Cerebral infarction in human immunodeficiency virus infection].

    Science.gov (United States)

    Blanche, P; Toulon, P; de La Blanchardière, A; Sicard, D

    1995-06-03

    Patients infected with the human immunodeficiency virus (HIV) appear to have a high risk of ischaemic cerebral events. We observed two cases of cerebral infarction in patients with acquired immune deficiency syndrome (AIDS). In the first case, a 38-year-old homosexual with no cardiovascular risk other than smoking presented with rapidly progressive hemiparesia. Brain CT-scan visualized two infarcts in the territory of the right sylvian artery and the arteriography an occlusion of the internal carotid artery. In the second, a 37-year-old homosexual, hospitalization was required for a left-sided pure sensitive epilepsy seizure. There was no cardiovascular risk other than smoking. Magnetic resonance imaging showed parietal ischaemia and thrombus in the left atrium without atrial hypertrophy was seen at transoesophageal echocardiography. In both cases, there was no evidence of endocarditis, dissection of the neck vessels or disseminated intravascular coagulation nor of associated viral or bacterial infectious complication of AIDS. Angiographic findings eliminated cerebral vascularitis. Among the perturbed haemostasis factors previously reported in HIV+ patients, we observed free proteins S deficiency (68 and 43%) and heparin cofactor II deficiency (54 and 40%). Serum albumin was 33 and 32 g/l respectively. Outcome was favourable in both cases with anticoagulant therapy. These coagulation anomalies would not appear sufficient to explain cerebral infarction. Other mechanisms including immune complexed deposition, direct HIV toxicity for endothelial cells or the effect of cytokines on smooth muscles fibres and fibroblasts are probably more important causal factors.

  15. [The effect of retrovirus-mediated hTRT transfection into cultured oral keratinocytes].

    Science.gov (United States)

    Huang, Ji-yan; Liu, Wei; Zhou, Zeng-tong; Zhou, Hai-wen

    2014-06-01

    Human telomerase reverse transcriptase (hTRT) was transfected into cultured oral keratinocytes (OKC) mediated by pBABE-tert recombined retrovirus to investigate the effect on OKC lifespan. pBABE-tert recombined retrovirus loaded with hTRT gene was amplified by transfected PT67 cells, and then transfected into cultured OKC in vitro. The positive clones of OKC were separated by puromycin and subcultured. Telomerase activity was analyzed by telomerase PCR-ELISA and PCR-PAGE. The hTRT positive clones of OKC showed telomerase expression, with extending lifespan to 8-9 passages. The hTRT transfected OKC can prolong doubly lifespan but not be immortalized, which indicates that cellular immortality mechanism is complicated and multi-controled. Telomerase activity is the key for cell immortalization but not the only impact factor.

  16. Reciprocal relationship of T regulatory cells and monocytic myeloid-derived suppressor cells in LP-BM5 murine retrovirus-induced immunodeficiency.

    Science.gov (United States)

    O'Connor, Megan A; Vella, Jennifer L; Green, William R

    2016-02-01

    Immunomodulatory cellular subsets, including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs), contribute to the immunosuppressive tumour microenvironment and are targets of immunotherapy, but their role in retroviral-associated immunosuppression is less well understood. Due to known crosstalk between Tregs and MDSCs in the tumour microenvironment, and also their hypothesized involvement during human immunodeficiency virus/simian immunodeficiency virus infection, studying the interplay between these immune cells during LP-BM5 retrovirus-induced murine AIDS is of interest. IL-10-producing FoxP3+ Tregs expanded after LP-BM5 infection. Following in vivo adoptive transfer of natural Treg (nTreg)-depleted CD4+T-cells, and subsequent LP-BM5 retroviral infection, enriched monocytic MDSCs (M-MDSCs) from these nTreg-depleted mice displayed altered phenotypic subsets. In addition, M-MDSCs from LP-BM5-infected nTreg-depleted mice exhibited increased suppression of T-cell, but not B-cell, responses, compared with M-MDSCs derived from non-depleted LP-BM5-infected controls. Additionally, LP-BM5-induced M-MDSCs modulated the production of IL-10 by FoxP3+ Tregs in vitro. These collective data highlight in vitro and for the first time, to the best of our knowledge, in vivo reciprocal modulation between retroviral-induced M-MDSCs and Tregs, and may provide insight into the immunotherapeutic targeting of such regulatory cells during retroviral infection.

  17. Tetraspanins displayed in retrovirus-derived virus-like particles and their immunogenicity.

    Science.gov (United States)

    Soares, H R; Castro, R; Tomás, H A; Rodrigues, A F; Gomes-Alves, P; Bellier, B; Klatzmann, D; Carrondo, M J T; Alves, P M; Coroadinha, A S

    2016-03-18

    Virus-like particles (VLPs) are a particular subset of subunit vaccines which are currently explored as safer alternatives to live attenuated or inactivated vaccines. VLPs derived from retrovirus (retroVLPs) are commonly used as scaffolds for vaccine candidates due to their ability to incorporate heterologous envelope proteins. Pseudotyping retroVLPs is however not a selective process therefore, host cellular proteins such as tetraspanins are also included in the membrane. The contribution of these host-proteins to retrovirus immunogenicity remains unclear. In this work, human cells silenced and not silenced for tetraspanin CD81 were used to produce CD81(-) or CD81(+) retroVLPs. We first analyzed mice immune response against human CD81. Despite effective silencing of CD81 in retroVLP producing cells, both humoral and cellular immune responses showed persistent anti-CD81 immunogenicity, suggesting cross reactivity to related antigens. We thus compared the incorporation of related tetraspanins in retroVLPs and showed that decreased CD81 incorporation in CD81(-) retro-VLPs is compensated by an increased incorporation of CD9 and CD63 tetraspanins. These results highlight the dynamic nature of host-derived proteins incorporation in retroVLPs membrane, which should be considered when retrovirus-based biopharmaceuticals are produced in xenogeneic cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Prevalence and prognostic significance of infection with TT virus in patients infected with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Christensen, JK; Eugen-Olsen, Jesper; Sørensen, M

    2000-01-01

    No clear association between human disease and TT virus (TTV) has been documented. A possible pathogenic role of TTV was investigated in patients infected with human immunodeficiency virus (HIV). TTV serum concentrations were estimated in 185 HIV-infected patients by dilution polymerase chain rea...... TTV viremia (Psuspected to be an opportunistic pathogen with an independent influence on HIV progression....

  19. Human Infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013

    NARCIS (Netherlands)

    Memish, Ziad A.; Cotten, Matthew; Meyer, Benjamin; Watson, Simon J.; Alsahafi, Abdullah J.; Al Rabeeah, Abdullah A.; Corman, Victor Max; Sieberg, Andrea; Makhdoom, Hatem Q.; Assiri, Abdullah; Al Masri, Malaki; Aldabbagh, Souhaib; Bosch, Berend Jan|info:eu-repo/dai/nl/273306049; Beer, Martin; Müller, Marcel A.; Kellam, Paul; Drosten, Christian

    2014-01-01

    We investigated a case of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) after exposure to infected camels. Analysis of the whole human-derived virus and 15% of the camel-derived virus sequence yielded nucleotide polymorphism signatures suggestive of cross-species

  20. Factors Associated with Acquisition of Human Infective and Animal Infective Trypanosome Infections in Domestic Livestock in Western Kenya

    Science.gov (United States)

    von Wissmann, Beatrix; Machila, Noreen; Picozzi, Kim; Fèvre, Eric M.; deC. Bronsvoort, Barend M.; Handel, Ian G.; Welburn, Susan C.

    2011-01-01

    Background Trypanosomiasis is regarded as a constraint on livestock production in Western Kenya where the responsibility for tsetse and trypanosomiasis control has increasingly shifted from the state to the individual livestock owner. To assess the sustainability of these localised control efforts, this study investigates biological and management risk factors associated with trypanosome infections detected by polymerase chain reaction (PCR), in a range of domestic livestock at the local scale in Busia, Kenya. Busia District also remains endemic for human sleeping sickness with sporadic cases of sleeping sickness reported. Results In total, trypanosome infections were detected in 11.9% (329) out of the 2773 livestock sampled in Busia District. Multivariable logistic regression revealed that host species and cattle age affected overall trypanosome infection, with significantly increased odds of infection for cattle older than 18 months, and significantly lower odds of infection in pigs and small ruminants. Different grazing and watering management practices did not affect the odds of trypanosome infection, adjusted by host species. Neither anaemia nor condition score significantly affected the odds of trypanosome infection in cattle. Human infective Trypanosoma brucei rhodesiense were detected in 21.5% of animals infected with T. brucei s.l. (29/135) amounting to 1% (29/2773) of all sampled livestock, with significantly higher odds of T. brucei rhodesiense infections in T. brucei s.l. infected pigs (OR = 4.3, 95%CI 1.5-12.0) than in T. brucei s.l. infected cattle or small ruminants. Conclusions Although cattle are the dominant reservoir of trypanosome infection it is unlikely that targeted treatment of only visibly diseased cattle will achieve sustainable interruption of transmission for either animal infective or zoonotic human infective trypanosomiasis, since most infections were detected in cattle that did not exhibit classical clinical signs of

  1. A computational method for prediction of matrix proteins in endogenous retroviruses.

    Science.gov (United States)

    Ma, Yucheng; Liu, Ruiling; Lv, Hongqiang; Han, Jiuqiang; Zhong, Dexing; Zhang, Xinman

    2017-01-01

    Human endogenous retroviruses (HERVs) encode active retroviral proteins, which may be involved in the progression of cancer and other diseases. Matrix protein (MA), in group-specific antigen genes (gag) of retroviruses, is associated with the virus envelope glycoproteins in most mammalian retroviruses and may be involved in virus particle assembly, transport and budding. However, the amount of annotated MAs in ERVs is still at a low level so far. No computational method to predict the exact start and end coordinates of MAs in gags has been proposed yet. In this paper, a computational method to identify MAs in ERVs is proposed. A divide and conquer technique was designed and applied to the conventional prediction model to acquire better results when dealing with gene sequences with various lengths. Initiation sites and termination sites were predicted separately and then combined according to their intervals. Three different algorithms were applied and compared: weighted support vector machine (WSVM), weighted extreme learning machine (WELM) and random forest (RF). G - mean (geometric mean of sensitivity and specificity) values of initiation sites and termination sites under 5-fold cross validation generated by random forest models are 0.9869 and 0.9755 respectively, highest among the algorithms applied. Our prediction models combine RF & WSVM algorithms to achieve the best prediction results. 98.4% of all the collected ERV sequences with complete MAs (125 in total) could be predicted exactly correct by the models. 94,671 HERV sequences from 118 families were scanned by the model, 104 new putative MAs were predicted in human chromosomes. Distributions of the putative MAs and optimizations of model parameters were also analyzed. The usage of our predicting method was also expanded to other retroviruses and satisfying results were acquired.

  2. A computational method for prediction of matrix proteins in endogenous retroviruses.

    Directory of Open Access Journals (Sweden)

    Yucheng Ma

    Full Text Available Human endogenous retroviruses (HERVs encode active retroviral proteins, which may be involved in the progression of cancer and other diseases. Matrix protein (MA, in group-specific antigen genes (gag of retroviruses, is associated with the virus envelope glycoproteins in most mammalian retroviruses and may be involved in virus particle assembly, transport and budding. However, the amount of annotated MAs in ERVs is still at a low level so far. No computational method to predict the exact start and end coordinates of MAs in gags has been proposed yet. In this paper, a computational method to identify MAs in ERVs is proposed. A divide and conquer technique was designed and applied to the conventional prediction model to acquire better results when dealing with gene sequences with various lengths. Initiation sites and termination sites were predicted separately and then combined according to their intervals. Three different algorithms were applied and compared: weighted support vector machine (WSVM, weighted extreme learning machine (WELM and random forest (RF. G - mean (geometric mean of sensitivity and specificity values of initiation sites and termination sites under 5-fold cross validation generated by random forest models are 0.9869 and 0.9755 respectively, highest among the algorithms applied. Our prediction models combine RF & WSVM algorithms to achieve the best prediction results. 98.4% of all the collected ERV sequences with complete MAs (125 in total could be predicted exactly correct by the models. 94,671 HERV sequences from 118 families were scanned by the model, 104 new putative MAs were predicted in human chromosomes. Distributions of the putative MAs and optimizations of model parameters were also analyzed. The usage of our predicting method was also expanded to other retroviruses and satisfying results were acquired.

  3. Human Immunodeficiency Virus Type 1 Infection of Neural Xenografts

    Science.gov (United States)

    Cvetkovich, Therese A.; Lazar, Eliot; Blumberg, Benjamin M.; Saito, Yoshihiro; Eskin, Thomas A.; Reichman, Richard; Baram, David A.; del Cerro, Coca; Gendelman, Howard E.; del Cerro, Manuel; Epstein, Leon G.

    1992-06-01

    Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.

  4. Humanized chimeric mouse models of hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Suwan Sun

    2017-06-01

    Full Text Available Hepatitis B virus (HBV infection is associated with an increased risk of hepatic cirrhosis, hepatocellular carcinoma, fulminant hepatitis and end-stage hepatic failure. Despite the availability of anti-HBV therapies, HBV infection remains a major global public health problem. Developing an ideal animal model of HBV infection to clarify the details of the HBV replication process, the viral life cycle, the resulting immunoresponse and the precise pathogenesis of HBV is difficult because HBV has an extremely narrow host range and almost exclusively infects humans. In this review, we summarize and evaluate animal models available for studying HBV infection, especially focusing on humanized chimeric mouse models, and we discuss future development trends regarding immunocompetent humanized mouse models that can delineate the natural history and immunopathophysiology of HBV infection.

  5. Oesophageal Ulceration in Human Immunodeficiency Virus Infected ...

    African Journals Online (AJOL)

    Objective. To determine the aetiology of oesophageal ulceration in HIV-infected patients. Design. A retrospective clinical, endoscopic and histopathological analysis of patients with confirmed HIV infection and an oesophageal ulcer diagnosed on endoscopy. Setting. A tertiary referral, gastrointestinal clinic in Cape Town.

  6. Human cytomegalovirus infections in premature infants by ...

    African Journals Online (AJOL)

    Freezing breast milk may be protective for the preterm infant until the titer of CMV antibody increases. However clinical importance of CMV infection in premature infants by breast-feeding is still unclear. This minireview focuses on recent advances in the study of CMV infection in premature infants by breastfeeding.

  7. Laboratory diagnosis of persistent human chlamydial infection

    Directory of Open Access Journals (Sweden)

    Mirja ePuolakkainen

    2013-12-01

    Full Text Available Diagnostic assays for persistent chlamydial infection are much needed to conduct high-quality, large-scale studies investigating the persistent state in vivo, its disease associations and the response to therapy. Yet in most studies the distinction between acute and persistent infection is based on the interpretation of the data obtained by the assays developed to diagnose acute infections or on complex assays available for research only and/or difficult to establish for clinical use. Novel biomarkers for detection of persistent chlamydial infection are urgently needed. Chlamydial whole genome proteome arrays are now available and they can identify chlamydial antigens that are differentially expressed between acute infection and persistent infection. Utilizing these data will lead to the development of novel diagnostic assays. Carefully selected specimens from well-studied patient populations are clearly needed in the process of translating the proteomic data into assays useful for clinical practice. Before such antigens are identified and validated assays become available, we face a challenge of deciding whether the persistent infection truly induced appearance of the proposed marker or do we just base our diagnosis of persistent infection on the presence of the suggested markers. Consequently, we must bear this in mind when interpreting the available data.

  8. Human immunodeficiency virus (HIV) infection in tuberculosis ...

    African Journals Online (AJOL)

    BACKGROUND: In a country with a rapidly spreading HIV epidemic information regarding HIV and TB Co-infection are lacking. OBJECTIVES: To determine the prevalence of HIV infection in a representative sample of sputum-positive tuberculosis patients. METHODS: A cross-sectional survey whereby blood sample was ...

  9. Capsid-binding retrovirus restriction factors: discovery, restriction specificity and implications for the development of novel therapeutics.

    Science.gov (United States)

    Sanz-Ramos, Marta; Stoye, Jonathan P

    2013-12-01

    The development of drugs against human immunodeficiency virus type 1 infection has been highly successful, and numerous combinational treatments are currently available. However, the risk of the emergence of resistance and the toxic effects associated with prolonged use of antiretroviral therapies have emphasized the need to consider alternative approaches. One possible area of investigation is provided by the properties of restriction factors, cellular proteins that protect organisms against retroviral infection. Many show potent viral inhibition. Here, we describe the discovery, properties and possible therapeutic uses of the group of restriction factors known to interact with the capsid core of incoming retroviruses. This group comprises Fv1, TRIM5α and TRIMCypA: proteins that all act shortly after virus entry into the target cell and block virus replication at different stages prior to integration of viral DNA into the host chromosome. They have different origins and specificities, but share general structural features required for restriction, with an N-terminal multimerization domain and a C-terminal capsid-binding domain. Their overall efficacy makes it reasonable to ask whether they might provide a framework for developing novel antiretroviral strategies.

  10. [Cerebellar syndrome and peripheral neuropathy as manifestations of infection by HTLV-1 human T-cell lymphotropic virus].

    Science.gov (United States)

    Carod-Artal, F J; del Negro, M C; Vargas, A P; Rizzo, I

    Type I human T-cell lymphotropic virus (HTLV-I) is a retrovirus with affinity for CD4 cells. This infection may give rise to a broad spectrum of disorders including T-cell leucemia/lymphoma, the myelopathy/tropical spastic paraparesis complex (M/TSP), and to a lesser extent, uveitis, arthritis, polymyositis and peripheral neuropathy. M/TSP is a progressive, chronic myelopathy characterized by spasticity, hypereflexia, muscle weakness and sphincter disorders. Much less frequently it may precede, or give rise to, a cerebellar syndrome with ataxia and intention tremor. We describe the case of a 13 year old adolescent girl who presented with a neurological syndrome which had started with tremor of the head and limbs, ataxia, dysmetria, frequent falls and sphincter disorders. During the two and a half years that she had had this illness she had developed spastic paraparesis of the legs and had repeated urinary infections. Serology of blood and CSF was positive for HTLV-I using the ELISA technique and confirmed by Western-blot. EMG showed predominantly axonal sensomotor neuropathy. A neurogenic bladder was detected on functional urodynamic studies. On MR there was moderate atrophy of the thoracic spinal cord and slight alterations of the subcortical white matter. The presence of a cerebellar syndrome or neuropathy of uncertain origin, in endemic areas, should lead to the inclusion of HTLV-I infection in the differential diagnosis, even in the absence of pyramidal symptoms or defined M/TSP. Maternal seropositivity supports the hypothesis of mother-daughter transmission during lactation.

  11. Impact of cell culture process changes on endogenous retrovirus expression.

    Science.gov (United States)

    Brorson, Kurt; De Wit, Christina; Hamilton, Elizabeth; Mustafa, Mehnaz; Swann, Patrick G; Kiss, Robert; Taticek, Ron; Polastri, Gian; Stein, Kathryn E; Xu, Yuan

    2002-11-05

    Cell culture process changes (e.g., changes in scale, medium formulation, operational conditions) and cell line changes are common during the development life cycle of a therapeutic protein. To ensure that the impact of such process changes on product quality and safety is minimal, it is standard practice to compare critical product quality and safety attributes before and after the changes. One potential concern introduced by cell culture process improvements is the possibility of increased endogenous retrovirus expression to a level above the clearance capability of the subsequent purification process. To address this, retrovirus expression was measured in scaled down and full production scaled Chinese hamster ovary (CHO) cell cultures of four monoclonal antibodies and one recombinant protein before and after process changes. Two highly sensitive, quantitative (Q)-PCR-based assays were used to measure endogenous retroviruses. It is shown that cell culture process changes that primarily alter media components, nutrient feed volume, seed density, cell bank source (i.e., master cell bank vs. working cell bank), and vial size, or culture scale, singly or in combination, do not impact the rate of retrovirus expression to an extent greater than the variability of the Q-PCR assays (0.2-0.5 log(10)). Cell culture changes that significantly alter the metabolic state of the cells and/or rates of protein expression (e.g., pH and temperature shifts, NaButyrate addition) measurably impact the rate of retrovirus synthesis (up to 2 log(10)). The greatest degree of variation in endogenous retrovirus expression was observed between individual cell lines (up to 3 log(10)). These data support the practice of measuring endogenous retrovirus output for each new cell line introduced into manufacturing or after process changes that significantly increase product-specific productivity or alter the metabolic state, but suggest that reassessment of retrovirus expression after other

  12. Human muscle satellite cells as targets of Chikungunya virus infection.

    Directory of Open Access Journals (Sweden)

    Simona Ozden

    Full Text Available BACKGROUND: Chikungunya (CHIK virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. Since 2005, the emergence of CHIK virus was associated with an unprecedented magnitude outbreak of CHIK disease in the Indian Ocean. Clinically, this outbreak was characterized by invalidating poly-arthralgia, with myalgia being reported in 97.7% of cases. Since the cellular targets of CHIK virus in humans are unknown, we studied the pathogenic events and targets of CHIK infection in skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistology on muscle biopsies from two CHIK virus-infected patients with myositic syndrome showed that viral antigens were found exclusively inside skeletal muscle progenitor cells (designed as satelllite cells, and not in muscle fibers. To evaluate the ability of CHIK virus to replicate in human satellite cells, we assessed virus infection on primary human muscle cells; viral growth was observed in CHIK virus-infected satellite cells with a cytopathic effect, whereas myotubes were essentially refractory to infection. CONCLUSIONS/SIGNIFICANCE: This report provides new insights into CHIK virus pathogenesis, since it is the first to identify a cellular target of CHIK virus in humans and to report a selective infection of muscle satellite cells by a viral agent in humans.

  13. Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells.

    Science.gov (United States)

    Mayer, Bryan T; Krantz, Elizabeth M; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T; Gantt, Soren

    2017-06-15

    Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine. IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We

  14. Severe respiratory tract infections with human bocavirus in children

    Directory of Open Access Journals (Sweden)

    Halise Akça, Nilden Tuygun, Emine Polat, Can Demir Karacan

    2016-09-01

    Full Text Available Acute respiratory tract infection remains a major cause of childhood hospitalization and mortality in young children. Human bocavirus (HBoV is a virus belonging to the Parvoviridae family, which has been newly discovered to be associated with respiratory tract infection in children. Human bocavirus infection is usually seen as form of co-infection. The frequent associations of HBoV with other respiratory viruses might be explained by the persistence of HBoV in the respiratory tract. HBoV primary events generally associated with mild respiratory illness. Here, we reported three patients who developed an extremely severe acute life-threatening respiratory failure due to HBoV infection. J Microbiol Infect Dis 2016; 6(3: 145-147

  15. Immune Modulation in Primary Vaccinia virus Zoonotic Human Infections

    Directory of Open Access Journals (Sweden)

    Juliana Assis Silva Gomes

    2012-01-01

    Full Text Available In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, including Monkeypox, Cowpox, and Vaccinia virus (VACV. Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4+ cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans.

  16. Acute Disseminated Encephalomyelitis After Human Parechovirus Infection.

    Science.gov (United States)

    Obermeier, Patrick E; Karsch, Katharina; Hoppe, Christian; Seeber, Lea; Schneider, Joanna; Mühlhans, Susann; Chen, Xi; Tief, Franziska; Kaindl, Angela M; Weschke, Bernhard; Böttcher, Sindy; Diedrich, Sabine; Rath, Barbara

    2016-01-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory, demyelinating disease occurring several weeks after viral infection. Enteroviruses have been described as potential triggers of ADEM, but the closely related parechoviruses have not. The objective of the study is to assess the prevalence and disease presentation of ADEM after parechovirus infection in a syndromic surveillance program for pediatric infection/inflammation of the central nervous system (CNS). The surveillance was conducted at the Charité Department of Pediatrics in Berlin, Germany, from November 2010 to November 2014. All hospitalized children meeting predefined case criteria underwent highly standardized prospective clinical assessments based on the published case definitions, including for ADEM. Stool samples were independently analyzed by enterovirus and parechovirus real-time polymerase chain reaction at the Robert Koch Institute. Of 105,557 patients screened, 774 (0.7%) fulfilled entry criteria for CNS infection/inflammation, with 114 cases ascertained as ADEM. Parechoviruses were detected in 2.5% of patients with CNS infection/inflammation, including 1 case fulfilling ADEM case criteria with the highest level of diagnostic certainty. We report a first case of ADEM after parechovirus infection in a 5-year-old female presenting with acute hemiparesis 2 weeks after a respiratory illness. Parechovirus disease should be included in the differential diagnosis of ADEM.

  17. Retrovirus Epidemiology Donor Study-II (REDS-II)

    Science.gov (United States)

    2016-04-14

    Acquired Immunodeficiency Syndrome; Blood Donors; Blood Transfusion; HIV Infections; HIV-1; HIV-2; HTLV-I; HTLV-II; Retroviridae Infections; Hepatitis, Viral, Human; Hepatitis B; Hepacivirus; West Nile Virus

  18. No evidence for ape Plasmodium infections in humans in Gabon.

    Science.gov (United States)

    Délicat-Loembet, Lucresse; Rougeron, Virginie; Ollomo, Benjamin; Arnathau, Céline; Roche, Benjamin; Elguero, Eric; Moukodoum, Nancy Diamella; Okougha, Alain-Prince; Mve Ondo, Bertrand; Boundenga, Larson; Houzé, Sandrine; Galan, Maxime; Nkoghé, Dieudonné; Leroy, Eric M; Durand, Patrick; Paupy, Christophe; Renaud, François; Prugnolle, Franck

    2015-01-01

    African great apes are naturally infected by a multitude of Plasmodium species most of them recently discovered, among which several are closely related to human malaria agents. However, it is still unknown whether these animals can serve as source of infections for humans living in their vicinity. To evaluate this possibility, we analysed the nature of Plasmodium infections from a bank of 4281 human blood samples collected in 210 villages of Gabon, Central Africa. Among them, 2255 were detected positive to Plasmodium using molecular methods (Plasmodium Cytochrome b amplification). A high throughput sequencing technology (454 GS-FLX Titanium technology, Roche) was then used to identify the Plasmodium species present within each positive sample. Overall, we identified with confidence only three species infecting humans in Gabon: P. falciparum, P. malariae and P. ovale. None of the species known to infect non-human primates in Central Africa was found. Our study shows that ape Plasmodium parasites of the subgenus Laverania do not constitute a frequent source of infection for humans. It also suggests that some strong host genetic barriers must exist to prevent the cross species transmission of ape Plasmodium in a context of ever increasing contacts between humans and wildlife.

  19. Tracking interspecies transmission and long-term evolution of an ancient retrovirus using the genomes of modern mammals.

    Science.gov (United States)

    Diehl, William E; Patel, Nirali; Halm, Kate; Johnson, Welkin E

    2016-03-08

    Mammalian genomes typically contain hundreds of thousands of endogenous retroviruses (ERVs), derived from ancient retroviral infections. Using this molecular 'fossil' record, we reconstructed the natural history of a specific retrovirus lineage (ERV-Fc) that disseminated widely between ~33 and ~15 million years ago, corresponding to the Oligocene and early Miocene epochs. Intercontinental viral spread, numerous instances of interspecies transmission and emergence in hosts representing at least 11 mammalian orders, and a significant role for recombination in diversification of this viral lineage were also revealed. By reconstructing the canonical retroviral genes, we identified patterns of adaptation consistent with selection to maintain essential viral protein functions. Our results demonstrate the unique potential of the ERV fossil record for studying the processes of viral spread and emergence as they play out across macro-evolutionary timescales, such that looking back in time may prove insightful for predicting the long-term consequences of newly emerging viral infections.

  20. Primary and secondary infection with human parvovirus B19 in ...

    African Journals Online (AJOL)

    Primary and secondary infection with human parvovirus. B19 in pregnant women in South Africa ... I Infection during pregnancy may lead to fetal loss, especially during the second trimester, because of severe ... IgG antibodies) with viruses such as rubella: cyto- megalovirus' and varicella." Subjects and methods. A total of 1 ...

  1. Human papillomavirus infection and disease in men: Impact of HIV

    African Journals Online (AJOL)

    2 London School of Hygiene and Tropical Medicine, London, United Kingdom. Corresponding author: S Delany-Moretlwe (sdelany@wrhi.ac.za). Human papillomavirus (HPV) is a common sexually transmitted infection (STI) affecting both men and women.[1] HPV infections can be classified as either low- (LR) or high-risk ...

  2. Knowledge of Human Papillomavirus Infection and Acceptability of ...

    African Journals Online (AJOL)

    Introduction: Human papillomavirus (HPV) is one of the most common sexually transmitted infections and has been implicated in over 70% of cases of cervical cancer. This study assessed the knowledge of HPV infection and acceptability of HPV vaccination among nursing students in Benin City. Methodology: A ...

  3. Adenovirus infection reverses the antiviral state induced by human interferon.

    Science.gov (United States)

    Feduchi, E; Carrasco, L

    1987-04-06

    HeLa cells treated with human lymphoblastoid interferon do not synthesize poliovirus proteins. The antiviral state against poliovirus is reversed if cells are previously infected with adenovirus type 5. A late gene product seems to be involved in this reversion, since no effect is observed at early stages of infection or in the presence of aphidicolin.

  4. Cardiovascular implications from untreated human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Baker, Jason V; Lundgren, Jens D

    2011-01-01

    Atherosclerotic cardiovascular disease (CVD) has become an important cause of morbidity and mortality among individuals with human immunodeficiency virus (HIV) infection with access to antiretroviral medications, as the risk for AIDS has fallen and life expectancy improved. Traditional CVD risk...

  5. malaria parasitaemia among febrile children infected with human

    African Journals Online (AJOL)

    2014-01-01

    Jan 1, 2014 ... MALARIA PARASITAEMIA AMONG FEBRILE CHILDREN INFECTED WITH. HUMAN IMMUNODEFICIENCY VIRUS IN THE CONTEXT OF PROPHYLACTIC. COTRIMOXAZOLE AS STANDARD OF CARE: A CROSS- SECTIONAL SURVEY. IN WESTERN KENYA. I. K. MARETE, M. MUTUGI, Z. LAGAT, ...

  6. Human immunodeficiency virus infection presenting as a fatal case ...

    African Journals Online (AJOL)

    MJP

    2015-06-25

    CMV), Epstein-. Barr virus (EBV), Hepatitis B and C virus,. Mycoplasma. Pneumoniae,. Haemophilus influenzae and Campylobacter jejuni have all been implicated in. GBS.[6]. Human immunodeficiency virus (HIV) infection has ...

  7. RSV Infection in Human Macrophages Promotes CXCL10/IP-10 Expression during Bacterial Co-Infection

    Directory of Open Access Journals (Sweden)

    Daniela Machado

    2017-12-01

    Full Text Available Respiratory syncytial virus (RSV, a major etiologic agent of acute lower respiratory infection constitutes the most important cause of death in young children worldwide. Viral/bacterial mixed infections are related to severity of respiratory inflammatory diseases, but the underlying mechanisms remain poorly understood. We have previously investigated the intracellular mechanisms that mediate the immune response in the context of influenza virus/Streptococcus pneumoniae (Sp co-infection using a model of human monocyte-derived macrophages (MDMs. Here, we set up and characterized a similar model of MDMs to investigate different scenarios of RSV infection and co-infection with Sp. Our results suggest that Sp contributes to a faster and possibly higher level of CXCL10/IP-10 expression induced by RSV infection in human MDMs.

  8. A DNA Vaccine Protects Human Immune Cells against Zika Virus Infection in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Guohua Yi

    2017-11-01

    Full Text Available A DNA vaccine encoding prM and E protein has been shown to induce protection against Zika virus (ZIKV infection in mice and monkeys. However, its effectiveness in humans remains undefined. Moreover, identification of which immune cell types are specifically infected in humans is unclear. We show that human myeloid cells and B cells are primary targets of ZIKV in humanized mice. We also show that a DNA vaccine encoding full length prM and E protein protects humanized mice from ZIKV infection. Following administration of the DNA vaccine, humanized DRAG mice developed antibodies targeting ZIKV as measured by ELISA and neutralization assays. Moreover, following ZIKV challenge, vaccinated animals presented virtually no detectable virus in human cells and in serum, whereas unvaccinated animals displayed robust infection, as measured by qRT-PCR. Our results utilizing humanized mice show potential efficacy for a targeted DNA vaccine against ZIKV in humans.

  9. Contribution of the Retrovirus Epidemiology Donor Study (REDS to research on blood transfusion safety in Brazil

    Directory of Open Access Journals (Sweden)

    Paula Loureiro

    2014-04-01

    Full Text Available The Retrovirus Epidemiology Donor Study (REDS program was established in the United States in 1989 with the purpose of increasing blood transfusion safety in the context of the HIV/AIDS and human T-lymphotropic virus epidemics. REDS and its successor, REDS-II were at first conducted in the US, then expanded in 2006 to include international partnerships with Brazil and China. In 2011, a third wave of REDS renamed the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III was launched. This seven-year research program focuses on both blood banking and transfusion medicine research in the United States of America, Brazil, China, and South Africa. The main goal of the international programs is to reduce and prevent the transmission of HIV/AIDS and other known and emerging infectious agents through transfusion, and to address research questions aimed at understanding global issues related to the availability of safe blood. This article describes the contribution of REDS-II to transfusion safety in Brazil. Articles published from 2010 to 2013 are summarized, including database analyses to characterize blood donors, deferral rates, and prevalence, incidence and residual risk of the main blood-borne infections. Specific studies were developed to understand donor motivation, the impact of the deferral questions, risk factors and molecular surveillance among HIV-positive donors, and the natural history of Chagas disease. The purpose of this review is to disseminate the acquired knowledge and briefly summarize the findings of the REDS-II studies conducted in Brazil as well as to introduce the scope of the REDS-III program that is now in progress and will continue through 2018.

  10. Milk Oligosaccharides Inhibit Human Rotavirus Infectivity in MA104 Cells.

    Science.gov (United States)

    Laucirica, Daniel R; Triantis, Vassilis; Schoemaker, Ruud; Estes, Mary K; Ramani, Sasirekha

    2017-09-01

    Background: Oligosaccharides in milk act as soluble decoy receptors and prevent pathogen adhesion to the infant gut. Milk oligosaccharides reduce infectivity of a porcine rotavirus strain; however, the effects on human rotaviruses are less well understood. Objective: In this study, we determined the effect of specific and abundant milk oligosaccharides on the infectivity of 2 globally dominant human rotavirus strains. Methods: Four milk oligosaccharides-2'-fucosyllactose (2'FL), 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), and galacto-oligosaccharides-were tested for their effects on the infectivity of human rotaviruses G1P[8] and G2P[4] through fluorescent focus assays on African green monkey kidney epithelial cells (MA104 cells). Oligosaccharides were added at different time points in the infectivity assays. Infections in the absence of oligosaccharides served as controls. Results: When compared with infections in the absence of glycans, all oligosaccharides substantially reduced the infectivity of both human rotavirus strains in vitro; however, virus strain-specific differences in effects were observed. Compared with control infections, the maximum reduction in G1P[8] infectivity was seen with 2'FL when added after the onset of infection (62% reduction, P < 0.01), whereas the maximum reduction in G2P[4] infectivity was seen with the mixture of 3'SL + 6'SL when added during infection (73% reduction, P < 0.01). The mixture of 3'SL + 6'SL at the same ratio as is present in breast milk was more potent in reducing G2P[4] infectivity (73% reduction, P < 0.01) than when compared with 3'SL (47% reduction) or 6'SL (40% reduction) individually. For all oligosaccharides the reduction in infectivity was mediated by an effect on the virus and not on the cells. Conclusions: Milk oligosaccharides reduce the infectivity of human rotaviruses in MA104 cells, primarily through an effect on the virus. Although breastfed infants are directly protected, the addition of specific

  11. 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...

  12. Update on human immunodeficiency virus (HIV)-2 infection.

    Science.gov (United States)

    Campbell-Yesufu, Omobolaji T; Gandhi, Rajesh T

    2011-03-15

    Infection with human immunodeficiency virus type 2 (HIV-2) occurs mainly in West Africa, but an increasing number of cases have been recognized in Europe, India, and the United States. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we present information on recent clinical advances in our understanding of HIV-2 infection and highlight remaining diagnostic and therapeutic challenges.

  13. Prevalence of koala retrovirus in geographically diverse populations in Australia.

    Science.gov (United States)

    Simmons, G S; Young, P R; Hanger, J J; Jones, K; Clarke, D; McKee, J J; Meers, J

    2012-10-01

    To determine the prevalence of koala retrovirus (KoRV) in selected koala populations and to estimate proviral copy number in a subset of koalas. Blood or tissue samples from 708 koalas in Queensland, New South Wales, Victoria and South Australia were tested for KoRV pol provirus gene using standard polymerase chain reaction (PCR), nested PCR and real-time PCR (qPCR). Prevalence of KoRV provirus-positive koalas was 100% in four regions of Queensland and New South Wales, 72.2% in mainland Victoria, 26.6% on four Victorian islands and 14.8% on Kangaroo Island, South Australia. Estimated proviral copy number per cell in four groups of koalas from Queensland and Victoria showed marked variation, ranging from a mean of 165 copies per cell in the Queensland group to 1.29 × 10(-4) copies per cell in one group of Victorian koalas. The higher prevalence of KoRV-positive koalas in the north of Australia and high proviral loads in Queensland koalas may indicate KoRV entered and became endogenous in the north and is spreading southwards. It is also possible there are genetic differences between koalas in northern and southern Australia that affect susceptibility to KoRV infection or endogenisation, or that environmental factors affecting transmission in northern states are absent or uncommon in southern regions. Although further studies are required, the finding of proviral copy numbers orders of magnitude lower than what would be expected for the presence of a single copy in every cell for many Victorian animals suggests that KoRV is not endogenous in these animals and likely reflects ongoing exogenous infection. © 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.

  14. Neopterin and human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Hofmann, B

    1993-01-01

    to predict the later development of AIDS. The increased neopterin concentrations show that the immune system is activated in HIV infection and demonstrate the presence of an interaction between the virus and the immune system. The most important future use of neopterin measurements may be in fast evaluation...

  15. Brucella neotomae Infection in Humans, Costa Rica.

    Science.gov (United States)

    Suárez-Esquivel, Marcela; Ruiz-Villalobos, Nazareth; Jiménez-Rojas, César; Barquero-Calvo, Elías; Chacón-Díaz, Carlos; Víquez-Ruiz, Eunice; Rojas-Campos, Norman; Baker, Kate S; Oviedo-Sánchez, Gerardo; Amuy, Ernesto; Chaves-Olarte, Esteban; Thomson, Nicholas R; Moreno, Edgardo; Guzmán-Verri, Caterina

    2017-06-01

    Several species of Brucella are known to be zoonotic, but B. neotomae infection has been thought to be limited to wood rats. In 2008 and 2011, however, B. neotomae was isolated from cerebrospinal fluid of 2 men with neurobrucellosis. The nonzoonotic status of B. neotomae should be reassessed.

  16. Avian Influenza Infection in Humans

    African Journals Online (AJOL)

    Pulmonology Unit, Department of Medicine,. University College Hospital, Ibadan. INTRODUCTION _ ... saliva, nasal secretions and faeces. Susceptible birds become infected when they have contact with con- .... ing and immunofluorescence[l4, 1 5]. Laboratory tests are required for specific identification of avian. influenza.

  17. Pan-vertebrate comparative genomics unmasks retrovirus macroevolution.

    Science.gov (United States)

    Hayward, Alexander; Cornwallis, Charlie K; Jern, Patric

    2015-01-13

    Although extensive research has demonstrated host-retrovirus microevolutionary dynamics, it has been difficult to gain a deeper understanding of the macroevolutionary patterns of host-retrovirus interactions. Here we use recent technological advances to infer broad patterns in retroviral diversity, evolution, and host-virus relationships by using a large-scale phylogenomic approach using endogenous retroviruses (ERVs). Retroviruses insert a proviral DNA copy into the host cell genome to produce new viruses. ERVs are provirus insertions in germline cells that are inherited down the host lineage and consequently present a record of past host-viral associations. By mining ERVs from 65 host genomes sampled across vertebrate diversity, we uncover a great diversity of ERVs, indicating that retroviral sequences are much more prevalent and widespread across vertebrates than previously appreciated. The majority of ERV clades that we recover do not contain known retroviruses, implying either that retroviral lineages are highly transient over evolutionary time or that a considerable number of retroviruses remain to be identified. By characterizing the distribution of ERVs, we show that no major vertebrate lineage has escaped retroviral activity and that retroviruses are extreme host generalists, having an unprecedented ability for rampant host switching among distantly related vertebrates. In addition, we examine whether the distribution of ERVs can be explained by host factors predicted to influence viral transmission and find that internal fertilization has a pronounced effect on retroviral colonization of host genomes. By capturing the mode and pattern of retroviral evolution and contrasting ERV diversity with known retroviral diversity, our study provides a cohesive framework to understand host-virus coevolution better.

  18. Genital human papillomavirus infection in Panama City prostitutes.

    Science.gov (United States)

    Reeves, W C; Arosemena, J R; Garcia, M; de Lao, S L; Cuevas, M; Quiroz, E; Caussy, D; Rawls, W E

    1989-10-01

    Little is known of the natural history of genital human papillomavirus (HPV) infections in women from high-risk populations. Samples were collected from 183 Panama City prostitutes and assessed for HPV (filter in situ DNA hybridization) and for sexually transmitted agents. The cohort was followed for 8 mo; 51% of subjects completed four monthly return visits and 16% were sampled eight times. The proportion of women found infected with HPV increased significantly with increasing numbers of consecutive samples tested; 38 (21%) of 183 women were positive after one visit and 46 (82%) of 56 who completed six visits were infected. The pattern of viral detection over time was not random, which implied that most prostitutes were persistently infected with genital HPVs and that either scattered foci of infection or periodic reactivation of latent virus occurred. Our findings suggest that multiple sampling is necessary to accurately estimate HPV infection rates and to define whether patterns of DNA expression are present.

  19. Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

    Science.gov (United States)

    Bonnafous, Pascale; Gautheret-Dejean, Agnès

    2015-01-01

    SUMMARY Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and

  20. PREVALENCE OF INFECTION WITH HUMAN HERPESVIRUS ...

    African Journals Online (AJOL)

    were tuberculosis suspects but had no active STD (25 women and 25 men), 50 patients with a proven STD, and 36 paediatric inpatients ~th a variety of .... Frottier J. Detection of human herpesvirus 8 DNA sequences before the appearance of Kaposi's sarcoma in human immunodeficiency virus (HIV}-positive subjects with a ...

  1. West Nile Virus: Biology, Transmission, and Human Infection

    Science.gov (United States)

    Colpitts, Tonya M.; Conway, Michael J.; Montgomery, Ruth R.

    2012-01-01

    Summary: West Nile Virus was introduced into the Western Hemisphere during the late summer of 1999 and has been causing significant and sometimes severe human diseases since that time. This article briefly touches upon the biology of the virus and provides a comprehensive review regarding recent discoveries about virus transmission, virus acquisition, and human infection and disease. PMID:23034323

  2. Human Dobrava-Belgrade hantavirus infection, Kosovo.

    Science.gov (United States)

    Emmerich, Petra; Müller, Nicole; Heinemann, Patrick; Rother, Enno; Jakupi, Xhevat; Günther, Stephan; Cadar, Daniel; Schmidt-Chanasit, Jonas

    2014-11-01

    Here we describe an acute Dobrava-Belgrade virus (DOBV) infection that presented as severe hemorrhagic fever with renal syndrome (HFRS) in an active-duty U.S. soldier. The infection was acquired in northern Kosovo in spring 2013. Amplification of DOBV genome segments directly from the patient's serum sample was successfully performed. Phylogenetic analysis demonstrated that the strain belong to DOBV genotype Dobrava and is closely related to strains circulating in Southeast Europe and Slovakia. Thus, our case confirms that DOBV genotype Dobrava is able to cause a severe form of HFRS, especially when compared to the other less pathogenic DOBV genotypes. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Four Human Cases of Diphyllobothrium latum Infection

    Science.gov (United States)

    Choi, Hee-Jung; Lee, Junghye

    2012-01-01

    Diphyllobothrium latum infections in 4 young Korean men detected from 2008 to 2012 are presented. Three were diagnosed based on spontaneously discharged strobila of the adult worm in their feces, and 1 case was diagnosed by finding the worm at colonoscopy examination in a local clinic. The morphologic characteristics of the gravid proglottid and eggs were consistent with D. latum. All patients were treated with praziquantel 15 mg/kg, and follow-up stool examinations were done at 2 months after the medication. The main clinical complaints were intermittent gastrointestinal troubles such as indigestion, abdominal distension, and spontaneous discharge of tapeworm's segments in their feces. The most probable source of infection was the flesh of salmon or trout according to a patient's past history. These are the 45th to 48th recorded cases diagnosed by the adult worm in the Republic of Korea since 1971. PMID:22711926

  4. Mycobacterium abscessus Complex Infections in Humans.

    Science.gov (United States)

    Lee, Meng-Rui; Sheng, Wang-Huei; Hung, Chien-Ching; Yu, Chong-Jen; Lee, Li-Na; Hsueh, Po-Ren

    2015-09-01

    Mycobacterium abscessus complex comprises a group of rapidly growing, multidrug-resistant, nontuberculous mycobacteria that are responsible for a wide spectrum of skin and soft tissue diseases, central nervous system infections, bacteremia, and ocular and other infections. M. abscessus complex is differentiated into 3 subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. The 2 major subspecies, M. abscessus subsp. abscessus and M. abscessus subsp. massiliense, have different erm(41) gene patterns. This gene provides intrinsic resistance to macrolides, so the different patterns lead to different treatment outcomes. M. abscessus complex outbreaks associated with cosmetic procedures and nosocomial transmissions are not uncommon. Clarithromycin, amikacin, and cefoxitin are the current antimicrobial drugs of choice for treatment. However, new treatment regimens are urgently needed, as are rapid and inexpensive identification methods and measures to contain nosocomial transmission and outbreaks.

  5. Salmonella, a cross-kingdom pathogen infecting humans and plants.

    Science.gov (United States)

    Hernández-Reyes, Casandra; Schikora, Adam

    2013-06-01

    Infections with non-typhoidal Salmonella strains are constant and are a non-negligible threat to the human population. In the last two decades, salmonellosis outbreaks have increasingly been associated with infected fruits and vegetables. For a long time, Salmonellae were assumed to survive on plants after a more or less accidental infection. However, this notion has recently been challenged. Studies on the infection mechanism in vegetal hosts, as well as on plant immune systems, revealed an active infection process resembling in certain features the infection in animals. On one hand, Salmonella requires the type III secretion systems to effectively infect plants and to suppress their resistance mechanisms. On the other hand, plants recognize these bacteria and react to the infection with an induced defense mechanism similar to the reaction to other plant pathogens. In this review, we present the newest reports on the interaction between Salmonellae and plants. We discuss the possible ways used by these bacteria to infect plants as well as the plant responses to the infection. The recent findings indicate that plants play a central role in the dissemination of Salmonella within the ecosystem. © 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  6. Potential Therapy for Neisseria Gonorrhoeae Infections With Human Chorionic Gonadotropin.

    Science.gov (United States)

    Rao, C V

    2015-12-01

    The scientific evidence suggests that Neisseria gonorrhoeae (NG) infects human fallopian tubes by molecular mimicry in which pathogens act like a ligand to bind to epithelial cell surface human chorionic gonadotrophin (hCG)/luteinizing hormone (LH) receptors. The hCG-like molecule has been identified as ribosomal protein L12 in NG coat surface. Human fallopian tube epithelial cells have been shown to contain functional hCG/LH receptors. As previously shown in human fallopian tube organ and cell culture studies, cellular invasion and infection can be prevented by exposing the cells to excess hCG, which would outnumber and outcompete NG for receptor binding. Based on these data, we suggest testing hCG in clinical trials on infected women. © The Author(s) 2015.

  7. 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.

  8. 75 FR 79006 - Submission for OMB Review; Comment Request; Transfusion-Transmitted Retrovirus and Hepatitis...

    Science.gov (United States)

    2010-12-17

    ...- Transmitted Retrovirus and Hepatitis Virus Rates and Risk Factors: Improving the Safety of the U.S. Blood...: Transfusion-transmitted retrovirus and hepatitis virus rates and risk factors: Improving the safety of the U.S...

  9. Detection of hemoplasma and Bartonella species and co-infection with retroviruses in cats subjected to a spaying/neutering program in Jaboticabal, SP, Brazil Detecção de hemoplasmas e Bartonella sp. e co-infecção com retrovírus em gatos submetidos a um programa de castração/esterilização em Jaboticabal, SP, Brasil

    Directory of Open Access Journals (Sweden)

    Caroline Plácidi de Bortoli

    2012-09-01

    Full Text Available Hemotrophic mycoplasmas and Bartonella species are important pathogens that circulate between cats and invertebrate hosts, occasionally causing diseases in humans. Nevertheless, there are few reports on occurrences of these agents in cats in Brazil. The present study aimed to detect the presence of hemoplasma and Bartonella DNA by means of PCR and sequencing. FIV antigens and anti-FeLV antibodies, were studied by using a commercial kit on blood and serum samples, respectively, among 46 cats that were sampled during a spaying/neutering campaign conducted in Jaboticabal, SP. Three (6.5% cats were positive for hemoplasmas: two (4.3% for 'Candidatus M. haemominutum' and one (2.2% for both M. haemofelis and 'Candidatus M. turicensis'. One of the two 'Candidatus M. haemominutum'-infected cats was also positive for FeLV antigens and showed antibodies for FIV. Two cats (4.3% were positive for B. henselae. One of them was also positive for FeLV antigens. Eight cats (17.4% were positive for FeLV, and just one (2.2% showed anti-FIV antibodies. Bartonella species and hemoplasmas associated with infection due to retroviruses can circulate among apparently healthy cats.Micoplasmas hemotróficos e espécies de Bartonella são importantes patógenos que circulam entre gatos e hospedeiros invertebrados, causando ocasionalmente doenças no homem. Apesar disto, poucos são os estudos acerca da ocorrência destes agentes entre gatos no Brasil. O presente estudo objetivou detectar o DNA de hemoplasmas e Bartonella sp. pela PCR e sequenciamento. Antígeno de FIV e anticorpos anti-FeLV foram estudados utilizando um "kit" comercial, em amostras de sangue e soro, respectivamente, de 46 gatos amostrados em uma campanha de castração em Jaboticabal, SP. Três gatos (6,5% foram positivos para hemoplasmas: dois (4,3% para 'Candidatus M. haemominutum' e um (2,2% para M. haemofelis and 'Candidatus M. turicensis'. Um dos gatos positivos para 'Candidatus M. haemominutum

  10. Immunopathogenesis of oropharyngeal candidiasis in human immunodeficiency virus infection.

    Science.gov (United States)

    de Repentigny, Louis; Lewandowski, Daniel; Jolicoeur, Paul

    2004-10-01

    Oropharyngeal and esophageal candidiases remain significant causes of morbidity in human immunodeficiency virus (HIV)-infected patients, despite the dramatic ability of antiretroviral therapy to reconstitute immunity. Notable advances have been achieved in understanding, at the molecular level, the relationships between the progression of HIV infection, the acquisition, maintenance, and clonality of oral candidal populations, and the emergence of antifungal resistance. However, the critical immunological defects which are responsible for the onset and maintenance of mucosal candidiasis in patients with HIV infection have not been elucidated. The devastating impact of HIV infection on mucosal Langerhans' cell and CD4(+) cell populations is most probably central to the pathogenesis of mucosal candidiasis in HIV-infected patients. However, these defects may be partly compensated by preserved host defense mechanisms (calprotectin, keratinocytes, CD8(+) T cells, and phagocytes) which, individually or together, may limit Candida albicans proliferation to the superficial mucosa. The availability of CD4C/HIV transgenic mice expressing HIV-1 in immune cells has provided the opportunity to devise a novel model of mucosal candidiasis that closely mimics the clinical and pathological features of candidal infection in human HIV infection. These transgenic mice allow, for the first time, a precise cause-and-effect analysis of the immunopathogenesis of mucosal candidiasis in HIV infection under controlled conditions in a small laboratory animal.

  11. Anal Human Papillomavirus Infection among HIV-Infected Men in Korea.

    Directory of Open Access Journals (Sweden)

    Chang Hun Lee

    Full Text Available Little is known about the epidemiology on human papillomavirus (HPV infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea.A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour.A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM and 68 from men who have sex with women (MSW. Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P < 0.001. High-risk HPV (HR-HPV prevalence was higher among MSM (47.4% than MSW (25.0%; P = 0.002. The HR-HPV types identified most frequently were HPV 16 (11%, HPV 18 (9.9%, and HPV 58 (5% in MSM, and HPV 58(11% and HPV 16 (8.9% in MSW. Prevalence of any HPV types in 9-valent vaccine types was higher among MSM than MSW (47.4% vs 22.1%. P = 0.001. Abnormal anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P < 0.001. In HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection.Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age.

  12. Aspergillus Sydowi Infection of Human Finger Nail

    Directory of Open Access Journals (Sweden)

    A K Barde

    1981-01-01

    Full Text Available A case of Aspergillus sydowi infection of left middle finger nail is described ′ The presence of fungal hypae with phialids and spores on direct microscopy as well as in culture, the colour of the sub-ungual mass of the nail resembling the colour of the fungus in, culture′ repeated isolations of A sydowi from the diseased tissue along with the absence of any established pathogenic species in the specimen are taken as evidences that this fungus was invading the nail tissue.

  13. Influenza A virus infection of human Schwann cells in vitro.

    Science.gov (United States)

    Levine, Joshua; Buchman, Craig A; Fregien, Nevis

    2003-01-01

    Sudden sensorineural hearing loss, vestibular neuronitis, vocal fold paralysis and Bell's palsy have been associated with a viral etiology, due to the infection of nerve cells. The goal of this research was to ascertain whether Schwann cells can support infection with human influenza A virus and thereby represent a plausible alternative site for virus-host interaction. Viral infection of Schwann cells may lead to secretion of inflammatory mediators, leukocyte recruitment, demyelination and nerve damage. Cultured human Schwann cells were exposed to human influenza A virus. Infection was assayed at various times post-inoculation (0, 24, 48 and 72 h) using light microscopy, immunocytochemistry and influenza A virus-specific reverse transcriptase polymerase chain reaction (RT-PCR). A group of unexposed cells served as controls. Following exposure to the virus, vacuolization, cellular expansion and detachment from the dish were seen as early as 24 h post-inoculation. The exposed cells demonstrated positive immunocytochemical staining for influenza A virus antigen at 24, 48 and 72 h. Using RT-PCR, a sharp rise in influenza A virus-specific mRNA was detected. Human Schwann cells can be infected with human influenza A virus. Further studies will assess the inflammatory response in this model.

  14. A new retroelement constituted by a natural alternatively spliced RNA of murine replication-competent retroviruses.

    Science.gov (United States)

    Houzet, Laurent; Battini, Jean Luc; Bernard, Eric; Thibert, Valerie; Mougel, Marylène

    2003-09-15

    Replication of simple retroviruses depends on the recruitment of a single large primary transcript toward splicing, transport/packaging and translation regulations. In this respect, we studied the novel SD' 4.4 kb RNA of murine leukemia retroviruses (MLV) which results from alternative splicing of the primary transcript. We showed that SD' RNA was required for optimal replication since expression of a pre-spliced SD' RNA trans-complemented the impaired infectivity of a SD'-defective mutant. We monitored the fate of this novel transcript throughout early and late events of the viral life cycle. SD' RNA was specifically incorporated into virions demonstrating that the unspliced RNA was not the unique viral RNA present in virions. Furthermore, SD' RNA was reverse transcribed and its DNA copy integrated into the host genome, thus constituting a new splice donor-associated retroelement (SDARE) in infected cells. Finally, we showed that SD' mRNA encoded a 50 kDa polyprotein, and to a lower extent an additional 60 kDa polyprotein, which harbored Gag and integrase domains.

  15. Loss of volunteer blood donors because of unconfirmed enzyme immunoassay screening results. Retrovirus Epidemiology Donor Study.

    Science.gov (United States)

    Ownby, H E; Korelitz, J J; Busch, M P; Williams, A E; Kleinman, S H; Gilcher, R O; Nourjah, P

    1997-02-01

    Blood donors who test repeatably reactive on enzyme immunoassay (EIA) and are not confirmed as positive are a continuing problem for blood banks. Units are discarded and donors are deferred, in spite of multiple studies indicating that such donors are very rarely infected with the transmissible agents. Few data are available, however, with which to evaluate whether the discarded units are more likely to come from particular demographic subgroups. The Retrovirus Epidemiology Donor Study database of over 2 million allogeneic whole-blood donations collected in the years 1991 through 1993 was utilized. The prevalence of false-positive and indeterminate test results within demographic subgroups was computed for antibodies to human immunodeficiency virus, hepatitis C virus, and human T-lymphotropic virus (anti-HIV, anti-HCV, anti-HTLV, respectively) and hepatitis B surface antigen (false-positive only) as the proportion of donations that were repeatably reactive on EIA but negative or indeterminate on the confirmatory or supplemental test. Several demographic groups with increased prevalence of false-positive and indeterminate anti-HIV results were the same females, younger age groups, blacks, and first-time donors. Likewise, many of the demographic subgroups with increased prevalence of false-positive and indeterminate anti-HCV results were similar: older age groups, non-whites, lower education levels, first-time donors, donors making directed donations, and donors who had received transfusions. For anti-HTLV, by contrast, the oldest group had the highest prevalence of false-positive results but the lowest prevalence of indeterminate results: blacks had the lowest prevalence of false positive results but the highest prevalence of indeterminate results. If units that test repeatably reactive on EIA but that are not confirmed as positive are almost always from individuals not infected with the virus in question, then these results indicate that there may be sex-, race

  16. HIV infection and HERV expression: a review

    NARCIS (Netherlands)

    van der Kuyl, Antoinette C.

    2012-01-01

    The human genome contains multiple copies of retrovirus genomes known as endogenous retroviruses (ERVs) that have entered the germ-line at some point in evolution. Several of these proviruses have retained (partial) coding capacity, so that a number of viral proteins or even virus particles are

  17. Growth in Agarose of Human Cells Infected with Cytomegalovirus

    Science.gov (United States)

    Lang, David J.; Montagnier, Luc; Latarjet, Raymond

    1974-01-01

    After infection by human cytomegalovirus (CMV), human diploid fibroblasts could grow in agarose medium for several generations. Clones of infected cells grew for weeks, although in every case they ultimately underwent lysis owing to the cytopathic effect of the virus. Virus was inoculated at high dilution and after UV irradiation in an effort to derive cells infected with noninfectious defective particles still capable of inducing cell stimulation. Dilute or irradiated virus occasionally yielded large colonies of replicating cells, although permanent transformation was not observed. One clone derived from UV-CMV-infected cells was passaged four times before undergoing lysis. During these passages the cells exhibited alterations in morphology and orientation. Images PMID:4367907

  18. Dynamics of the cellular metabolome during human cytomegalovirus infection.

    Directory of Open Access Journals (Sweden)

    Joshua Munger

    2006-12-01

    Full Text Available Viral replication requires energy and macromolecular precursors derived from the metabolic network of the host cell. Despite this reliance, the effect of viral infection on host cell metabolic composition remains poorly understood. Here we applied liquid chromatography-tandem mass spectrometry to measure the levels of 63 different intracellular metabolites at multiple times after human cytomegalovirus (HCMV infection of human fibroblasts. Parallel microarray analysis provided complementary data on transcriptional regulation of metabolic pathways. As the infection progressed, the levels of metabolites involved in glycolysis, the citric acid cycle, and pyrimidine nucleotide biosynthesis markedly increased. HCMV-induced transcriptional upregulation of specific glycolytic and citric acid cycle enzymes mirrored the increases in metabolite levels. The peak levels of numerous metabolites during infection far exceeded those observed during normal fibroblast growth or quiescence, demonstrating that HCMV markedly disrupts cellular metabolic homeostasis and institutes its own specific metabolic program.

  19. Immunopathogenesis of Oropharyngeal Candidiasis in Human Immunodeficiency Virus Infection

    OpenAIRE

    De Repentigny, Louis; Lewandowski, Daniel; Jolicoeur, Paul

    2004-01-01

    Oropharyngeal and esophageal candidiases remain significant causes of morbidity in human immunodeficiency virus (HIV)-infected patients, despite the dramatic ability of antiretroviral therapy to reconstitute immunity. Notable advances have been achieved in understanding, at the molecular level, the relationships between the progression of HIV infection, the acquisition, maintenance, and clonality of oral candidal populations, and the emergence of antifungal resistance. However, the critical i...

  20. Marine origin of retroviruses in the early Palaeozoic Era

    Science.gov (United States)

    Aiewsakun, Pakorn; Katzourakis, Aris

    2017-01-01

    Very little is known about the ancient origin of retroviruses, but owing to the discovery of their ancient endogenous viral counterparts, their early history is beginning to unfold. Here we report 36 lineages of basal amphibian and fish foamy-like endogenous retroviruses (FLERVs). Phylogenetic analyses reveal that ray-finned fish FLERVs exhibit an overall co-speciation pattern with their hosts, while amphibian FLERVs might not. We also observe several possible ancient viral cross-class transmissions, involving lobe-finned fish, shark and frog FLERVs. Sequence examination and analyses reveal two major lineages of ray-finned fish FLERVs, one of which had gained two novel accessory genes within their extraordinarily large genomes. Our phylogenetic analyses suggest that this major retroviral lineage, and therefore retroviruses as a whole, have an ancient marine origin and originated together with, if not before, their jawed vertebrate hosts >450 million years ago in the Ordovician period, early Palaeozoic Era.

  1. Biology and evolution of the endogenous koala retrovirus.

    Science.gov (United States)

    Tarlinton, R; Meers, J; Young, P

    2008-11-01

    Although endogenous retroviruses are ubiquitous features of all mammalian genomes, the process of initial germ line invasion and subsequent inactivation from a pathogenic element has not yet been observed in a wild species. Koala retrovirus (KoRV) provides a unique opportunity to study this process of endogenisation in action as it still appears to be spreading through the koala population. Ongoing expression of the endogenous sequence and consequent high levels of viraemia have been linked to neoplasia and immunosuppression in koalas. This apparently recent invader of the koala genome shares a remarkably close sequence relationship with the pathogenic exogenous Gibbon ape leukaemia virus (GALV), and comparative analyses of KoRV and GALVare helping to shed light on how retroviruses in general adapt to a relatively benign or at least less pathogenic existence within a new host genome. (Part of a multi-author review).

  2. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells.

    Science.gov (United States)

    Liu, Xia; Zhao, Libo; Yang, Yongtao; Bode, Liv; Huang, Hua; Liu, Chengyu; Huang, Rongzhong; Zhang, Liang; Wang, Xiao; Zhang, Lujun; Liu, Siwen; Zhou, Jingjing; Li, Xin; He, Tieming; Cheng, Zhongyi; Xie, Peng

    2014-09-01

    Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. EBV Infection of Mice with Reconstituted Human Immune System Components.

    Science.gov (United States)

    Münz, Christian

    2015-01-01

    Epstein-Barr virus (EBV) was discovered 50 years ago as the first candidate human tumor virus. Since then, we have realized that this human γ-herpesvirus establishes persistent infection in the majority of adult humans, but fortunately causes EBV-associated diseases only in few individuals. This is an incredible success story of the human immune system, which controls EBV infection and its transforming capacity for decades. A better understanding of this immune control would not only benefit patients with EBV-associated malignancies, but could also provide clues how to establish such a potent, mostly cell-mediated immune control against other pathogens and tumors. However, the functional relevance of EBV-specific immune responses can only be addressed in vivo, and mice with reconstituted human immune system components (huMice) constitute a small animal model to interrogate the protective value of immune compartments during EBV infection, but also might provide a platform to test EBV-specific vaccines. This chapter will summarize the insights into EBV immunobiology that have already been gained in these models and provide an outlook into promising future avenues to develop this in vivo model of EBV infection and human immune responses further.

  4. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xia [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Fifth People' s Hospital of Shanghai, School of Medicine, Fudan University, Shanghai, 200240 (China); Zhao, Libo [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Third People' s Hospital of Chongqing, 400014 (China); Yang, Yongtao [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Bode, Liv [Bornavirus Research Group affiliated to the Free University of Berlin, Berlin (Germany); Huang, Hua [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Liu, Chengyu [Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Huang, Rongzhong [Department of Rehabilitative Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010 (China); Zhang, Liang [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); and others

    2014-09-15

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs.

  5. General Overview on Nontuberculous Mycobacteria, Biofilms, and Human Infection

    Directory of Open Access Journals (Sweden)

    Sonia Faria

    2015-01-01

    Full Text Available Nontuberculous mycobacteria (NTM are emergent pathogens whose importance in human health has been growing. After being regarded mainly as etiological agents of opportunist infections in HIV patients, they have also been recognized as etiological agents of several infections on immune-competent individuals and healthcare-associated infections. The environmental nature of NTM and their ability to assemble biofilms on different surfaces play a key role in their pathogenesis. Here, we review the clinical manifestations attributed to NTM giving particular importance to the role played by biofilm assembly.

  6. Computational and Statistical Analyses of Insertional Polymorphic Endogenous Retroviruses in a Non-Model Organism

    Directory of Open Access Journals (Sweden)

    Le Bao

    2014-11-01

    Full Text Available Endogenous retroviruses (ERVs are a class of transposable elements found in all vertebrate genomes that contribute substantially to genomic functional and structural diversity. A host species acquires an ERV when an exogenous retrovirus infects a germ cell of an individual and becomes part of the genome inherited by viable progeny. ERVs that colonized ancestral lineages are fixed in contemporary species. However, in some extant species, ERV colonization is ongoing, which results in variation in ERV frequency in the population. To study the consequences of ERV colonization of a host genome, methods are needed to assign each ERV to a location in a species’ genome and determine which individuals have acquired each ERV by descent. Because well annotated reference genomes are not widely available for all species, de novo clustering approaches provide an alternative to reference mapping that are insensitive to differences between query and reference and that are amenable to mobile element studies in both model and non-model organisms. However, there is substantial uncertainty in both identifying ERV genomic position and assigning each unique ERV integration site to individuals in a population. We present an analysis suitable for detecting ERV integration sites in species without the need for a reference genome. Our approach is based on improved de novo clustering methods and statistical models that take the uncertainty of assignment into account and yield a probability matrix of shared ERV integration sites among individuals. We demonstrate that polymorphic integrations of a recently identified endogenous retrovirus in deer reflect contemporary relationships among individuals and populations.

  7. [Establishment of the retrovirus-mediated murine model with MLL-AF9 leukemia].

    Science.gov (United States)

    Xu, Si-Miao; Yang, Yang; Zhou, Mi; Zhao, Xue-Jiao; Qin, Yu; Zhang, Pei-Ling; Yuan, Rui-Feng; Zhou, Jian-Feng; Fang, Yong

    2013-10-01

    This study was purposed to establish a retrovirus-mediated murine model with MLL-AF9 leukemia, so as to provide a basis for further investigation of the pathogenesis and therapeutic strategy of MLL associated leukemia. Murine (CD45.2) primary hematopoietic precursor positively selected for expression of the progenitor marker c-Kit by means of MACS were transduced with a retrovirus carrying MLL-AF9 fusion gene. After cultured in vitro, the transduced cells were injected intravenously through the tail vein into the lethally irradiated mice (CD45.1). PCR, flow cytometry and morphological observation were employed to evaluate the murine leukemia model system. The results showed that MLL-AF9 fusion gene was expressed in the infected cells, and the cells had a dramatically enhanced potential to generate myeloid colonies with primitive and immature morphology. Flow cytometric analysis revealed that the immortalized cells highly expressed myeloid lineage surface markers Gr-1 and Mac-1. Moreover, the expression levels of Hoxa9 and Meis1 mRNA were significantly higher in the MLL-AF9 cells than that in control. The mice transplanted with MLL-AF9 cells displayed typical signs of leukemia within 6-12 weeks. Extensive infiltration leukemic cells was observed in the Wright-Giemsa stained peripheral blood smear and bone marrow, and also in the histology of liver and spleen. Flow cytometric analysis of the bone marrow and spleen cells demonstrated that the CD45.2 populations expressed highly myeloid markers Gr-1 and Mac-1. The leukemic mice died within 12 weeks. It is concluded that the retrovirus-mediated murine model with MLL-AF9 leukemia is successfully established, which can be applied in the subsequent researches.

  8. Human Metapneumovirus Infection and Acute Respiratory Distress Syndrome During Pregnancy.

    Science.gov (United States)

    Fuchs, Alina; McLaren, Rodney; Saunders, Paul; Karakash, Scarlett; Minkoff, Howard

    2017-09-01

    Human metapneumovirus has recently been recognized as an important cause of severe respiratory viral infections and of viral infections in patients admitted to intensive care units. Little is known about the course of this infection in pregnancy. A late-preterm primigravid woman was admitted to the intensive care unit for acute respiratory distress syndrome and subsequently diagnosed with human metapneumovirus. Because of worsening maternal respiratory status, she was intubated and a primary cesarean delivery was performed. The patient's respiratory status continued to decline postpartum, and she ultimately required extracorporeal membrane oxygenation. She was treated supportively until her respiratory status improved, at which time she was extubated and weaned off extracorporeal membrane oxygenation and subsequently discharged home. Human metapneumovirus can lead to severe respiratory illness during pregnancy.

  9. Humanized mouse models for HIV-1 infection of the CNS.

    Science.gov (United States)

    Honeycutt, Jenna B; Sheridan, Patricia A; Matsushima, Glenn K; Garcia, J Victor

    2015-06-01

    Since the onset of the HIV epidemic, there has been a shift from a deadly diagnosis to the management of a chronic disease. This shift is the result of the development of highly effective drugs that are able to suppress viral replication for years. The availability of these regimens has also shifted the neurocognitive pathology associated with infection from potentially devastating to a much milder phenotype. As the disease outcome has changed significantly with the availability of antiretroviral therapy, there is an opportunity to re-evaluate the currently available models to address the neurocognitive pathology seen in suppressed patients. In the following, we seek to summarize the current literature on humanized mouse models and their utility in understanding how HIV infection leads to changes in the central nervous system (CNS). Also, we identify some of the unanswered questions regarding HIV infection of the CNS as well as the opportunities and limitations of currently existing models to address those questions. Finally, our conclusions indicate that the earlier humanized models used to study HIV infection in the CNS provided an excellent foundation for the type of work currently being performed using novel humanized mouse models. We also indicate the potential of some humanized mouse models that have not been used as of this time for the analysis of HIV infection in the brain.

  10. Multiple UBXN family members inhibit retrovirus and lentivirus production and canonical NFκΒ signaling by stabilizing IκBα.

    Science.gov (United States)

    Hu, Yani; O'Boyle, Kaitlin; Auer, Jim; Raju, Sagar; You, Fuping; Wang, Penghua; Fikrig, Erol; Sutton, Richard E

    2017-02-01

    UBXN proteins likely participate in the global regulation of protein turnover, and we have shown that UBXN1 interferes with RIG-I-like receptor (RLR) signaling by interacting with MAVS and impeding its downstream effector functions. Here we demonstrate that over-expression of multiple UBXN family members decreased lentivirus and retrovirus production by several orders-of-magnitude in single cycle assays, at the level of long terminal repeat-driven transcription, and three family members, UBXN1, N9, and N11 blocked the canonical NFκB pathway by binding to Cullin1 (Cul1), inhibiting IκBα degradation. Multiple regions of UBXN1, including its UBA domain, were critical for its activity. Elimination of UBXN1 resulted in early murine embryonic lethality. shRNA-mediated knockdown of UBXN1 enhanced human immunodeficiency virus type 1 (HIV) production up to 10-fold in single cycle assays. In primary human fibroblasts, knockdown of UBXN1 caused prolonged degradation of IκBα and enhanced NFκB signaling, which was also observed after CRISPR-mediated knockout of UBXN1 in mouse embryo fibroblasts. Knockout of UBXN1 significantly up- and down-regulated hundreds of genes, notably those of several cell adhesion and immune signaling pathways. Reduction in UBXN1 gene expression in Jurkat T cells latently infected with HIV resulted in enhanced HIV gene expression, consistent with the role of UBXN1 in modulating the NFκB pathway. Based upon co-immunoprecipitation studies with host factors known to bind Cul1, models are presented as to how UBXN1 could be inhibiting Cul1 activity. The ability of UBXN1 and other family members to negatively regulate the NFκB pathway may be important for dampening the host immune response in disease processes and also re-activating quiescent HIV from latent viral reservoirs in chronically infected individuals.

  11. Sequence of retrovirus provirus resembles that of bacterial transposable elements

    Science.gov (United States)

    Shimotohno, Kunitada; Mizutani, Satoshi; Temin, Howard M.

    1980-06-01

    The nucleotide sequences of the terminal regions of an infectious integrated retrovirus cloned in the modified λ phage cloning vector Charon 4A have been elucidated. There is a 569-base pair direct repeat at both ends of the viral DNA. The cell-virus junctions at each end consist of a 5-base pair direct repeat of cell DNA next to a 3-base pair inverted repeat of viral DNA. This structure resembles that of a transposable element and is consistent with the protovirus hypothesis that retroviruses evolved from the cell genome.

  12. Malignant syphilis with human immunodeficiency virus infection

    Directory of Open Access Journals (Sweden)

    Jiby Rajan

    2011-01-01

    Full Text Available Malignant syphilis or Lues maligna, commonly reported in the pre-antibiotic era, has now seen a resurgence with the advent of human immunodeficiency virus (HIV. Immunosuppression and sexual promiscuity set the stage for this deadly association of HIV and Treponema pallidum that can manifest atypically and can prove to cause diagnostic problems. We report one such case in a 30-year-old female who responded favorably to treatment with penicillin.

  13. Generation and maintenance of human memory cells during viral infection.

    Science.gov (United States)

    Halwani, Rabih; Doroudchi, Mehrnoosh; Yassine-Diab, Bader; Janbazian, Loury; Shi, Yu; Said, Elias A; Haddad, Elias K; Sékaly, Rafick-Pierre

    2006-11-01

    Long-term maintenance of memory T cell response is the hallmark of immune protection and hence the holy grail of most vaccine development studies. Persistent memory cells, developed after either viral infection or vaccination, ensure the generation of an antiviral response upon reexposure to the pathogen. During acute viral infections, as in the case of measles and influenza viruses, strong T cell effector functions, which eradicate the virus and protect patients against reexposure, are achieved by the generation of persistent protective memory cells. However, in chronic infections, T cells drastically lose effector functions before acquiring a memory phenotype. Chronic infections can be categorized into infections where viremia is controlled and protective memory cells are maintained as in the case of EBV and CMV infections, or where the virus persists and memory cells are exhausted and disrupted as in the case of human immunodeficiency virus infection. In this review, we will discuss the different phenotypical and functional characteristics of memory cells subsets, the importance of the role they play during acute and chronic infections, and the mechanisms behind their effectiveness and persistence.

  14. Obesity and human papillomavirus infection in perimenopausal women.

    Science.gov (United States)

    Liu, Su-Hsun; Rositch, Anne F; Viscidi, Raphael P; Silver, Michelle I; Burke, Anne E; Gravitt, Patti E

    2013-10-01

    Obesity is known to increase susceptibility to certain infections in men. It is unclear whether obesity increases women's risk for human papillomavirus (HPV) infection. In a prospective cohort of 696 perimenopausal women enrolled in 2008-2012, we sought to determine whether obesity predicted incident HPV detection or nondetection. Obesity was defined as body mass index (BMI) ≥ 30 kg/m(2). Baseline any type HPV prevalence was comparable between obese and nonobese women (18.7% vs 19.1%; P > .05). Over a median follow-up period of 17.9 months (interquartile range: 12.1-24.5), 187 new HPV detections occurred among 123 women, 60 of whom subsequently lost 76 detectable infections. When compared with nonobese participants, obese women had a similar rate of new HPV detection (7.1 vs 7.8 infections per 1000 infection-years; P > .05) or loss of detection (100.3 vs 85.8 infections per 100 infection-years; P > .05). Similar results were found after adjusting for age, menopausal status, smoking habit, and sexual exposure history. Results from the current analysis suggest little effect of obesity on HPV detection and loss of detection in mid-adult women. More research is needed to determine whether adipokines or cytokines better capture the potential immune modulating effects of obesity on HPV infection.

  15. Cytomegalovirus infection of the human placenta: an immunocytochemical study.

    Science.gov (United States)

    Mühlemann, K; Miller, R K; Metlay, L; Menegus, M A

    1992-11-01

    In congenital cytomegalovirus (CMV) infection histologic evaluation of the placenta is often unrevealing. In the present study immunocytochemistry to CMV immediate early and early nuclear antigens was used to characterize placental involvement in six cases of symptomatic intrauterine CMV infection. Histologic examination had demonstrated diagnostic viral inclusions in one placenta and non-specific villitis in another. However, immunocytochemistry revealed CMV infection in five of the six placentas, including three with no pathologic changes on routine histologic evaluation. Infected cells were located primarily in the villous stroma. In one case immunoperoxidase staining showed infection in the syncytiotrophoblast. Infected endothelial cells were demonstrated by double staining for CMV and factor VIII antigen. No double-stained cells were seen in tissue sections stained for CMV immediate early nuclear antigen or the human macrophage-associated CD68 antigen, which is expressed in Hofbauer cells. In conclusion, specific immunoperoxidase staining was more sensitive for demonstrating placental CMV infection than was histologic examination and it aided in the characterization of infected cells.

  16. Human bocavirus in children with acute respiratory infections in Vietnam.

    Science.gov (United States)

    Tran, Dinh Nguyen; Nguyen, Tran Quynh Nhu; Nguyen, Tuan Anh; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2014-06-01

    Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12-24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December-April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. © 2013 Wiley Periodicals, Inc.

  17. Animal-associated opportunistic infections among persons infected with the human immunodeficiency virus.

    Science.gov (United States)

    Glaser, C A; Angulo, F J; Rooney, J A

    1994-01-01

    A number of animal-associated infections occur in persons infected with the human immunodeficiency virus (HIV), including those due to Toxoplasma gondii, Cryptosporidium, Microsporida, Salmonella, Campylo-bacter, Giardia, Rhodococcus equi, Rochalimaea, and Listeria monocytogenes. Most of these infections, with the exception of those due to Rochalimaea, appear to be acquired by the immunosuppressed individual from sources other than exposure to animals. Drs. Glaser and colleagues review our current understanding of the role of exposure to animals, especially pets, in the natural history of these opportunistic infections. They suggest that the risk of zoonotic transmission is small and offer practical suggestions designed to reduce this low risk. They conclude that the benefits of animal companionship outweigh the risks to patients and that prohibition of pet ownership by individuals infected with HIV is not warranted.

  18. Borna Disease Virus Infection, a Human Mental-Health Risk

    Science.gov (United States)

    Bode, Liv; Ludwig, Hans

    2003-01-01

    This article focuses on human Borna disease virus (BDV) infections, most notably on the development of valid diagnostic systems, which have arisen as a major research issue in the past decade. The significance of a novel modular triple enzyme-linked immunosorbent assay that is capable of specifically measuring anti-BDV antibodies as well as major structural proteins N (p40) and P (p24) in the blood, either as free antigens in the plasma or as antibody-bound circulating immune complexes (CICs), is explained. The impact of CICs and plasma antigen, which indicate periods of antigenemia in the course of BDV infection, along with other infection markers that are still in use is discussed. The review further provides new insight into possible links of BDV to human diseases, summarizing cross-sectional and longitudinal data which correlate acute depression with the presence and amount of antigen and CICs. Moreover, BDV prevalence in healthy people is reevaluated, suggesting that this was previously underestimated. Antiviral efficacy of amantadine, in vivo and in vitro, is outlined as well, with emphasis on wild-type (human and equine) versus laboratory strains. Finally, the pros and cons of the association of BDV with human disease, as detailed in the literature, are critically discussed and related to our data and concepts. This article supports existing correlative evidence for a pathogenic role of BDV infection in particular human mental disorders, in analogy to what has been proven for a variety of animal species. PMID:12857781

  19. Characterizing novel endogenous retroviruses from genetic variation inferred from short sequence reads

    DEFF Research Database (Denmark)

    Mourier, Tobias; Mollerup, Sarah; Vinner, Lasse

    2015-01-01

    From Illumina sequencing of DNA from brain and liver tissue from the lion, Panthera leo, and tumor samples from the pike-perch, Sander lucioperca, we obtained two assembled sequence contigs with similarity to known retroviruses. Phylogenetic analyses suggest that the pike-perch retrovirus belongs...... to the epsilonretroviruses, and the lion retrovirus to the gammaretroviruses. To determine if these novel retroviral sequences originate from an endogenous retrovirus or from a recently integrated exogenous retrovirus, we assessed the genetic diversity of the parental sequences from which the short Illumina reads...

  20. Zika Virus Infects Human Fetal Brain Microglia and Induces Inflammation.

    Science.gov (United States)

    Lum, Fok-Moon; Low, Donovan K S; Fan, Yiping; Tan, Jeslin J L; Lee, Bernett; Chan, Jerry K Y; Rénia, Laurent; Ginhoux, Florent; Ng, Lisa F P

    2017-04-01

    The unprecedented reemergence of Zika virus (ZIKV) has startled the world with reports of increased microcephaly in Brazil. ZIKV can infect human neural progenitors and impair brain growth. However, direct evidence of ZIKV infection in human fetal brain tissues remains elusive. Investigations were performed with brain cell preparations obtained from 9 donors. Virus infectivity was assessed by detection of virus antigen by flow cytometry together with various hematopoietic cell surface markers. Virus replication was determined by viral RNA quantification. Cytokine levels in supernatant obtained from virus-infected fetal brain cells were measured simultaneously in microbead-based immunoassays. We also show that ZIKV infection was particularly evident in hematopoietic cells with microglia, the brain-resident macrophage population being one of the main targets. Infection induces high levels of proinflammatory immune mediators such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and monocyte chemotactic protein 1 (MCP-1). Our results highlight an important role for microglia and neuroinflammation during congenital ZIKV pathogenesis.

  1. Microsphaeropsis olivacea as an etiological agent of human skin infection.

    Science.gov (United States)

    Guarro, J; Mayayo, E; Tapiol, J; Aguilar, C; Cano, J

    1999-04-01

    Microsphaeropsis olivacea is reported as the agent of a case of human skin infection in an otherwise healthy woman. This fungus has not been reported previously as causing disease in humans. It was identified on the basis of its production of pycnidia and conidial structures typical of the Coelomycetes, and by its light brown, ellipsoid to cylindrical and thick walled conidia. The in vitro inhibitory activity of amphotericin B, fluconazole, flucytosine, itraconazole, ketoconazole and miconazole was determined.

  2. Human dendritic cell culture and bacterial infection.

    Science.gov (United States)

    Jones, Hannah E; Klein, Nigel; Dixon, Garth L J

    2012-01-01

    Dendritic cells (DC) play a key role in the development of natural immunity to microbes. The DC form a bridge between the innate and adaptive immune system by providing key instructions particularly to antigen naïve T-cells. The interaction of DC with T lymphocytes involves three signals: (1) antigen processing and presentation in context of MHC Class I and/or II, (2) expression of T cell co-stimulatory molecules, and (3) cytokine production. Studying the interactions of DCs with specific pathogens allows for better understanding of how protective immunity is generated, and may be particularly useful for assessing vaccine components. In this chapter, we describe methods to generate human monocyte-derived DCs and assess their maturation, activation, and function, using interaction with the gram-negative bacterial pathogen Neisseria meningitidis as a model.

  3. Severe human Babesia divergens infection in Norway

    Directory of Open Access Journals (Sweden)

    K. Mørch

    2015-04-01

    Full Text Available Human babesiosis is a rare but potentially life-threatening parasitic disease transmitted by ixodid ticks, and has not previously been reported in Norway. We report a case of severe babesiosis that occurred in Norway in 2007. The patient had previously undergone a splenectomy. He was frequently exposed to tick bites in an area endemic for bovine babesiosis in the west of Norway. The patient presented with severe haemolysis and multiorgan failure. Giemsa-stained blood smears revealed 30% parasitaemia with Babesia spp. He was treated with quinine in combination with clindamycin, apheresis, and supportive treatment with ventilatory support and haemofiltration, and made a complete recovery. This is the first case reported in Norway; however Babesia divergens seroprevalence in cattle in Norway is high, as is the risk of Ixodes ricinus tick bite in the general population. Babesiosis should be considered in the differential diagnosis of unexplained febrile haemolytic disease.

  4. Mapping of a neutralizing epitope in the surface envelope protein of porcine endogenous retrovirus subgroup B.

    Science.gov (United States)

    Nakaya, Yuki; Hoshino, Shigeki; Yasuda, Jiro; Miyazawa, Takayuki

    2011-04-01

    Pigs are thought to be the most suitable donor animal for xenotransplantation. However, pigs harbour potentially hazardous infectious agents, termed porcine endogenous retroviruses (PERVs), in their genome. In this study, we generated a mAb against PERV-B surface (SU) envelope protein (Env), designated KRT1. KRT1 binding was detected by an indirect immunofluorescence assay and flow cytometric analysis on cells infected with PERV-B. KRT1 neutralized PERV-B pseudotype virus and specifically recognized PERV-B SU Env, but not PERV-A SU Env by immunoblotting analysis. The peptide-ELISA revealed that KRT1 recognized a linear peptide sequence (ALEPPHNLPVP) residing in a proline-rich region that is one of the subdomains of SU Env. In conclusion, the KRT1 antibody will serve as a useful tool for the study of PERV-B and, more importantly, it may provide new protective strategies against PERV-B infection in xenotransplantation.

  5. Controlled Human Malaria Infection: Applications, Advances, and Challenges.

    Science.gov (United States)

    Stanisic, Danielle I; McCarthy, James S; Good, Michael F

    2018-01-01

    Controlled human malaria infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or by direct injection of sporozoites or parasitized erythrocytes. When required, the resulting blood-stage infection is curtailed by the administration of antimalarial drugs. Inducing a malaria infection via inoculation with infected blood was first used as a treatment (malariotherapy) for neurosyphilis in Europe and the United States in the early 1900s. More recently, CHMI has been applied to the fields of malaria vaccine and drug development, where it is used to evaluate products in well-controlled early-phase proof-of-concept clinical studies, thus facilitating progression of only the most promising candidates for further evaluation in areas where malaria is endemic. Controlled infections have also been used to immunize against malaria infection. Historically, CHMI studies have been restricted by the need for access to insectaries housing infected mosquitoes or suitable malaria-infected individuals. Evaluation of vaccine and drug candidates has been constrained in these studies by the availability of a limited number of Plasmodium falciparum isolates. Recent advances have included cryopreservation of sporozoites, the manufacture of well-characterized and genetically distinct cultured malaria cell banks for blood-stage infection, and the availability of Plasmodium vivax -specific reagents. These advances will help to accelerate malaria vaccine and drug development by making the reagents for CHMI more widely accessible and also enabling a more rigorous evaluation with multiple parasite strains and species. Here we discuss the different applications of CHMI, recent advances in the use of CHMI, and ongoing challenges for consideration. Copyright © 2017 American Society for Microbiology.

  6. The effect of human papillomavirus infection on sperm cell motility.

    Science.gov (United States)

    Lai, Y M; Lee, J F; Huang, H Y; Soong, Y K; Yang, F P; Pao, C C

    1997-06-01

    To investigate the presence of human papillomavirus (HPV) in human sperm cells and to evaluate potential effects of HPV on the sperm functions. A descriptive clinical study. Specimens of semen were collected from 24 randomly selected patients who attended the fertility clinics at Chang Gung Memorial Hospital. The presence of HPV DNA and RNA were examined by polymerase chain reaction. Semen quality and sperm cell function were analyzed by computer-aided autoanalyzer. Human papillomavirus type 16 DNA and RNA were found in 6 (25%) and 2 (8%) of the sperm cells specimens, respectively. Human papillomavirus type 18 DNA and RNA were present in 11 (46%) and 5 (21%) of the same sperm cells specimens, respectively. Incidence of asthenozoospermia among patients infected with either HPV was significantly higher than in those without HPV in their sperm cells (75% versus 8%). Although performance of curvilinear velocity, straight-line velocity, and mean amplitude of lateral head displacement was significantly lower in HPV-infected specimens, the differences of linearity, beat cross frequency, and straightness were not statistically significant. These results suggest that human papillomavirus can be found in human sperm cells and that certain HPV-specific genes are actively transcribed. Sperm motility parameters seem to be affected by the presence of HPV in the sperm cells, and also the incidence of asthenozoospermia may be associated with HPV infection.

  7. Local Risk Factors in Genital Human Papilloma Virus Infection in ...

    African Journals Online (AJOL)

    Papdopoulus AG, Devaja O, Cason J, Raju KS. The clinical implications of human papilloma virus infection in cervical cancinogenesis and emerging therapies. In: Studd J, editor. Prorgess in Obstetrics and Gynaecology. Vol. 14. Edinburgh: Churchhill Livingstone Publications; 2000. p. 281‑93. 2. Ijaiya MA, Aboyeji PA, ...

  8. Declining Rate of Infection with Maternal Human Immunodeficiency ...

    African Journals Online (AJOL)

    Declining Rate of Infection with Maternal Human Immunodeficiency Virus at Delivery Units in North-Central Nigeria. GE Imade, AS Sagay, J Musa, AN Ocheke, DS Adeniyi, M Idighri, R Powl, A Sendeht, JP Ogwuche, M Elujoba, CO Egbodo, T Oyebode, PH Daru, O Agbaji, IC Pam, ST Meloni, P Okonkwo, PJ Kanki ...

  9. Age-specific prevalence of cervical human papillomavirus infection ...

    African Journals Online (AJOL)

    This cross-sectional study describes the age-specific prevalence of human papillomavirus (HPV) infection and cytological abnormalities among this urban and peri-urban population. Method. Over the period March 2009 - September 2011, 1 524 women attending public sector primary healthcare clinics were invited to

  10. Local Risk Factors in Genital Human Papilloma Virus Infection in ...

    African Journals Online (AJOL)

    cervical cancer and identified other risk factors. Molecular epidemiologic evidence clearly indicates that certain types of. HPV are the principal cause of invasive cancer and cervical intraepithelial neoplasia.[3]. Local Risk Factors in Genital Human Papilloma Virus. Infection in Cervical Smears. Ojiyi EC, Dike IE, Okeudo C, ...

  11. Autochthonous Nocardia cerradoensis Infection in Humans, Spain, 2011 and 2014

    Science.gov (United States)

    Ercibengoa, Maria; Pérez-Trallero, Emilio

    2016-01-01

    Nocardia cerradoensis was first isolated in 2003 in the El Cerrado region of Brazil; since then, only 2 human infections, in France and Spain, have been reported. We describe 3 autochthonous cases in residents of Spain during 2011 and 2014. Together these cases support the idea of an emerging global pathogenic microorganism. PMID:26691545

  12. Prevalence of human immunodeficiency virus (HIV) infection among ...

    African Journals Online (AJOL)

    Prevalence of human immunodeficiency virus (HIV) infection among pregnant women in an antenatal clinic in Port-Harcourt, Nigeria. ... 6, No 3 (2007) >. Log in or Register to get access to full text downloads. ... A total of 10,032 pregnant women were screened for the possible occurrence of HIV 1 and HIV 2 within the period.

  13. Awareness of Human Immunodeficiency Virus (HIV) infection among ...

    African Journals Online (AJOL)

    Objective: To determine the level of awareness of Human Immunodeficiency Virus (HIV) infection among antenatal clients in Nnewi Nigeria. Subjects and Methods: A cross sectional descriptive study of six hundred consecutive antenatal clients attending the Nnamdi Azikiwe University Teaching Hospital and five private ...

  14. Prevalence of human immunodeficiency virus infection among ...

    African Journals Online (AJOL)

    Prevalence of human immunodeficiency virus infection among tuberculosis suspect patients in Accra, Ghana, ... man immunodeficiency virus (HIV) and tuberculosis. (TB) is well known. A previous study showed a 16,8 % .... HIV~1 and HIV-(Z; Fujirebio Inc, TokyoJapan) and con-- firmed with the synthetic peptide based ...

  15. seroprevalence of human herpes virus 8 (hhv8) infection among ...

    African Journals Online (AJOL)

    Praise

    SEROPREVALENCE OF HUMAN HERPES VIRUS 8 (HHV8) INFECTION. AMONG COMMERCIAL SEX WORKERS IN JOS. Zakari1, H., Nimzing2, L., Agabi1, Y. A., Amagam3, P. and Dashen,1 M. M.. 1Department of Microbiology, Faculty of Natural Sciences, University o f Jos, Nigeria. 2Department of Medical Microbiology, ...

  16. Prevalence And Risk Factors For Human Pappiloma Virus Infection ...

    African Journals Online (AJOL)

    Human Pappiloma Virus (HPV) infection is a disease of global public health importance, culminating into a high risk of cervical cancer. Most of the risk factors are modifiable, thus making HPV itself preventable. Efforts towards community HPV prevention and vaccination have not yielded the desired results, most especially ...

  17. Health Disparity in Human Papilloma Virus Related Infections | Poku ...

    African Journals Online (AJOL)

    In spite of the volume of information of Human Papilloma Virus (HPV) and the HPV vaccines, there are racial and gender differences in the knowledge and awareness of HPV among Guyanese. The study aimed to assess the knowledge and attitude towards HPV infection, cervical cancer and HPV vaccines. The study was ...

  18. Prevalence of tonsillar human papillomavirus infections in Denmark

    DEFF Research Database (Denmark)

    Rusan, M; Klug, Tejs Ehlers; Henriksen, Jens-Jacob Mølby

    2014-01-01

    The incidence of tonsillar carcinomas associated with Human Papillomavirus (HPV) infection has increased dramatically over the last three decades. In fact, currently in Scandinavia, HPV-associated cases account for over 80 % of tonsillar carcinoma cases. Yet, the epidemiology and natural history...

  19. Human Papillomavirus Infection Among 2460 Men in Denmark

    DEFF Research Database (Denmark)

    Hebnes, Julie Buchholt; Munk, Christian; Nøhr, Bugge

    2015-01-01

    BACKGROUND: It is crucial to understand the epidemiology and natural history of human papillomavirus (HPV) infection in both men and women, to prevent the increasing HPV-related disease burden in men. Data on HPV prevalence among men in the general population are limited. In this cross...

  20. Nocardia brasiliensis: from microbe to human and experimental infections.

    Science.gov (United States)

    Salinas-Carmona, M C

    2000-09-01

    Nocardia brasiliensis is a Gram-positive bacterium that lives as a saprophyte in soil. In this article the physical properties, chemical composition and taxonomic position of this species is reviewed. Human infections and an experimental model of actinomycetoma in BALB/c mice as well as the host-immune response is described.

  1. Prevalence of Human Rhinovirus Infection in Children with Acute ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    Prevalence of Human Rhinovirus Infection in Children with. Acute Respiratory Symptoms in Ilorin, Nigeria. Olatunji Matthew Kolawole\\ Busayo Joseph Adeyemf1 and Aishat Abdulrahman. Gobir2. 1lnfectious Diseases and Environmental Health Research Group, Department of Microbiology,. Faculty of Life Sciences ...

  2. Campylobacter: animal reservoirs, human infections, and options for control

    NARCIS (Netherlands)

    Wagenaar, Jaap; Newell, D.G.; Kalupahana, R.S.; Mughini Gras, Lapo

    2015-01-01

    Campylobacteriosis is a frequently diagnosed disease in humans. Most infections are considered food-borne and are caused by Campylobacter jejuni and C. coli. The animal reservoirs of these Campylobacter, and the sources and routes of transmission, are described and discussed. Most warm-blooded

  3. Human skin Langerhans cells are targets of dengue virus infection

    NARCIS (Netherlands)

    Wu, SJL; Grouard-Vogel, G; Mascola, [No Value; Brachtel, E; Putvatana, R; Louder, MK; Filgueira, L; Marovich, MA; Wong, HK; Blauvelt, A; Murphy, GS; Robb, ML; Innes, BL; Birx, DL; Hayes, CG; Frankel, SS

    Dengue virus (DV), an arthropod-borne flavivirus, causes a febrile illness for which there is no antiviral treatment and no vaccine(1,2). Macrophages are important in dengue pathogenesis; however, the initial target cell for DV infection remains unknown. As DV is introduced into human skin by

  4. Report of the first human case of Caulobacter sp. infection

    DEFF Research Database (Denmark)

    Justesen, Ulrik S; Holt, Hanne M; Thiesson, Helle

    2007-01-01

    A Caulobacter sp. isolate was recovered from the dialysis fluid of a patient undergoing peritoneal dialysis. Bacterial identification included electron microscopy and 16S rDNA sequencing. To our knowledge, this is the first report of human Caulobacter infection. Special growth requirements suggest...

  5. Human Papillomavirus Infection, Infertility, and Assisted Reproductive Outcomes

    Directory of Open Access Journals (Sweden)

    Nigel Pereira

    2015-01-01

    Full Text Available The human papillomavirus (HPV is a sexually transmitted infection common among men and women across all geographic and socioeconomic subgroups worldwide. Recent evidence suggests that HPV infection may affect fertility and alter the efficacy of assisted reproductive technologies. In men, HPV infection can affect sperm parameters, specifically motility. HPV-infected sperm can transmit viral DNA to oocytes, which may be expressed in the developing blastocyst. HPV can increase trophoblastic apoptosis and reduce the endometrial implantation of trophoblastic cells, thus increasing the theoretical risk of miscarriage. Vertical transmission of HPV during pregnancy may be involved in the pathophysiology of preterm rupture of membranes and spontaneous preterm birth. In patients undergoing intrauterine insemination for idiopathic infertility, HPV infection confers a lower pregnancy rate. In contrast, the evidence regarding any detrimental impact of HPV infection on IVF outcomes is inconclusive. It has been suggested that vaccination could potentially counter HPV-related sperm impairment, trophoblastic apoptosis, and spontaneous miscarriages; however, these conclusions are based on in vitro studies rather than large-scale epidemiological studies. Improvement in the understanding of HPV sperm infection mechanisms and HPV transmission into the oocyte and developing blastocyst may help explain idiopathic causes of infertility and miscarriage.

  6. Human Immunodeficiency Virus Infection and Host Defense in the Lungs.

    Science.gov (United States)

    Charles, Tysheena P; Shellito, Judd E

    2016-04-01

    Immunosuppression associated with human immunodeficiency virus (HIV) infection impacts all components of host defense against pulmonary infection. Cells within the lung have altered immune function and are important reservoirs for HIV infection. The host immune response to infected lung cells further compromises responses to a secondary pathogenic insult. In the upper respiratory tract, mucociliary function is impaired and there are decreased levels of salivary immunoglobulin A. Host defenses in the lower respiratory tract are controlled by alveolar macrophages, lymphocytes, and polymorphonuclear leukocytes. As HIV infection progresses, lung CD4 T cells are reduced in number causing a lack of activation signals from CD4 T cells and impaired defense by macrophages. CD8 T cells, on the other hand, are increased in number and cause lymphocytic alveolitis. Specific antibody responses by B-lymphocytes are decreased and opsonization of microorganisms is impaired. These observed defects in host defense of the respiratory tract explain the susceptibility of HIV-infected persons for oropharyngeal candidiasis, bacterial pneumonia, Pneumocystis pneumonia, and other opportunistic infections. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  7. Human Papillomavirus Infection, Infertility, and Assisted Reproductive Outcomes.

    Science.gov (United States)

    Pereira, Nigel; Kucharczyk, Katherine M; Estes, Jaclyn L; Gerber, Rachel S; Lekovich, Jovana P; Elias, Rony T; Spandorfer, Steven D

    2015-01-01

    The human papillomavirus (HPV) is a sexually transmitted infection common among men and women across all geographic and socioeconomic subgroups worldwide. Recent evidence suggests that HPV infection may affect fertility and alter the efficacy of assisted reproductive technologies. In men, HPV infection can affect sperm parameters, specifically motility. HPV-infected sperm can transmit viral DNA to oocytes, which may be expressed in the developing blastocyst. HPV can increase trophoblastic apoptosis and reduce the endometrial implantation of trophoblastic cells, thus increasing the theoretical risk of miscarriage. Vertical transmission of HPV during pregnancy may be involved in the pathophysiology of preterm rupture of membranes and spontaneous preterm birth. In patients undergoing intrauterine insemination for idiopathic infertility, HPV infection confers a lower pregnancy rate. In contrast, the evidence regarding any detrimental impact of HPV infection on IVF outcomes is inconclusive. It has been suggested that vaccination could potentially counter HPV-related sperm impairment, trophoblastic apoptosis, and spontaneous miscarriages; however, these conclusions are based on in vitro studies rather than large-scale epidemiological studies. Improvement in the understanding of HPV sperm infection mechanisms and HPV transmission into the oocyte and developing blastocyst may help explain idiopathic causes of infertility and miscarriage.

  8. Hybridization capture reveals evolution and conservation across the entire Koala retrovirus genome.

    Science.gov (United States)

    Tsangaras, Kyriakos; Siracusa, Matthew C; Nikolaidis, Nikolas; Ishida, Yasuko; Cui, Pin; Vielgrader, Hanna; Helgen, Kristofer M; Roca, Alfred L; Greenwood, Alex D

    2014-01-01

    The koala retrovirus (KoRV) is the only retrovirus known to be in the midst of invading the germ line of its host species. Hybridization capture and next generation sequencing were used on modern and museum DNA samples of koala (Phascolarctos cinereus) to examine ca. 130 years of evolution across the full KoRV genome. Overall, the entire proviral genome appeared to be conserved across time in sequence, protein structure and transcriptional binding sites. A total of 138 polymorphisms were detected, of which 72 were found in more than one individual. At every polymorphic site in the museum koalas, one of the character states matched that of modern KoRV. Among non-synonymous polymorphisms, radical substitutions involving large physiochemical differences between amino acids were elevated in env, potentially reflecting anti-viral immune pressure or avoidance of receptor interference. Polymorphisms were not detected within two functional regions believed to affect infectivity. Host sequences flanking proviral integration sites were also captured; with few proviral loci shared among koalas. Recently described variants of KoRV, designated KoRV-B and KoRV-J, were not detected in museum samples, suggesting that these variants may be of recent origin.

  9. Hybridization capture reveals evolution and conservation across the entire Koala retrovirus genome.

    Directory of Open Access Journals (Sweden)

    Kyriakos Tsangaras

    Full Text Available The koala retrovirus (KoRV is the only retrovirus known to be in the midst of invading the germ line of its host species. Hybridization capture and next generation sequencing were used on modern and museum DNA samples of koala (Phascolarctos cinereus to examine ca. 130 years of evolution across the full KoRV genome. Overall, the entire proviral genome appeared to be conserved across time in sequence, protein structure and transcriptional binding sites. A total of 138 polymorphisms were detected, of which 72 were found in more than one individual. At every polymorphic site in the museum koalas, one of the character states matched that of modern KoRV. Among non-synonymous polymorphisms, radical substitutions involving large physiochemical differences between amino acids were elevated in env, potentially reflecting anti-viral immune pressure or avoidance of receptor interference. Polymorphisms were not detected within two functional regions believed to affect infectivity. Host sequences flanking proviral integration sites were also captured; with few proviral loci shared among koalas. Recently described variants of KoRV, designated KoRV-B and KoRV-J, were not detected in museum samples, suggesting that these variants may be of recent origin.

  10. Human Papillomavirus Infections in Primary Care

    Science.gov (United States)

    Ogunmodede, Folashade; Yale, Steven H.; Krawisz, Bruce; Tyler, Gregory C.; Evans, Anthony C.

    2007-01-01

    Cervical cancer continues to be a leading cause of mortality worldwide. The incidence and mortality associated with invasive cervical cancer have declined significantly in developed countries due to widespread availability of screening with the Papanicolaou (Pap) test. However, the incidence and prevalence of non-invasive cervical intraepithelial neoplasms and genital warts related to oncogenic and nononcogenic strains of human papilloma viruses (HPV) have remained relatively stable. Recent advances in molecular diagnostics have resulted in improved characterization of various HPV types and have led to changes in terminology of Pap test findings. Changes in nomenclature may lead to confusion among primary care providers regarding how best to further evaluate abnormal cytological results. This article provides a concise overview of the approach to the treatment of genital warts and management of abnormal cervical cytology based on guidelines from the American Society of Colposcopy and Cervical Pathology. It also reviews advances in HPV vaccine development and the new recombinant vaccine recently approved for use in the United States. PMID:18086908

  11. Proliferation of endogenous retroviruses in the early stages of a host germ line invasion.

    Science.gov (United States)

    Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D; Roca, Alfred L

    2015-01-01

    Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire-dam-progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5'- and 3'-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5'-LTR sequence was identical to the 3'-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200-49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Phylogenetic evidence that two distinct Trichuris genotypes infect both humans and non-human primates.

    Directory of Open Access Journals (Sweden)

    Damiana F Ravasi

    Full Text Available Although there has been extensive debate about whether Trichuris suis and Trichuris trichiura are separate species, only one species of the whipworm T. trichiura has been considered to infect humans and non-human primates. In order to investigate potential cross infection of Trichuris sp. between baboons and humans in the Cape Peninsula, South Africa, we sequenced the ITS1-5.8S-ITS2 region of adult Trichuris sp. worms isolated from five baboons from three different troops, namely the Cape Peninsula troop, Groot Olifantsbos troop and Da Gama Park troop. This region was also sequenced from T. trichiura isolated from a human patient from central Africa (Cameroon for comparison. By combining this dataset with Genbank records for Trichuris isolated from other humans, non-human primates and pigs from several different countries in Europe, Asia, and Africa, we confirmed the identification of two distinct Trichuris genotypes that infect primates. Trichuris sp. isolated from the Peninsula baboons fell into two distinct clades that were found to also infect human patients from Cameroon, Uganda and Jamaica (named the CP-GOB clade and China, Thailand, the Czech Republic, and Uganda (named the DG clade, respectively. The divergence of these Trichuris clades is ancient and precedes the diversification of T. suis which clustered closely to the CP-GOB clade. The identification of two distinct Trichuris genotypes infecting both humans and non-human primates is important for the ongoing treatment of Trichuris which is estimated to infect 600 million people worldwide. Currently baboons in the Cape Peninsula, which visit urban areas, provide a constant risk of infection to local communities. A reduction in spatial overlap between humans and baboons is thus an important measure to reduce both cross-transmission and zoonoses of helminthes in Southern Africa.

  13. Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

    Directory of Open Access Journals (Sweden)

    Leonardo D'Aiuto

    Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

  14. Mechanism of Human Papillomavirus Binding to Human Spermatozoa and Fertilizing Ability of Infected Spermatozoa

    OpenAIRE

    Carlo Foresta; Cristina Patassini; Alessandro Bertoldo; Massimo Menegazzo; Felice Francavilla; Luisa Barzon; Alberto Ferlin

    2011-01-01

    Human papillomaviruses (HPVs) are agents of the most common sexually transmitted diseases in females and males. Precise data about the presence, mechanism of infection and clinical significance of HPV in the male reproductive tract and especially in sperm are not available. Here we show that HPV can infect human sperm, it localizes at the equatorial region of sperm head through interaction between the HPV capsid protein L1 and syndecan-1. Sperm transfected with HPV E6/E7 genes and sperm expos...

  15. Human Dirofilaria repens Infection in Romania: A Case Report

    Directory of Open Access Journals (Sweden)

    Ioana Popescu

    2012-01-01

    Full Text Available Human dirofilariasis is a zoonotic infectious disease caused by the filarial nematodes of dogs Dirofilaria repens and Dirofilaria immitis. Depending on the species involved, human infections usually manifest as one cutaneous or visceral larva migrans that forms a painless nodule in the later course of disease. Dirofilariae are endemic in the Mediterranean, particularly in Italy. They are considered as emerging pathogens currently increasing their geographical range. We present one of the few known cases of human dirofilariasis caused by D. repens in Romania. The patient developed unusual and severe clinical manifestations that mimicked pathological conditions like cellulitis or deep venous thrombosis.

  16. Human Trichinella infection outbreaks in Slovakia, 1980-2008.

    Science.gov (United States)

    Dubinský, Pavol; Antolová, Daniela; Reiterová, Katarína

    2016-03-01

    Trichinellosis, a parasitic zoonosis with world-wide distribution, causes serious health problems in humans and is also of economic importance. In Slovakia the most frequent species is T. britovi, causing disease mainly in wild life species. T. spiralis occurs less frequently and T. pseudospiralis only sporadically. The paper describes the epidemiology of six human Trichinella infection outbreaks recorded in Slovakia between 1980 and 2008. Before 1990 wild boar meat was the main source of infection. Later, risk farm practices, especially feeding of pigs with the wild animal´s offal contributed to the formation of synanthropic cycle and pig meat caused the epidemics in 1990, 2001 and 2008. Sausages prepared from pork and T. britovi infected dog meat and offered as a local food specialty on traditional folk festival in 1998 (Brezno district, Central Slovakia) were the source of the largest human outbreak recorded in Slovakia. The anti-Trichinella antibodies were detected in 336 event visitors. The main reason of repeated human epidemics in Slovakia has been the permanent circulation of Trichinella spp. in sylvatic cycle, especially in red foxes and wild boars. High population density of both animal species, persistent prevalence of trichinellosis in wild boars and even increasing positivity of red foxes suggest that the risk of human outbreaks in Slovakia persists.

  17. Infection prevention and control during prolonged human space travel.

    Science.gov (United States)

    Mermel, Leonard A

    2013-01-01

    Prolonged human spaceflight to another planet or an asteroid will introduce unique challenges of mitigating the risk of infection. During space travel, exposure to microgravity, radiation, and stress alter human immunoregulatory responses, which can in turn impact an astronaut's ability to prevent acquisition of infectious agents or reactivation of latent infection. In addition, microgravity affects virulence, growth kinetics, and biofilm formation of potential microbial pathogens. These interactions occur in a confined space in microgravity, providing ample opportunity for heavy microbial contamination of the environment. In addition, there is the persistence of aerosolized, microbe-containing particles. Any mission involving prolonged human spaceflight must be carefully planned to minimize vulnerabilities and maximize the likelihood of success.

  18. Seroprevalence of retrovirus in North American captive macropodidae.

    Science.gov (United States)

    Georoff, Timothy A; Joyner, Priscilla H; Hoover, John P; Payton, Mark E; Pogranichniy, Roman M

    2008-09-01

    Laboratory records of serology results from captive macropodidae sampled between 1997 and 2005 were reviewed to assess the seroprevalence of retrovirus exposure. Serum samples from 269 individuals (136 males, 133 females) representing 10 species of macropods housed in 31 North American captive collections were analyzed for retrovirus antibody using an indirect immunofluorescent assay. The prevalence of positive antibody titers comparing male versus female, between species, between age groups, and among animals with identified parentage was examined by nonparametric statistical analyses. Median age of animals at time of sample collection was 36 mo (range 2-201 mo). Total percentage seropositive was 20.4%. Serum antibody was detected in 31 of 47 (66.0%) tammar wallaby (Macropus eugenii), nine of 24 (37.5%) yellow-footed rock wallaby (Petrogale xanthopus), four of 11 (36.4%) swamp wallaby (Wallabia bicolor), 10 of 80 (12.5%) red-necked wallaby (Macropus rufogriseus), and one of 54 (1.9%) parma wallaby (Macropus parma). No individuals of western gray kangaroo (n=3) (Macropus fuliginosus), eastern gray kangaroo (n=19) (Macropus giganteus), common wallaroo (n=6) (Macropus robustus), red kangaroo (n=11) (Macropus rufus), or Matschie's tree kangaroo (n=14) (Dendrolagus matschiei) were positive for retrovirus antibody. These results demonstrate that five species of captive macropods have a history of exposure to retrovirus, with the highest percentage seropositive and highest statistical correlation in M. eugenii (pair-wise Fisher's exact test, alpha = 0.05). Additionally, one wild-caught M. eugenii was confirmed seropositive during quarantine period, indicating that retrovirus exposure may exist in wild populations.

  19. Relationship between cytomegalovirus infection and procoagulant changes in human immunodeficiency virus-infected patients

    NARCIS (Netherlands)

    Mulder, R.; Tichelaar, Y. I. G. V.; Sprenger, H. G.; Mulder, A. B.; Lijfering, W. M.

    P>Cytomegalovirus is associated with hypercoagulability, and is reported to increase the risk of venous thrombosis in human immunodeficiency virus (HIV)-infected patients. Progression to AIDS, however, is also associated with hypercoagulability and venous thrombosis, and may result in more

  20. Hepatitis C virus infection in the human immunodeficiency virus infected patient

    DEFF Research Database (Denmark)

    Clausen, Louise Nygaard; Lundbo, Lene Fogt; Benfield, Thomas

    2014-01-01

    Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes; therefore, coinfection is frequent. An estimated 5-10 million individuals alone in the western world are infected with both viruses. The majority of people acquire HCV by injection drug use and...

  1. Prevalence of human papilloma virus infection in patients with male accessory gland infection.

    Science.gov (United States)

    La Vignera, S; Vicari, E; Condorelli, R A; Franchina, C; Scalia, G; Morgia, G; Perino, A; Schillaci, R; Calogero, A E

    2015-04-01

    The frequency of human papillomavirus (HPV) infection in the semen of patients with male accessory gland infection (MAGI) was evaluated. One hundred infertile patients with MAGI were classified into group A: patients with an inflammatory MAGI (n = 48) and group B: patients with a microbial form (n = 52). Healthy age-matched fertile men (34.0 ± 4.0 years) made up the control group (n = 20). Amplification of HPV DNA was carried out by HPV-HS Bio nested polymerase chain reaction for the detection of HPV DNA sequences within the L1 ORF. Ten patients in group A (20.8%) and 15 patients in group B (28.8%) had a HPV infection; two controls (10.0%) had HPV infection. Patients with MAGI had a significantly higher frequency of HPV infection compared with controls; patients with a microbial MAGI had significantly higher frequency of HPV infection compared with patients with an inflammatory form (both P HPV had a slight, but significantly lower sperm progressive motility and normal morphology compared with patients with MAGI HPV-negative (P HPV infection occurred in patients with MAGI, suggesting that HPV should be investigated in the diagnostic work-up of these patients. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  2. Human parasitic protozoan infection to infertility: a systematic review.

    Science.gov (United States)

    Shiadeh, Malihe Nourollahpour; Niyyati, Maryam; Fallahi, Shirzad; Rostami, Ali

    2016-02-01

    Protozoan parasitic diseases are endemic in many countries worldwide, especially in developing countries, where infertility is a major burden. It has been reported that such infections may cause infertility through impairment in male and female reproductive systems. We searched Medline, PubMed, and Scopus databases and Google scholar to identify the potentially relevant studies on protozoan parasitic infections and their implications in human and animal model infertility. Literature described that some of the protozoan parasites such as Trichomonas vaginalis may cause deformities of the genital tract, cervical neoplasia, and tubal and atypical pelvic inflammations in women and also non-gonoccocal urethritis, asthenozoospermia, and teratozoospermia in men. Toxopalasma gondii could cause endometritis, impaired folliculogenesis, ovarian and uterine atrophy, adrenal hypertrophy, vasculitis, and cessation of estrus cycling in female and also decrease in semen quality, concentration, and motility in male. Trypanosoma cruzi inhibits cell division in embryos and impairs normal implantation and development of placenta. Decrease in gestation rate, infection of hormone-producing glands, parasite invasion of the placenta, and overproduction of inflammatory cytokines in the oviducts and uterine horns are other possible mechanisms induced by Trypanosoma cruzi to infertility. Plasmodium spp. and Trypanosoma brucei spp. cause damage in pituitary gland, hormonal disorders, and decreased semen quality. Entamoeba histolytica infection leads to pelvic pain, salpingitis, tubo-ovarian abscess, and genital ulcers. Cutaneous and visceral leishmaniasis can induce genital lesion, testicular amyloidosis, inflammation of epididymis, prostatitis, and sperm abnormality in human and animals. In addition, some epidemiological studies have reported that rates of protozoan infections in infertile patients are higher than healthy controls. The current review indicates that protozoan parasitic

  3. Disruption of the human gut microbiota following Norovirus infection.

    Directory of Open Access Journals (Sweden)

    Adam M Nelson

    Full Text Available The gut microbiota, the collection of all bacterial members in the intestinal tract, plays a key role in health. Disruption of the indigenous microbiota by a variety of stressors, including antibiotic therapy and intestinal infections, is associated with multiple health problems. We sought to determine if infection with Norovirus disrupts the gut microbiota. Barcoded pyrosequencing of the 16S rRNA-encoding gene was used to characterize the stool microbiota in Norovirus-infected human patients (n = 38. While the microbiota in most infected patients (n = 31 resembled that seen in uninfected healthy controls, a minority of patients (n = 7 possessed a significantly altered microbiota characterized by reduced relative numbers of Bacteriodetes and a corresponding increase in Proteobacteria. In these patients, the increase in Proteobacteria was due to a single operational taxonomic unit (OTU of Escherichia coli. We cultured E. coli from Norovirus-infected patients and characterized them using PCR-ribotyping and virulence factor analysis. Multiple ribotypes were encountered, but none possessed typical virulence factors commonly carried by enteropathogenic E. coli strains. Microbiota disruption and elevated Proteobacteria were not significantly correlated to patient age, gender, sampling time following illness onset, or overall gut inflammation. These results demonstrate that some patients have a disrupted microbiota following Norovirus infection, and therefore may be at elevated risk for long-term health complications.

  4. Human Hendra virus infection causes acute and relapsing encephalitis.

    Science.gov (United States)

    Wong, K T; Robertson, T; Ong, B B; Chong, J W; Yaiw, K C; Wang, L F; Ansford, A J; Tannenberg, A

    2009-06-01

    To study the pathology of two cases of human Hendra virus infection, one with no clinical encephalitis and one with relapsing encephalitis. Autopsy tissues were investigated by light microscopy, immunohistochemistry and in situ hybridization. In the patient with acute pulmonary syndrome but not clinical acute encephalitis, vasculitis was found in the brain, lung, heart and kidney. Occasionally, viral antigens were demonstrated in vascular walls but multinucleated endothelial syncytia were absent. In the lung, there was severe inflammation, necrosis and viral antigens in type II pneumocytes and macrophages. The rare kidney glomerulus showed inflammation and viral antigens in capillary walls and podocytes. Discrete necrotic/vacuolar plaques in the brain parenchyma were associated with antigens and viral RNA. Brain inflammation was mild although CD68(+) microglia/macrophages were significantly increased. Cytoplasmic viral inclusions and antigens and viral RNA in neurones and ependyma suggested viral replication. In the case of relapsing encephalitis, there was severe widespread meningoencephalitis characterized by neuronal loss, macrophages and other inflammatory cells, reactive blood vessels and perivascular cuffing. Antigens and viral RNA were mainly found in neurones. Vasculitis was absent in all the tissues examined. The case of acute Hendra virus infection demonstrated evidence of systemic infection and acute encephalitis. The case of relapsing Hendra virus encephalitis showed no signs of extraneural infection but in the brain, extensive inflammation and infected neurones were observed. Hendra virus can cause acute and relapsing encephalitis and the findings suggest that the pathology and pathogenesis are similar to Nipah virus infection.

  5. Human innate lymphoid cells (ILCs) in filarial infections.

    Science.gov (United States)

    Bonne-Année, S; Nutman, T B

    2018-02-01

    Filarial infections are characteristically chronic and can cause debilitating diseases governed by parasite-induced innate and adaptive immune responses. Filarial parasites traverse or establish niches in the skin (migrating infective larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin (circulating microfilariae) where they intersect with the host immune response. While several studies have demonstrated that filarial parasites and their antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell subsets), T- and B-lymphocytes and skin resident cell populations, the role of innate lymphoid cells during filarial infections has only recently emerged. Despite the identification and characterization of innate lymphoid cells (ILCs) in murine helminth infections, little is actually known about the role of human ILCs during parasitic infections. The focus of this review will be to highlight the composition of ILCs in the skin, lymphatics and blood; where the host-parasite interaction is well-defined and to examine the role of ILCs during filarial infections. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  6. [Transfer factor effectiveness patients with persistent genital human papillomavirus infection].

    Science.gov (United States)

    Morfin-Maciel, Blanca María; Sotelo-Ortiz, Julieta Margarita

    2012-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Most HPV infections are cleared within two years by the immune system. Only in 5% to 10% of infected women the infection persists determining a high risk of developing cervical intraepithelial neoplasia. The transfer factor (TF) or dialyzable leukocyte extract is an immunomodulator that has been successfully used as an adjuvant in the treatment of intracelular infections such as recurrent herpes virus diseases. One daily dose of transfer factor was given for five days and subsequently each week for five weeks to a group of women with persistent genital papillomavirus infection. We included 13 patients, aged 19 to 45 years, with first intercourse between the ages of 14 to 23, and a mean of three sexual partners in their lifetime. All of them had persistent HPV that had been treated before with local and ablative therapeutic options, including cervical freezing, cervical conization, cauterizing loop, imiquimod and podophyllin. Transfer factor was administered daily for 5 days, and subsequently at 7-day intervals for 5 weeks. We found a clinical significant improvement in the gynaecological evaluation of cervical, vaginal, vulvar and perineal lesions. No recurrences have developed for at least 1 year of follow-up. The use of transfer factor in women with HPV showed resolution of genital lesions, without recurrences for at least one year after the treatment was ended.

  7. De Novo Generated Human Red Blood Cells in Humanized Mice Support Plasmodium falciparum Infection.

    Directory of Open Access Journals (Sweden)

    Anburaj Amaladoss

    Full Text Available Immunodeficient mouse-human chimeras provide a powerful approach to study host specific pathogens like Plasmodium (P. falciparum that causes human malaria. Existing mouse models of P. falciparum infection require repeated injections of human red blood cells (RBCs. In addition, clodronate lipsomes and anti-neutrophil antibodies are injected to suppress the clearance of human RBCs by the residual immune system of the immunodeficient mice. Engraftment of NOD-scid Il2rg-/- mice with human hematopoietic stem cells leads to reconstitution of human immune cells. Although human B cell reconstitution is robust and T cell reconstitution is reasonable in the recipient mice, human RBC reconstitution is generally poor or undetectable. The poor reconstitution is mainly the result of a deficiency of appropriate human cytokines that are necessary for the development and maintenance of these cell lineages. Delivery of plasmid DNA encoding human erythropoietin and interleukin-3 into humanized mice by hydrodynamic tail-vein injection resulted in significantly enhanced reconstitution of erythrocytes. With this improved humanized mouse, here we show that P. falciparum infects de novo generated human RBCs, develops into schizonts and causes successive reinvasion. We also show that different parasite strains exhibit variation in their ability to infect these humanized mice. Parasites could be detected by nested PCR in the blood samples of humanized mice infected with P. falciparum K1 and HB3 strains for 3 cycles, whereas in other strains such as 3D7, DD2, 7G8, FCR3 and W2mef parasites could only be detected for 1 cycle. In vivo adaptation of K1 strain further improves the infection efficiency and parasites can be detected by microscopy for 3 cycles. The parasitemia ranges between 0.13 and 0.25% at the first cycle of infection, falls between 0.08 and 0.15% at the second cycle, and drops to barely detectable levels at the third cycle of infection. Compared to existing

  8. Human coronavirus and severe acute respiratory infection in Southern Brazil.

    Science.gov (United States)

    Trombetta, Hygor; Faggion, Heloisa Z; Leotte, Jaqueline; Nogueira, Meri B; Vidal, Luine R R; Raboni, Sonia M

    2016-05-01

    Human coronaviruses (HCoVs) are an important cause of respiratory tract infection and are responsible for causing the common cold in the general population. Thus, adequate surveillance of HCoV is essential. This study aimed to analyze the impact of HCoV infections and their relation to severe acute respiratory infection (SARI) in a hospitalized population in Southern Brazil. A cross-sectional study was conducted at a tertiary care hospital, and assessed inpatients under investigation for SARI by the hospital epidemiology department, and all patients who had nasopharyngeal aspirates collected from January 2012 to December 2013 to detect respiratory viruses (RVs). Viral infection was detected by multiplex reverse transcriptase polymerase chain reaction (RT-PCR), with primers specific to the subtypes HCoV-229E/NL63 and OC43/HKU1. The overall positivity rate was 58.8% (444/755), and HCoVs were detected in 7.6% (n = 34) of positive samples. Children below two years of age were most frequently affected (62%). Comorbidities were more likely to be associated with HCoVs than with other RVs. Immunosuppression was an independent risk factor for HCoV infection (OR = 3.5, 95% CI 1.6-7.6). Dyspnea was less frequently associated with HCoV infection (p infected with HCoV (9%) died from respiratory infection. HCoVs are important respiratory pathogens, especially in hospitalized children under 2 years of age and in immunosuppressed patients. They may account for a small proportion of SARI diagnoses, increased need for mechanical ventilation, intensive care unit admission, and death.

  9. [Human intestinal parasitosis: role of Dientamoeba fragilis in human infections].

    Science.gov (United States)

    Crotti, D; D'Annibale, M L

    2007-01-01

    The Authors report prevalences of intestinal parasitosis among home children and adults during 2002-2004, as in O&P as in acute or prolonged diarrhoea, with particular attention to the role of Dientamoeba fragilis, because often undervalued. Among 3139 subjects, 116 cases of dientamoebiasis (3.7%) and 62 of giardiasis (2.0%) were observed; not typical pathogenic protozoa were reported in 71 cases (2.3%); helminths were identified only in 8 cases (0.5%). Particularly, inside O&P group D. fragilis prevailed in 5.2% of cases (7.8% in adults and 0.5% in children) and G. duodenalis in 2.7% (3.5% and 1.3% respectively); inside acute diarrhoeas D. fragilis prevailed in 1.6% (3.9% and 0.3%) and G. duodenalis in 0.6% (1.3% and 0. 1%); inside prolonged diarrhoeas D. fragilis prevailed in 3.5 % (2.6% and 5.4%) and G. duodenalis in 3.9% (5.8% in adults and never in children). D. fragilis was more often observed among adults (6.3% of all) than among children (0.6%), like G. duodenalis (3.1% versus 0.6%). So, 107 strains of D. fragilis (92.2%) and 53 strains of G. duodenalis (85.5%) were identified in adults. D. fragilis was more frequent among females (24/39 cases, 61.5%, in the last year) while G. duodenalis was more frequent in males (13/23 cases, 56.5%). The Authors conclude underlining the importance of a permanent stain, as Giemsa stain, for a good and complete diagnosis of protozoal intestinal infections, particularly for D. fragilis.

  10. Controlled human infection models for vaccine development: Zika virus debate.

    Science.gov (United States)

    Gopichandran, Vijayaprasad

    2017-10-31

    An ethics panel, convened by the National Institute of Health and other research bodies in the USA, disallowed researchers from the Johns Hopkins University and University of Vermont from performing controlled human infection of healthy volunteers to develop a vaccine against Zika virus infection. The members published their ethical analysis and recommendations in February 2017. They have elaborated on the risks posed by human challenge with Zika virus to the volunteers and other uninvolved third parties and have systematically analysed the social value of such a human challenge experiment. They have also posited some mandatory ethical requirements which should be met before allowing the infection of healthy volunteers with the Zika virus. This commentary elaborates on the debate on the ethics of the human challenge model for the development of a Zika virus vaccine and the role of systematic ethical analysis in protecting the interests of research participants. It further analyses the importance of this debate to the development of a Zika vaccine in India.

  11. Controlled Human Infection for Vaccination Against Streptococcus Pyogenes

    Science.gov (United States)

    2018-01-21

    Streptococcus Pyogenes Pharyngitis; Streptococcus Pharyngitis; Strep Throat; Streptococcus Pyogenes Infection; Group A Streptococcus: B Hemolytic Pharyngitis; Group A Streptococcal Infection; Gram-Positive Bacterial Infections; Bacterial Infections

  12. [Pulmonary complications in children with human immunodeficiency virus infection].

    Science.gov (United States)

    Brockmann V, Pablo; Viviani S, Támara; Peña D, Anamaría

    2007-08-01

    Pulmonary complications in children infected by human immunodeficiency virus (HIV) are common and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). The aim of our study was to review pulmonary diseases and complications in pediatric patients with HIV infection in a large tertiary hospital in Santiago, Chile. We performed a retrospective, descriptive analysis of 17 patients with HIV infection controlled at the Hospital Dr. Sótero del Rio. Respiratory complications/diseases were: overall pneumonia (n: 14), recurrent pneumonia (n: 10), citomegalovirus associated pneumonia (n: 4), Pneumocystis jiroveci associated pneumonia (n: 1) pulmonary tuberculosis (n: 1), lymphoid interstitial pneumonia (n: 3) and chronic pulmonary disease (n: 7). Microorganisms isolated were mostly atypical and frequently associated with severe and chronic pulmonary damage. A high degree of suspicion is required to detect atypical microorganisms promptly, in order to rapidly implement pathogen targeted therapy that could potentially decrease the possibility of sequelae.

  13. Pulmonary disease in patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Lundgren, J D; Orholm, Marianne; Lundgren, B

    1989-01-01

    Pulmonary disease is the most important cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). All parts of the hospital system are expected to be involved in the diagnosis and treatment of HIV infected patients in the coming years. Many different processes...... cause pulmonary disease alone or in combination. Bilateral interstitial infiltrates are the most frequent chest x-ray abnormality and are most frequently caused by infection with Pneumocystis carinii. Cytomegalovirus, Mycobacterium tuberculosis, nonspecific interstitial pneumonitis and pulmonary Kaposi......'s sarcoma are the most important parts of the differential diagnosis. An aggressive approach to the diagnosis of pulmonary disease in this patient population is indicated in order to provide optimal care and assess new therapies....

  14. Kluyvera cryocrescens finger infection: case report and review of eighteen Kluyvera infections in human beings.

    Science.gov (United States)

    West, B C; Vijayan, H; Shekar, R

    1998-11-01

    We report a case of soft tissue infection with Kluyvera cryocrescens and a critical review of Kluyvera infections. A 31-year-old diabetic man used a new chemical for stripping the floor with his bare hands. Two days later he developed a blister on a finger which progressed to tenosynovitis in spite of intravenous nafcillin therapy. After 11 days culture and sensitivity results dictated treatment with intravenous ticarcillin/clavulanic acid. The wound was debrided twice, and later a skin flap was done. Wound cultures became sterile after 7 days of treatment with ticarcillin/clavulanic acid, and he recovered. This case represents the fourth clinical infection with K. cryocrescens and the eighteenth of Kluyvera to be reported. Four others were K. ascorbata, and the remaining ten Kluyvera infections in humans were not identified beyond genus. Our case and review of the 17 previous cases emphasize that while Kluyvera rarely cause disease, these opportunistic Gram-negative bacilli may be virulent in a variety of sites under as yet poorly defined host conditions. Sites of infection varied, but the brain and meninges were not among them. Two patients had diabetes mellitus, none had AIDS, and four died. Once shown clinically to be the cause of an infection, Kluyvera deserve aggressive treatment which acknowledges their ampicillin resistance.

  15. Human Papillomavirus infection and cervical lesions in HIV infected women on antiretroviral treatment in Thailand.

    Science.gov (United States)

    Delory, Tristan; Ngo-Giang-Huong, Nicole; Rangdaeng, Samreung; Chotivanich, Nantasak; Limtrakul, Aram; Putiyanun, Chaiwat; Suriyachai, Pornnapa; Matanasarawut, Wanmanee; Jarupanich, Tapnarong; Liampongsabuddhi, Prateung; Heard, Isabelle; Jourdain, Gonzague; Lallemant, Marc; Le Coeur, Sophie

    2017-05-01

    To estimate the prevalence and factors associated with Human Papillomavirus (HPV) infection, HPV genotypes and cytological/histological high-grade (HSIL+/CIN2+) lesions. We conducted a cross-sectional study within a prospective cohort of HIV-infected women on combination antiretroviral therapy (cART). Cervical specimens were collected for cytology and HPV genotyping (Papillocheck®). Any women with High-Risk-HPV (HR-HPV), and/or potentially HR-HPV (pHR-HPV) and/or ASC-US or higher (ASC-US+) lesions were referred for colposcopy. Factors associated with HR-HPV infection and with HSIL+/CIN2+ lesions were investigated using mixed-effects logistic regression models. 829 women were enrolled: median age 40.4 years, on cART for a median of 6.9 years, median CD4 cell-count 536 cells/mm3, and 788 (96%) with HIV-viral loadwomen (9%) had ASC-US+ and 28 (3%) HSIL+/CIN2+ lesions. HR-HPV infection was independently associated with HSIL+/CIN2+ lesions. The prevalence of HPV infection and of cervical lesions was low. The HPV genotype distribution supports the use of 9-valent vaccine in Thailand. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  16. Natural Gastric Infection with Helicobacter pylori in Monkeys: A Model for Spiral Bacteria Infection in Humans

    Science.gov (United States)

    1994-01-01

    humans and by the persistently Infected and have gastrtis and elevated absence of an accepted animal model. specific IgG levels, all of which may... Gastrtis scoe H. pyon gG Time (mo) Corpus Antrum Corpus Antrum Corpus Antrum ratiod H. pylion-infected (n = 6) 0 1.8 ± 0.5 2.3 ± 0.4 0.7 ± 0.2 1.0...light microscopy)a H. pylon (culture)* Gastrtis score’ H. pylon lgG Time (mo) Corpus Antrum Corpus Antrum Corpus Antrum ratiow H. pyllon-nfected kn = 2

  17. The Pseudomonas aeruginosa opportunistic pathogen and human infections.

    Science.gov (United States)

    de Bentzmann, Sophie; Plésiat, Patrick

    2011-07-01

    Pseudomonas aeruginosa, a Gram-negative environmental species and an opportunistic microorganism, establishes itself in vulnerable patients, such as those with cystic fibrosis or hospitalized in intensive care units. It has become a major cause of nosocomial infections worldwide (about 10% of all such infections in most European Union hospitals) and a serious threat to Public Health. The overuse and misuse of antibiotics have also led to the selection of resistant strains against which very few therapeutic options exist. How an environmental species can cause human infections remains a key question that still needs elucidation despite the incredibly high progress that has been made in the P. aeruginosa biology over the past decades. The workshop belonging to Current trends in Biomedicine series, which was held under the sponsorship of the Universidad International de Andalucia between the 8th and the 10th November 2010 brought in the most recent advances in the environmental life of P. aeruginosa, the human P. aeruginosa infections, the new animal models to study Pseudomonas infections, the new genetic aspects including metabolomics, genomics and bioinformatics and the community lifestyle named biofilm that accounts for P. aeruginosa persistence in humans. This workshop organized by Soeren Molin (Danemark), Juan-Luis Ramos (Spain) and Sophie de Bentzmann (France) gathered 46 researchers coming from 11 European and American countries in a small format and was hosted in the 'Sede Antonio Machado' in Baeza. It was organized in seven sessions covering animal models for P. aeruginosa pathogenesis, resistance to drugs, regulatory potency including small RNA, two component systems, extracytoplasmic function sigma factors and trancriptional regulators, new therapies emerging from dissection of molecular mechanisms, and evolutionary mechanisms of P. aeruginosa strains in patients. © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

  18. Oral Human Papillomavirus Infection: Differences in Prevalence Between Sexes and Concordance With Genital Human Papillomavirus Infection, NHANES 2011 to 2014.

    Science.gov (United States)

    Sonawane, Kalyani; Suk, Ryan; Chiao, Elizabeth Y; Chhatwal, Jagpreet; Qiu, Peihua; Wilkin, Timothy; Nyitray, Alan G; Sikora, Andrew G; Deshmukh, Ashish A

    2017-10-17

    The burden of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is disproportionately high among men, yet empirical evidence regarding the difference in prevalence of oral HPV infection between men and women is limited. Concordance of oral and genital HPV infection among men is unknown. To determine the prevalence of oral HPV infection, as well as the concordance of oral and genital HPV infection, among U.S. men and women. Nationally representative survey. Civilian noninstitutionalized population. Adults aged 18 to 69 years from NHANES (National Health and Nutritional Examination Survey, 2011 to 2014). Oral rinse, penile swab, and vaginal swab specimens were evaluated by polymerase chain reaction followed by type-specific hybridization. The overall prevalence of oral HPV infection was 11.5% (95% CI, 9.8% to 13.1%) in men and 3.2% (CI, 2.7% to 3.8%) in women (equating to 11 million men and 3.2 million women nationwide). High-risk oral HPV infection was more prevalent among men (7.3% [CI, 6.0% to 8.6%]) than women (1.4% [CI, 1.0% to 1.8%]). Oral HPV 16 was 6 times more common in men (1.8% [CI, 1.3% to 2.2%]) than women (0.3% [CI, 0.1% to 0.5%]) (1.7 million men vs. 0.27 million women). Among men and women who reported having same-sex partners, the prevalence of high-risk HPV infection was 12.7% (CI, 7.0% to 18.4%) and 3.6% (CI, 1.4% to 5.9%), respectively. Among men who reported having 2 or more same-sex oral sex partners, the prevalence of high-risk HPV infection was 22.2% (CI, 9.6% to 34.8%). Oral HPV prevalence among men with concurrent genital HPV infection was fourfold greater (19.3%) than among those without it (4.4%). Men had 5.4% (CI, 5.1% to 5.8%) greater predicted probability of high-risk oral HPV infection than women. The predicted probability of high-risk oral HPV infection was greatest among black participants, those who smoked more than 20 cigarettes daily, current marijuana users, and those who reported 16 or more

  19. Infection

    Science.gov (United States)

    2010-09-01

    whether BMPs maintain their osteoinductive capability in infected human wounds. The authors are aware of only one series describing the use of BMP in an...et al. Osteogenic protein-1 induces bone formation in the presence of bacterial infection in a rat intramuscular osteoinduction model. J Orthop Trauma

  20. Network Analysis of Human Genes Influencing Susceptibility to Mycobacterial Infections.

    Directory of Open Access Journals (Sweden)

    Ettie M Lipner

    Full Text Available Tuberculosis and nontuberculous mycobacterial infections constitute a high burden of pulmonary disease in humans, resulting in over 1.5 million deaths per year. Building on the premise that genetic factors influence the instance, progression, and defense of infectious disease, we undertook a systems biology approach to investigate relationships among genetic factors that may play a role in increased susceptibility or control of mycobacterial infections. We combined literature and database mining with network analysis and pathway enrichment analysis to examine genes, pathways, and networks, involved in the human response to Mycobacterium tuberculosis and nontuberculous mycobacterial infections. This approach allowed us to examine functional relationships among reported genes, and to identify novel genes and enriched pathways that may play a role in mycobacterial susceptibility or control. Our findings suggest that the primary pathways and genes influencing mycobacterial infection control involve an interplay between innate and adaptive immune proteins and pathways. Signaling pathways involved in autoimmune disease were significantly enriched as revealed in our networks. Mycobacterial disease susceptibility networks were also examined within the context of gene-chemical relationships, in order to identify putative drugs and nutrients with potential beneficial immunomodulatory or anti-mycobacterial effects.

  1. Human giardiasis in Serbia: asymptomatic vs symptomatic infection*

    Science.gov (United States)

    Nikolić, A.; Klun, I.; Bobić, B.; Ivović, V.; Vujanić, M.; Živković, T.; Djurković-Djaković, O.

    2011-01-01

    Despite the public health importance of giardiasis in all of Europe, reliable data on the incidence and prevalence in Western Balkan Countries (Serbia, Bosnia and Herzegovina, Croatia, Montenegro and FYR Macedonia) are scarce, and the relative contribution of waterborne and food-borne, or person-to-person and/or animalto- person, transmission of human giardiasis is not yet clear. To provide baseline data for the estimation of the public health risk caused by Giardia, we here review the information available on the epidemiological characteristics of asymptomatic and symptomatic human infection in Serbia. Although asymptomatic cases of Giardia represent a major proportion of the total cases of infection, high rates of Giardia infection were found in both asymptomatic and symptomatic populations. No waterborne outbreaks of giardiasis have been reported, and it thus seems that giardiasis mostly occurs sporadically in our milieu. Under such circumstances, control measures to reduce the high prevalence of giardiasis in Serbia have focused on person-to-person transmission, encouraging proper hygiene, but for more targeted intervention measures, studies to identify other risk factors for asymptomatic and symptomatic infections are needed. PMID:21678797

  2. A new approach to establish a cell line with reduced risk of endogenous retroviruses.

    Directory of Open Access Journals (Sweden)

    Aiko Fukuma

    Full Text Available Endogenous retroviruses (ERVs are integrated as DNA proviruses in the genomes of all mammalian species. Several ERVs are replication-competent and produced as fully infectious viruses from host cell. Thus, live-attenuated vaccines and biological substances have been prepared using the cell lines which may produce ERV. Indeed, we recently reported that several commercial live-attenuated vaccines for pets were contaminated with the infectious feline endogenous retrovirus, RD-114. In this study, to establish a cell line for vaccine manufacture with reduced risk of ERVs, we generated a cell line stably expressing human tetherin (Teth-CRFK cells. The release of infectious ERV from Teth-CRFK cells was suppressed to undetectable levels, while the production of parvovirus in Teth-CRFK cells was similar to that in parental CRFK cells. These observations suggest that Teth-CRFK cells will be useful as a cell line for the manufacture of live-attenuated vaccines or biological substances with reduced risk of ERV.

  3. Existence of proviral porcine endogenous retrovirus in fresh and decellularised porcine tissues

    Directory of Open Access Journals (Sweden)

    Prabha S

    2008-01-01

    Full Text Available Purpose: Swine are expected to be utilized as xenograft donors for both whole organ and cellular transplantation. A major concern in using porcine organs for transplantation is the potential of transmission of porcine endogenous retrovirus (PERV. Tissue-engineered or decellularised heart valves have already been implanted in humans and have been marketed by certain companies after Food and Drug Administration (FDA approval. The aim of this study was to examine the existence of porcine endogenous retrovirus (PERV in fresh and decellularised porcine tissues. Methods: Porcine tissues (both fresh and decellularised were analysed using validated assays specific for PERV: polymerase chain reaction (PCR, reverse transcriptase polymerase chain reaction (RT-PCR. Results: PERV specific GAG sequences were found in the porcine heart tissue samples using PCR for DNA and RT- PCR for RNA. All tissue samples (both fresh and treated tissues like aortic valve, pulmonary valve and heart muscle showed the presence of PERV DNA. RT PCR for PERV was positive in all fresh tissues and was found to be negative in decellularised treated tissues. Conclusions: PCR is a rapid, specific test for the detection of PERV virus in xenografts. These findings have demonstrated that the presence of proviral DNA form of PERV in porcine tissues needs to be carefully considered when the infectious disease potential of xenotransplantation is being assessed.

  4. Messenger RNA- versus retrovirus-based induced pluripotent stem cell reprogramming strategies: analysis of genomic integrity.

    Science.gov (United States)

    Steichen, Clara; Luce, Eléanor; Maluenda, Jérôme; Tosca, Lucie; Moreno-Gimeno, Inmaculada; Desterke, Christophe; Dianat, Noushin; Goulinet-Mainot, Sylvie; Awan-Toor, Sarah; Burks, Deborah; Marie, Joëlle; Weber, Anne; Tachdjian, Gérard; Melki, Judith; Dubart-Kupperschmitt, Anne

    2014-06-01

    The use of synthetic messenger RNAs to generate human induced pluripotent stem cells (iPSCs) is particularly appealing for potential regenerative medicine applications, because it overcomes the common drawbacks of DNA-based or virus-based reprogramming strategies, including transgene integration in particular. We compared the genomic integrity of mRNA-derived iPSCs with that of retrovirus-derived iPSCs generated in strictly comparable conditions, by single-nucleotide polymorphism (SNP) and copy number variation (CNV) analyses. We showed that mRNA-derived iPSCs do not differ significantly from the parental fibroblasts in SNP analysis, whereas retrovirus-derived iPSCs do. We found that the number of CNVs seemed independent of the reprogramming method, instead appearing to be clone-dependent. Furthermore, differentiation studies indicated that mRNA-derived iPSCs differentiated efficiently into hepatoblasts and that these cells did not load additional CNVs during differentiation. The integration-free hepatoblasts that were generated constitute a new tool for the study of diseased hepatocytes derived from patients' iPSCs and their use in the context of stem cell-derived hepatocyte transplantation. Our findings also highlight the need to conduct careful studies on genome integrity for the selection of iPSC lines before using them for further applications. ©AlphaMed Press.

  5. Nuclear domain 10 components upregulated via interferon during human cytomegalovirus infection potently regulate viral infection.

    Science.gov (United States)

    Ashley, Caroline L; Glass, Mandy S; Abendroth, Allison; McSharry, Brian P; Slobedman, Barry

    2017-07-01

    Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that causes life-threatening disease in immunocompromised and immunonaïve individuals. Type I interferons (IFNs) are crucial molecules in the innate immune response to HCMV and are also known to upregulate several components of the interchromosomal multiprotein aggregates collectively referred to as nuclear domain 10 (ND10). In the context of herpesvirus infection, ND10 components are known to restrict gene expression. This raises the question as to whether key ND10 components (PML, Sp100 and hDaxx) act as anti-viral IFN-stimulated genes (ISGs) during HCMV infection. In this study, analysis of ND10 component transcription during HCMV infection demonstrated that PML and Sp100 were significantly upregulated whilst hDaxx expression remained unchanged. In cells engineered to block the production of, or response to, type I IFNs, upregulation of PML and Sp100 was not detected during HCMV infection. Furthermore, pre-treatment with an IFN-β neutralizing antibody inhibited upregulation of PML and Sp100 during both infection and treatment with HCMV-infected cell supernatant. The significance of ND10 components functioning as anti-viral ISGs during HCMV infection was determined through knockdown of PML, Sp100 and hDaxx. ND10 knockdown cells were significantly more permissive to HCMV infection, as previously described but, in contrast to control cells, could support HCMV plaque formation following IFN-β pre-treatment. This ability of HCMV to overcome the potently anti-viral effects of IFN-β in ND10 expression deficient cells provides evidence that ND10 component upregulation is a key mediator of the anti-viral activity of IFN-β.

  6. Role of CD4 endocytosis in human immunodeficiency virus infection.

    Science.gov (United States)

    Pelchen-Matthews, A; Clapham, P; Marsh, M

    1995-12-01

    We have analyzed the role of CD4 endocytosis in human immunodeficiency virus (HIV) entry by measuring the infection of HeLa cells expressing various CD4 constructs with endocytosis rates of between 0.2 and 30%/min in a quantitative infectious focus assay. For a number of laboratory-adapted HIV-1 and HIV-2 strains, the highest levels of infection were found on cells with very limited CD4 endocytosis, while cells with efficient CD4 uptake were only poorly infectable, suggesting that CD4 internalization is not required for HIV entry. This was confirmed in a modified assay involving prebinding of HIV-1LAI to HeLa-CD4 cells at 4 degrees C, synchronized virus entry during warming to 37 degrees C, and neutralization of virions remaining at the cell surface with anti-V3 loop antibodies. Warming cells in hypertonic medium inhibited CD4 endocytosis but did not affect the rate or the extent of infection. These studies confirm that HIV infection does not require endocytosis and that laboratory-adapted virus strains can enter HeLa-CD4 cells by fusion at the plasma membrane.

  7. [Hematological changes associated with human immunodeficiency virus (HIV-1) infection].

    Science.gov (United States)

    Møller, T; Hasselbalch, H C

    1993-05-10

    Infection with human immunodeficiency virus type 1 (HIV-1) primarily involves a subgroup of T-lymphocytic cells, but other cell types are also invaded by the virus, including cell lines within the haematopoietic system. Together with infectious, inflammatory and neoplasic processes, invasion of haematopoietic tissue explains the haematological alterations which are seen during the course of infection with HIV-1. Anaemia develops in the large proportion of patients. Thrombocytopenia frequently occurs during the course of the disease, but may be seen in some patients already at the time of diagnosis, where the condition may be misdiagnosed as "idiopathic" thrombocytopenic purpura. Neutropenia is seen in all disease stages, but is most severe in patients with advanced disease. Bone marrow changes include varying degrees of dysplasia in one or more cell lines, which in some patients may mimic a myelodysplastic syndrome. The number of plasma cells is always increased. In many patients the bone marrow stroma exhibits an increased amount of reticular fibres. HIV-1 infection is associated with an increased risk of non-Hodgkin malignant lymphoma. Acute myelogenous leukaemia and myelomatosis have been described in patients with advanced disease. Treatment of the above mentioned haematological abnormalities aims primarily at reducing replication of HIV-1, thereby diminishing suppression of haematopoiesis by the virus infection, and at controlling the opportunistic infections during the course of the disease. Specific antiviral therapy (AZT) is most successful in correcting thrombocytopenia. The possibility of bone marrow suppression mediated by a toxic drug effect should always be considered in this patient group.

  8. Human parasitic meningitis caused by Angiostrongylus cantonensis infection in Taiwan.

    Science.gov (United States)

    Tsai, Hung-Chin; Chen, Yao-Shen; Yen, Chuan-Min

    2013-06-01

    The major cause of eosinophilic meningitis in Taiwan is Angiostrongylus cantonensis. Humans are infected by ingesting terrestrial and freshwater snails and slugs. In 1998 and 1999, two outbreaks of eosinophilic meningitis caused by A. cantonensis infection were reported among 17 adult male immigrant Thai laborers who had eaten raw golden apple snails (Pomacea canaliculata). Another outbreak associated with consuming a health drink consisting of raw vegetable juice was reported in 2001. These adult cases differed from reports in the 1970s and 1980s, in which most of the cases were in children. With improvements in public health and education of foreign laborers, there have since been only sporadic cases in Taiwan. Review of clinical research indicates inconsistent association of Magnetic Resonance Imaging (MRI) results with clinical features of eosinophilic meningitis. MRI features were nonspecific but there was an association between the presence of high brain MRI signal intensities and severity of peripheral and cerebrospinal fluid (CSF) eosinophilia. Inflammatory markers have been identified in the CSF of patients with eosinophilic meningitis caused by A. cantonensis infection, and vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and the matrix metalloproteinase system may be associated with blood-brain barrier disruption. Eosinophilic meningitis caused by A. cantonensis infection is not a reportable disease in Taiwan. It is important that a public advisory and education program be developed to reduce future accidental infection.

  9. Human rhinovirus infection in young African children with acute wheezing

    Directory of Open Access Journals (Sweden)

    Zar Heather J

    2011-03-01

    Full Text Available Abstract Background Infections caused by human rhinoviruses (HRVs are important triggers of wheezing in young children. Wheezy illness has increasingly been recognised as an important cause of morbidity in African children, but there is little information on the contribution of HRV to this. The aim of this study was to determine the role of HRV as a cause of acute wheezing in South African children. Methods Two hundred and twenty children presenting consecutively at a tertiary children's hospital with a wheezing illness from May 2004 to November 2005 were prospectively enrolled. A nasal swab was taken and reverse transcription PCR used to screen the samples for HRV. The presence of human metapneumovirus, human bocavirus and human coronavirus-NL63 was assessed in all samples using PCR-based assays. A general shell vial culture using a pool of monoclonal antibodies was used to detect other common respiratory viruses on 26% of samples. Phylogenetic analysis to determine circulating HRV species was performed on a portion of HRV-positive samples. Categorical characteristics were analysed using Fisher's Exact test. Results HRV was detected in 128 (58.2% of children, most (72% of whom were under 2 years of age. Presenting symptoms between the HRV-positive and negative groups were similar. Most illness was managed with ambulatory therapy, but 45 (35% were hospitalized for treatment and 3 (2% were admitted to intensive care. There were no in-hospital deaths. All 3 species of HRV were detected with HRV-C being the most common (52% followed by HRV-A (37% and HRV-B (11%. Infection with other respiratory viruses occurred in 20/128 (16% of HRV-positive children and in 26/92 (28% of HRV-negative samples. Conclusion HRV may be the commonest viral infection in young South African children with acute wheezing. Infection is associated with mild or moderate clinical disease.

  10. Measuring serum antibody to human papillomavirus following infection or vaccination.

    Science.gov (United States)

    Frazer, Ian H

    2010-06-01

    The family of human papillomaviruses (HPVs) includes more than 130 genotypes, many of which infect the genital tract, and these can be classified as low risk or high risk for induction of genital neoplasia. Two prophylactic vaccines are currently available for the prevention of genital HPV infection: a quadrivalent (Gardasil); Merck & Co. Inc) and a bivalent (Cervarix; GlaxoSmithKline) vaccine. Protection against HPV infection and associated disease is observed for at least 6.4 years following immunization with the bivalent vaccine and for at least 8.5 years with the HPV 16L1 virus-like particle of the quadrivalent vaccine. HPV vaccines induce robust immune memory, as evidenced by recall of responses after revaccination, suggesting that immunization will afford long-lasting protection. An immunological marker for ongoing protection from infection would provide information to help establish best-practice deployment of these vaccines. However, while HPV-specific antibody is likely the major mechanism of protection against HPV infection following immunization, available serological assays provide only a partial characterization of immune status, and no measured immune response has been shown to define immediate or future protection against HPV infection or associated disease. Future research efforts should therefore be directed towards correlating measures of virus-specific immune memory with continued protection against infection with the HPV types in the available vaccines, and towards determining the duration of cross-protection afforded by these vaccines against HPV types other than those incorporated in the vaccines. Copyright (c) 2010. Published by Elsevier Inc.

  11. Serologic evidence of human orthopoxvirus infections in Sierra Leone.

    Science.gov (United States)

    Macneil, Adam; Abel, Jason; Reynolds, Mary G; Lash, Rr; Fonnie, Richard; Kanneh, Lansana D; Robert, Willie; Lungay, Victor K; Goba, Augustine; Moses, Lina M; Damon, Inger K; Karem, Kevin; Bausch, Daniel G

    2011-10-28

    Orthopoxviruses, including variola virus, vaccinia virus, and monkeypox virus, have previously been documented in humans in West Africa, however, no cases of human orthopoxvirus infection have been reported in the region since 1986. We conducted a serosurvey to determine whether human exposure to orthopoxviruses continues to occur in eastern Sierra Leone. To examine evidence of exposure to orthopoxviruses in the Kenema District of Sierra Leone, we collected and tested sera from 1596 persons by IgG ELISA and a subset of 313 by IgM capture ELISA. Eleven persons born after the cessation of smallpox vaccination had high orthopoxvirus-specific IgG values, and an additional 6 persons had positive IgM responses. No geographic clustering was noted. These data suggest that orthopoxviruses continue to circulate in Sierra Leone. Studies aimed at obtaining orthopoxvirus isolates and/or genetic sequences from rodents and symptomatic humans in the area are indicated.

  12. Serologic evidence of human orthopoxvirus infections in Sierra Leone

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    Goba Augustine

    2011-10-01

    Full Text Available Abstract Background Orthopoxviruses, including variola virus, vaccinia virus, and monkeypox virus, have previously been documented in humans in West Africa, however, no cases of human orthopoxvirus infection have been reported in the region since 1986. We conducted a serosurvey to determine whether human exposure to orthopoxviruses continues to occur in eastern Sierra Leone. Findings To examine evidence of exposure to orthopoxviruses in the Kenema District of Sierra Leone, we collected and tested sera from 1596 persons by IgG ELISA and a subset of 313 by IgM capture ELISA. Eleven persons born after the cessation of smallpox vaccination had high orthopoxvirus-specific IgG values, and an additional 6 persons had positive IgM responses. No geographic clustering was noted. Conclusions These data suggest that orthopoxviruses continue to circulate in Sierra Leone. Studies aimed at obtaining orthopoxvirus isolates and/or genetic sequences from rodents and symptomatic humans in the area are indicated.

  13. Defining cell culture conditions to improve human norovirus infectivity assays

    Energy Technology Data Exchange (ETDEWEB)

    Straub, Tim M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hutchison, Janine R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bartholomew, Rachel A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Valdez, Catherine O. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Valentine, Nancy B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Dohnalkova, Alice [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Ozanich, Richard M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bruckner-Lea, Cindy J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2013-01-10

    Significant difficulties remain for determining whether human noroviruses (hNoV) recovered from water, food, and environmental samples are infectious. Three-dimensional tissue culture of human intestinal cells has shown promise in developing an infectivity assay, but reproducibility, even within a single laboratory, remains problematic. From the literature and our observations, we hypothesized that the common factors that leads to more reproducible hNoV infectivity in vitro requires that the cell line be 1) of human gastrointestinal origin, 2) expresses apical microvilli, and 3) be a positive secretor cell line. The C2BBe1 cell line, which is a brush-border producing clone of Caco-2, meets these three criteria. When challenged with Genogroup II viruses, we observed a 2 Log10 increase in viral RNA titer. A passage experiment with GII viruses showed evidence of the ability to propagate hNoV by both reverse transcription quantitative PCR (qRT-PCR) and microscopy. Using 3-D C2BBe1 cells improves reproducibility of the infectivity assay for hNoV, but the assay can still be variable. Two sources of variability include the cells themselves (mixed phenotypes of small and large intestine) and initial titer measurements using quantitative reverse transcription PCR (qRT-PCR) that measures all RNA vs. plaque assays that measure infectious virus.

  14. Ectopic expression of the erythrocyte band 3 anion exchange protein, using a new avian retrovirus vector

    DEFF Research Database (Denmark)

    Fuerstenberg, S; Beug, H; Introna, M

    1990-01-01

    into protein. Using the Escherichia coli beta-galactosidase gene cloned into the vector as a test construct, expression of enzyme activity could be detected in 90 to 95% of transfected target cells and in 80 to 85% of subsequently infected cells. In addition, a cDNA encoding the avian erythrocyte band 3 anion......A retrovirus vector was constructed from the genome of avian erythroblastosis virus ES4. The v-erbA sequences of avian erythroblastosis virus were replaced by those coding for neomycin phosphotransferase, creating a gag-neo fusion protein which provides G418 resistance as a selectable marker. The v......-erbB sequences following the splice acceptor were replaced by a cloning linker allowing insertion of foreign genes. The vector has been tested in conjunction with several helper viruses for the transmission of G418 resistance, titer, stability, transcription, and the transduction and expression of foreign genes...

  15. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Alcendor Donald J

    2012-05-01

    Full Text Available Abstract Background Congenital human cytomegalovirus (HCMV infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV, microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC. However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha, interleukin-1 beta (IL-1beta, and interleukin-6 (IL-6. Pericytes exposed to SBCMV elicited

  16. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Science.gov (United States)

    2012-01-01

    Background Congenital human cytomegalovirus (HCMV) infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR) methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV), microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC). However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin-6 (IL-6). Pericytes exposed to SBCMV elicited higher levels of IL-6

  17. No evidence for XMRV in German CFS and MS patients with fatigue despite the ability of the virus to infect human blood cells in vitro.

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    Oliver Hohn

    Full Text Available BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV, a novel human retrovirus originally identified in prostate cancer tissues, has recently been associated with chronic fatigue syndrome (CFS, a disabling disease of unknown etiology affecting millions of people worldwide. However, several subsequent studies failed to detect the virus in patients suffering from these illnesses or in healthy subjects. Here we report the results of efforts to detect antibody responses and viral sequences in samples from a cohort of German CFS and relapsing remitting multiple sclerosis (MS patients with fatigue symptoms. METHODOLOGY: Blood samples were taken from a cohort of 39 patients fulfilling the Fukuda/CDC criteria (CFS, from 112 patients with an established MS diagnosis and from 40 healthy donors. Fatigue severity in MS patients was assessed using the Fatigue Severity Scale (FSS. Validated Gag- and Env-ELISA assays were used to screen sera for XMRV antibodies. PHA-activated PBMC were cultured for seven days in the presence of IL-2 and DNA isolated from these cultures as well as from co-cultures of PBMC and highly permissive LNCaP cells was analyzed by nested PCR for the presence of the XMRV gag gene. In addition, PBMC cultures were exposed to 22Rv1-derived XMRV to assess infectivity and virus production. CONCLUSION: None of the screened sera from CFS and MS patients or healthy blood donors tested positive for XMRV specific antibodies and all PBMC (and PBMC plus LNCaP cultures remained negative for XMRV sequences by nested PCR. These results argue against an association between XMRV infection and CFS and MS in Germany. However, we could confirm that PBMC cultures from healthy donors and from CFS patients can be experimentally infected by XMRV, resulting in the release of low levels of transmittable virus.

  18. Incidence and persistence of carcinogenic genital human papillomavirus infections in young women with or without Chlamydia trachomatis co-infection

    NARCIS (Netherlands)

    Vriend, Henrike J.; Bogaards, Johannes A.; van Bergen, Jan E. A. M.; Brink, Antoinette A. T. P.; van den Broek, Ingrid V. F.; Hoebe, Christian J. P. A.; King, Audrey J.; van der Sande, Marianne A. B.; Wolffs, Petra F. G.; de Melker, Hester E.

    2015-01-01

    We assessed whether infection with chlamydia increases the incidence of carcinogenic human papillomavirus (HPV) infections and if HPV persistence is affected by chlamydia co-infection. For 1982 women (16-29 years-old) participating in two consecutive rounds of a chlamydia screening implementation

  19. Ubiquitin is part of the retrovirus budding machinery

    Science.gov (United States)

    Patnaik, Akash; Chau, Vincent; Wills, John W.

    2000-11-01

    Retroviruses contain relatively large amounts of ubiquitin, but the significance of this finding has been unknown. Here, we show that drugs that are known to reduce the level of free ubiquitin in the cell dramatically reduced the release of Rous sarcoma virus, an avian retrovirus. This effect was suppressed by overexpressing ubiquitin and also by directly fusing ubiquitin to the C terminus of Gag, the viral protein that directs budding and particle release. The block to budding was found to be at the plasma membrane, and electron microscopy revealed that the reduced level of ubiquitin results in a failure of mature virus particles to separate from each other and from the plasma membrane during budding. These data indicate that ubiquitin is actually part of the budding machinery.

  20. Pinpointing retrovirus entry sites in cells expressing alternatively spliced receptor isoforms by single virus imaging.

    Science.gov (United States)

    Padilla-Parra, Sergi; Marin, Mariana; Kondo, Naoyuki; Melikyan, Gregory B

    2014-06-16

    The majority of viruses enter host cells via endocytosis. Current knowledge of viral entry pathways is largely based upon infectivity measurements following genetic and/or pharmacological interventions that disrupt vesicular trafficking and maturation. Imaging of single virus entry in living cells provides a powerful means to delineate viral trafficking pathways and entry sites under physiological conditions. Here, we visualized single avian retrovirus co-trafficking with markers for early (Rab5) and late (Rab7) endosomes, acidification of endosomal lumen and the resulting viral fusion measured by the viral content release into the cytoplasm. Virus-carrying vesicles either merged with the existing Rab5-positive early endosomes or slowly accumulated Rab5. The Rab5 recruitment to virus-carrying endosomes correlated with acidification of their lumen. Viral fusion occurred either in early (Rab5-positive) or intermediate (Rab5- and Rab7-positive) compartments. Interestingly, different isoforms of the cognate receptor directed virus entry from distinct endosomes. In cells expressing the transmembrane receptor, viruses preferentially entered and fused with slowly maturing early endosomes prior to accumulation of Rab7. By comparison, in cells expressing the GPI-anchored receptor, viruses entered both slowly and quickly maturing endosomes and fused with early (Rab5-positive) and intermediate (Rab5- and Rab7-positive) compartments. Since the rate of low pH-triggered fusion was independent of the receptor isoform, we concluded that the sites of virus entry are determined by the kinetic competition between endosome maturation and viral fusion. Our findings demonstrate the ability of this retrovirus to enter cells via alternative endocytic pathways and establish infection by releasing its content from distinct endosomal compartments.

  1. World Reference Center for Arboviruses and Retroviruses

    Science.gov (United States)

    1988-05-01

    orbiviruses have 10- 12 RNA segments which can reassort and thus they present an analogy to sexual reproduction in other organisms. In these experiments...the Instituto Nacional de Salud . YARU will receive HIV positive cultures for confirmation of identity of HIV isolates, and will store infected cells in

  2. Susceptibility of recombinant porcine endogenous retrovirus reverse transcriptase to nucleoside and non-nucleoside inhibitors.

    Science.gov (United States)

    Wilhelm, M; Fishman, J A; Pontikis, R; Aubertin, A M; Wilhelm, F X

    2002-12-01

    Transplantation of organs, tissues or cells from pigs to humans could be a potential solution to the shortage of human organs for transplantation. Porcine endogenous retroviruses (PERVs) remain a major safety concern for porcine xenotransplantation. Thus, finding drugs that could be used as virological prophylaxis (or therapy) against PERV replication would be desirable. One of the most effective ways to block retroviral multiplication is to inhibit the enzyme reverse transcriptase (RT) which catalyzes the reverse transcription of viral RNA to proviral double-stranded DNA. We report here the cloning and expression of PERV RT and its susceptibility to several inhibitors. Our data demonstrate PERV susceptibility in vitro to the triphosphorylated nucleoside analog of zidovudine (AZT) and to ddGTP and to a lesser extent to ddTTP but almost no susceptibility to the non-nucleoside RT inhibitors tested.

  3. The Laboratory Diagnosis of Genital Human Papillomavirus Infections

    Directory of Open Access Journals (Sweden)

    François Coutlee

    2005-01-01

    Full Text Available Human papillomaviruses (HPVs are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women.

  4. [Animals as a potential source of human fungal infections].

    Science.gov (United States)

    Dworecka-Kaszak, Bozena

    2008-01-01

    Changing environment is a reason, that many saprotrophic fungi became opportunists and in the end also maybe a pathogenic. Host specific adaptation is not so strong among fungi, so there are many common fungal pathogens for people and for animals. Animals suffering from dermatomycosis are well recognize as source of human superficial mycoses. Breeding of different exotic animals such as parrots, various Reptiles and Amphibians, miniature Rodents and keeping them as a pets in the peoples houses, have become more and more popular in the recent years. This article is shortly presenting which animals maybe a potential source of fungal infections for humans. Looking for the other mycoses as systemic mycoses, especially candidiasis or aspergilosis there are no data, which allow excluding sick animals as a source of infection for human, even if those deep mycoses have endogenic reactivation mechanism. Immunocompromised people are in high-risk group when they take care of animals. Another important source of potentially pathogenic, mostly air-born fungi may be animal use in experimental laboratory work. During the experiments is possible that laboratory workers maybe hurt and these animals and their environment, food and house boxes could be the possible source of microorganisms, pathogenic for humans or other animals. Unusual way to inoculate these potentially pathogens into the skin of laboratory personnel may cause granulomatous, local lesions on their hands.

  5. A Computational Model for Predicting RNase H Domain of Retrovirus.

    Directory of Open Access Journals (Sweden)

    Sijia Wu

    Full Text Available RNase H (RNH is a pivotal domain in retrovirus to cleave the DNA-RNA hybrid for continuing retroviral replication. The crucial role indicates that RNH is a promising drug target for therapeutic intervention. However, annotated RNHs in UniProtKB database have still been insufficient for a good understanding of their statistical characteristics so far. In this work, a computational RNH model was proposed to annotate new putative RNHs (np-RNHs in the retroviruses. It basically predicts RNH domains through recognizing their start and end sites separately with SVM method. The classification accuracy rates are 100%, 99.01% and 97.52% respectively corresponding to jack-knife, 10-fold cross-validation and 5-fold cross-validation test. Subsequently, this model discovered 14,033 np-RNHs after scanning sequences without RNH annotations. All these predicted np-RNHs and annotated RNHs were employed to analyze the length, hydrophobicity and evolutionary relationship of RNH domains. They are all related to retroviral genera, which validates the classification of retroviruses to a certain degree. In the end, a software tool was designed for the application of our prediction model. The software together with datasets involved in this paper can be available for free download at https://sourceforge.net/projects/rhtool/files/?source=navbar.

  6. A Computational Model for Predicting RNase H Domain of Retrovirus.

    Science.gov (United States)

    Wu, Sijia; Zhang, Xinman; Han, Jiuqiang

    2016-01-01

    RNase H (RNH) is a pivotal domain in retrovirus to cleave the DNA-RNA hybrid for continuing retroviral replication. The crucial role indicates that RNH is a promising drug target for therapeutic intervention. However, annotated RNHs in UniProtKB database have still been insufficient for a good understanding of their statistical characteristics so far. In this work, a computational RNH model was proposed to annotate new putative RNHs (np-RNHs) in the retroviruses. It basically predicts RNH domains through recognizing their start and end sites separately with SVM method. The classification accuracy rates are 100%, 99.01% and 97.52% respectively corresponding to jack-knife, 10-fold cross-validation and 5-fold cross-validation test. Subsequently, this model discovered 14,033 np-RNHs after scanning sequences without RNH annotations. All these predicted np-RNHs and annotated RNHs were employed to analyze the length, hydrophobicity and evolutionary relationship of RNH domains. They are all related to retroviral genera, which validates the classification of retroviruses to a certain degree. In the end, a software tool was designed for the application of our prediction model. The software together with datasets involved in this paper can be available for free download at https://sourceforge.net/projects/rhtool/files/?source=navbar.

  7. Comparing New-Generation Candidate Vaccines against Human Orthopoxvirus Infections.

    Science.gov (United States)

    Maksyutov, R A; Yakubitskyi, S N; Kolosova, I V; Shchelkunov, S N

    2017-01-01

    The lack of immunity to the variola virus in the population, increasingly more frequent cases of human orthopoxvirus infection, and increased risk of the use of the variola virus (VARV) as a bioterrorism agent call for the development of modern, safe vaccines against orthopoxvirus infections. We previously developed a polyvalent DNA vaccine based on five VARV antigens and an attenuated variant of the vaccinia virus (VACV) with targeted deletion of six genes (VACΔ6). Independent experiments demonstrated that triple immunization with a DNA vaccine and double immunization with VACΔ6 provide protection to mice against a lethal dose (10 LD50) of the ectromelia virus (ECTV), which is highly pathogenic for mice. The present work was aimed at comparing the immunity to smallpox generated by various immunization protocols using the DNA vaccine and VACΔ6. It has been established that immunization of mice with a polyvalent DNA vaccine, followed by boosting with recombinant VACΔ6, as well as double immunization with VACΔ6, induces production of VACV-neutralizing antibodies and provides protection to mice against a 150 LD50 dose of ECTV. The proposed immunization protocols can be used to develop safe vaccination strategies against smallpox and other human orthopoxvirus infections.

  8. Absence of human cytomegalovirus infection in childhood brain tumors.

    Science.gov (United States)

    Sardi, Iacopo; Lucchesi, Maurizio; Becciani, Sabrina; Facchini, Ludovica; Guidi, Milena; Buccoliero, Anna Maria; Moriondo, Maria; Baroni, Gianna; Stival, Alessia; Farina, Silvia; Genitori, Lorenzo; de Martino, Maurizio

    2015-01-01

    Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients' neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors.

  9. The Epidemiology of Human Papillomavirus Infection and Cervical Cancer

    Directory of Open Access Journals (Sweden)

    F. Xavier Bosch

    2007-01-01

    Full Text Available Cervical cancer has been recognized as a rare outcome of a common Sexually Transmitted Infection (STI. The etiologic association is restricted to a limited number of viral types of the family of the Human Papillomaviruses (HPVs. The association is causal in nature and under optimal testing systems, HPV DNA can be identified in all specimens of invasive cervical cancer. As a consequence, it has been claimed that HPV infection is a necessary cause of cervical cancer. The evidence is consistent worldwide and implies both the Squamous Cell Carcinomas (SCC, the adenocarcinomas and the vast majority (i.e. > 95% of the immediate precursors, namely High Grade Squamous Intraepithelial Lesions (HSIL/Cervical Intraepithelial Neoplasia 3 (CIN3/Carcinoma in situ. Co-factors that modify the risk among HPV DNA positive women include the use of oral contraceptives (OC for five or more years, smoking, high parity (five or more full term pregnancies and previous exposure to other sexually transmitted diseases such as Chlamydia Trachomatis (CT and Herpes Simplex Virus type 2 (HSV-2. Women exposed to the Human Immunodeficiency Virus (HIV are at high risk for HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer.

  10. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Directory of Open Access Journals (Sweden)

    Malgorzata Bienkowska-Haba

    2009-07-01

    Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  11. Early Trypanosoma cruzi Infection Reprograms Human Epithelial Cells

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    María Laura Chiribao

    2014-01-01

    Full Text Available Trypanosoma cruzi, the causative agent of Chagas disease, has the peculiarity, when compared with other intracellular parasites, that it is able to invade almost any type of cell. This property makes Chagas a complex parasitic disease in terms of prophylaxis and therapeutics. The identification of key host cellular factors that play a role in the T. cruzi invasion is important for the understanding of disease pathogenesis. In Chagas disease, most of the focus is on the response of macrophages and cardiomyocytes, since they are responsible for host defenses and cardiac lesions, respectively. In the present work, we studied the early response to infection of T. cruzi in human epithelial cells, which constitute the first barrier for establishment of infection. These studies identified up to 1700 significantly altered genes regulated by the immediate infection. The global analysis indicates that cells are literally reprogrammed by T. cruzi, which affects cellular stress responses (neutrophil chemotaxis, DNA damage response, a great number of transcription factors (including the majority of NFκB family members, and host metabolism (cholesterol, fatty acids, and phospholipids. These results raise the possibility that early host cell reprogramming is exploited by the parasite to establish the initial infection and posterior systemic dissemination.

  12. Human papillomavirus infection and cervical cancer in Latin America.

    Science.gov (United States)

    Reeves, W C; Brinton, L A; García, M; Brenes, M M; Herrero, R; Gaitán, E; Tenorio, F; de Britton, R C; Rawls, W E

    1989-06-01

    To evaluate a possible association between infection with human papillomavirus (HPV) and cervical cancer, we performed a multicenter case-control study in Latin America of 759 cases of invasive cervical cancer and 1467 randomly selected age-matched controls. Demographic, sexual, behavioral, and other clinical data were obtained by interview, and HPV DNA was assayed in cervical-swab specimens with use of filter in situ hybridization. Cervical infection with HPV 16 or 18 or both was strongly associated with cervical cancer. HPV DNA was detected in 62 percent of the cases but only 32 percent of the controls, and the relative risk of cancer increased from 2.1 (95 percent confidence interval, 1.6 to 2.8) to 9.1 (6.1 to 13.6) with hybridization reactions of increasing strength. Although the number of sexual partners, age at first intercourse, number of live births, and Pap-smear history were also significant risk factors, the strong associations between infection with HPV 16 or 18 or both and cervical cancer persisted after we adjusted for these variables. These observations are consistent with the hypothesis that genital infection with HPV 16 or 18 may have a role in the pathogenesis of cervical cancer. Other well-known risk factors were also identified in the study, but they did not affect the association between HPV and cervical cancer.

  13. Systemic fungal infections in patients with human inmunodeficiency virus.

    Science.gov (United States)

    Rodríguez-Cerdeira, C; Arenas, R; Moreno-Coutiño, G; Vásquez, E; Fernández, R; Chang, P

    2014-01-01

    Histoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum. In immunocompromised patients, primary pulmonary infection can spread to the skin and meninges. Clinical manifestations appear in patients with a CD4(+) lymphocyte count of less than 150 cells/μL. Coccidioidomycosis is a systemic mycosis caused by Coccidioides immitis and Coccidioides posadasii. It can present as diffuse pulmonary disease or as a disseminated form primarily affecting the central nervous system, the bones, and the skin. Cryptococcosis is caused by Cryptococcus neoformans (var. neoformans and var. grubii) and Cryptococcus gattii, which are members of the Cryptococcus species complex and have 5 serotypes: A, B, C, D, and AD. It is a common opportunistic infection in patients with human immunodeficiency virus (HIV)/AIDS, even those receiving antiretroviral therapy. Histopathologic examination and culture of samples from any suspicious lesions are essential for the correct diagnosis of systemic fungal infections in patients with HIV/AIDS. Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.

  14. Human papillomavirus infection and esophageal cancer: a case report

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    Miguel A. Serra Valdés

    2012-10-01

    Full Text Available Introduction. Currently over 216 types of human papillomavirus (HPV have been reported, but only 100 have been fully sequenced. They are able to infect cells of the basal layer of any epithelium. Evidence of HPV oncogenicity has been found. Objective. To describe a case of esophageal HPV infection associated to cancer of the esophagus. Case report. 63 years-old, African and rural origin, single, female housewife with the habit of smoking and frequent ingestion of alcohol. Four months before the diagnosis was established, the patient began to gradually develop dysphagia to solids and weight loss. Upper endoscopy shows a proliferative ulcerated lesion in the middle third of the esophagus. Biopsy is consistent with esophageal squamous cell carcinoma. Cytology is suggestive of papillomavirus infection. Discussion. Prior esophageal papillomatosis and other risk factors contributed to the occurrence of esophageal carcinoma. Histopathology was consistent with the diagnosis of squamous cell carcinoma probably caused by HPV infection. Conclusion. The association between papilloma virus and esophageal cancer is rare but can be diagnosed if it is suspected and other risk factors are present, as well as if there is access to modern diagnostic means.

  15. HIV-1 Vpu promotes release and prevents endocytosis of nascent retrovirus particles from the plasma membrane.

    Directory of Open Access Journals (Sweden)

    2006-05-01

    Full Text Available The human immunodeficiency virus (HIV type-1 viral protein U (Vpu protein enhances the release of diverse retroviruses from human, but not monkey, cells and is thought to do so by ablating a dominant restriction to particle release. Here, we determined how Vpu expression affects the subcellular distribution of HIV-1 and murine leukemia virus (MLV Gag proteins in human cells where Vpu is, or is not, required for efficient particle release. In HeLa cells, where Vpu enhances HIV-1 and MLV release approximately 10-fold, concentrations of HIV-1 Gag and MLV Gag fused to cyan fluorescent protein (CFP were initially detected at the plasma membrane, but then accumulated over time in early and late endosomes. Endosomal accumulation of Gag-CFP was prevented by Vpu expression and, importantly, inhibition of plasma membrane to early endosome transport by dominant negative mutants of Rab5a, dynamin, and EPS-15. Additionally, accumulation of both HIV and MLV Gag in endosomes required a functional late-budding domain. In human HOS cells, where HIV-1 and MLV release was efficient even in the absence of Vpu, Gag proteins were localized predominantly at the plasma membrane, irrespective of Vpu expression or manipulation of endocytic transport. While these data indicated that Vpu inhibits nascent virion endocytosis, Vpu did not affect transferrin endocytosis. Moreover, inhibition of endocytosis did not restore Vpu-defective HIV-1 release in HeLa cells, but instead resulted in accumulation of mature virions that could be released from the cell surface by protease treatment. Thus, these findings suggest that a specific activity that is present in HeLa cells, but not in HOS cells, and is counteracted by Vpu, traps assembled retrovirus particles at the cell surface. This entrapment leads to subsequent endocytosis by a Rab5a- and clathrin-dependent mechanism and intracellular sequestration of virions in endosomes.

  16. World Reference Center for Arboviruses and Retroviruses

    Science.gov (United States)

    1989-05-01

    spot slides of VSV Indiana strains grown in a pig kidney line (Instituto Biologico Rim Suino-2). The monoclonal antibodies were designed to be specific... control of disease. The methodology will also permit identification of viral factors which influence the severity of dengue infection. Primer extension...test for their response to 17D yellow fever vaccine while they are taking chloroquine. Control subjects are also vaccinated and do not receive

  17. Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques.

    Science.gov (United States)

    Santra, Sampa; Tomaras, Georgia D; Warrier, Ranjit; Nicely, Nathan I; Liao, Hua-Xin; Pollara, Justin; Liu, Pinghuang; Alam, S Munir; Zhang, Ruijun; Cocklin, Sarah L; Shen, Xiaoying; Duffy, Ryan; Xia, Shi-Mao; Schutte, Robert J; Pemble Iv, Charles W; Dennison, S Moses; Li, Hui; Chao, Andrew; Vidnovic, Kora; Evans, Abbey; Klein, Katja; Kumar, Amit; Robinson, James; Landucci, Gary; Forthal, Donald N; Montefiori, David C; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; Robb, Merlin L; Michael, Nelson L; Kim, Jerome H; Soderberg, Kelly A; Giorgi, Elena E; Blair, Lily; Korber, Bette T; Moog, Christiane; Shattock, Robin J; Letvin, Norman L; Schmitz, Joern E; Moody, M A; Gao, Feng; Ferrari, Guido; Shaw, George M; Haynes, Barton F

    2015-08-01

    HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.

  18. A Case of Fatal Congenital Human Immunodeficiency Virus Infection

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    Halil Uğur Hatipoğlu

    2016-06-01

    Full Text Available Acquired immune deficiency syndrome is a clinical condition caused by human immunodeficiency virus (HIV which can be transmitted either vertically or horizontally. More than 90% of children living with HIV in developing countries have been infected through mother to child transmission during pregnancy, around the time of birth, or through breastfeeding. In order to reduce the number of infected children, increasing emphasis should be placed on preventing mother to child transmission programs with the use of antiretroviral medications in the pregnant woman during pregnancy and at delivery and, starting immediately after birth for the exposed infant. Here, we present the case of a 60-day-old infant heavily immunocompromised due to an extremely high viral burden of HIV, which was acquired perinatally from an undiagnosed and untreated mother, leading to severe bronchopneumonia, sepsis, septic shock and death.

  19. Treatment model of dengue hemorrhagic fever infection in human body

    Science.gov (United States)

    Handayani, D.; Nuraini, N.; Primasari, N.; Wijaya, K. P.

    2014-03-01

    The treatment model of DHF presented in this paper involves the dynamic of five time-dependent compartments, i.e. susceptible, infected, free virus particle, immune cell, and haematocrit level. The treatment model is investigated based on normalization of haematocrit level, which is expressed as intravenous fluid infusion control. We analyze the stability of the disease free equilibrium and the endemic equilibrium. The numerical simulations will explain the dynamic of each compartment in human body. These results show particularly that infected compartment and free virus particle compartment are tend to be vanished in two weeks after the onset of dengue virus. However, these simulation results also show that without the treatment, the haematocrit level will decrease even though not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control.

  20. Human Dectin-1 Deficiency and Mucocutaneous Fungal Infections

    Science.gov (United States)

    Ferwerda, Bart; Ferwerda, Gerben; Plantinga, Theo S.; Willment, Janet A.; van Spriel, Annemiek B.; Venselaar, Hanka; Elbers, Clara C.; Johnson, Melissa D.; Cambi, Alessandra; Huysamen, Cristal; Jacobs, Liesbeth; Jansen, Trees; Verheijen, Karlijn; Masthoff, Laury; Morré, Servaas A.; Vriend, Gert; Williams, David L.; Perfect, John R.; Joosten, Leo A.B.; Wijmenga, Cisca; van der Meer, Jos W.M.; Adema, Gosse J.; Kullberg, Bart Jan; Brown, Gordon D.; Netea, Mihai G.

    2009-01-01

    SUMMARY Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family in which four women who were affected by either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop-codon mutation Tyr238X in the β-glucan receptor dectin-1. The mutated form of dectin-1 was poorly expressed, did not mediate β-glucan binding, and led to defective production of cytokines (interleukin-17, tumor necrosis factor, and interleukin-6) after stimulation with β-glucan or Candida albicans. In contrast, fungal phagocytosis and fungal killing were normal in the patients, explaining why dectin-1 deficiency was not associated with invasive fungal infections and highlighting the specific role of dectin-1 in human mucosal antifungal defense. PMID:19864674