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Sample records for virus siv infection

  1. Experimental Oral Herpes Simplex Virus-1 (HSV-1 Co-infection in Simian Immunodeficiency Virus (SIV-Infected Rhesus Macaques

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    Meropi Aravantinou

    2017-12-01

    Full Text Available Herpes simplex virus 1 and 2 (HSV-1/2 similarly initiate infection in mucosal epithelia and establish lifelong neuronal latency. Anogenital HSV-2 infection augments the risk for sexual human immunodeficiency virus (HIV transmission and is associated with higher HIV viral loads. However, whether oral HSV-1 infection contributes to oral HIV susceptibility, viremia, or oral complications of HIV infection is unknown. Appropriate non-human primate (NHP models would facilitate this investigation, yet there are no published studies of HSV-1/SIV co-infection in NHPs. Thus, we performed a pilot study for an oral HSV-1 infection model in SIV-infected rhesus macaques to describe the feasibility of the modeling and resultant immunological changes. Three SIV-infected, clinically healthy macaques became HSV-1-infected by inoculation with 4 × 108 pfu HSV-1 McKrae on buccal, tongue, gingiva, and tonsils after gentle abrasion. HSV-1 DNA was shed in oral swabs for up to 21 days, and shedding recurred in association with intra-oral lesions after periods of no shedding during 56 days of follow up. HSV-1 DNA was detected in explant cultures of trigeminal ganglia collected at euthanasia on day 56. In the macaque with lowest baseline SIV viremia, SIV plasma RNA increased following HSV-1 infection. One macaque exhibited an acute pro-inflammatory response, and all three animals experienced T cell activation and mobilization in blood. However, T cell and antibody responses to HSV-1 were low and atypical. Through rigorous assessesments, this study finds that the virulent HSV-1 strain McKrae resulted in a low level HSV-1 infection that elicited modest immune responses and transiently modulated SIV infection.

  2. Acute SIV infection in sooty mangabey monkeys is characterized by rapid virus clearance from lymph nodes and absence of productive infection in germinal centers.

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    Martinot, Amanda J; Meythaler, Mareike; Pozzi, Lu-Ann; Dalecki Boisvert, Karen; Knight, Heather; Walsh, Dennis; Westmoreland, Susan; Anderson, Daniel C; Kaur, Amitinder; O'Neil, Shawn P

    2013-01-01

    Lymphoid tissue immunopathology is a characteristic feature of chronic HIV/SIV infection in AIDS-susceptible species, but is absent in SIV-infected natural hosts. To investigate factors contributing to this difference, we compared germinal center development and SIV RNA distribution in peripheral lymph nodes during primary SIV infection of the natural host sooty mangabey and the non-natural host pig-tailed macaque. Although SIV-infected cells were detected in the lymph node of both species at two weeks post infection, they were confined to the lymph node paracortex in immune-competent mangabeys but were seen in both the paracortex and the germinal center of SIV-infected macaques. By six weeks post infection, SIV-infected cells were no longer detected in the lymph node of sooty mangabeys. The difference in localization and rate of disappearance of SIV-infected cells between the two species was associated with trapping of cell-free virus on follicular dendritic cells and higher numbers of germinal center CD4(+) T lymphocytes in macaques post SIV infection. Our data suggests that fundamental differences in the germinal center microenvironment prevent productive SIV infection within the lymph node germinal centers of natural hosts contributing to sustained immune competency.

  3. Acute SIV infection in sooty mangabey monkeys is characterized by rapid virus clearance from lymph nodes and absence of productive infection in germinal centers.

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    Amanda J Martinot

    Full Text Available Lymphoid tissue immunopathology is a characteristic feature of chronic HIV/SIV infection in AIDS-susceptible species, but is absent in SIV-infected natural hosts. To investigate factors contributing to this difference, we compared germinal center development and SIV RNA distribution in peripheral lymph nodes during primary SIV infection of the natural host sooty mangabey and the non-natural host pig-tailed macaque. Although SIV-infected cells were detected in the lymph node of both species at two weeks post infection, they were confined to the lymph node paracortex in immune-competent mangabeys but were seen in both the paracortex and the germinal center of SIV-infected macaques. By six weeks post infection, SIV-infected cells were no longer detected in the lymph node of sooty mangabeys. The difference in localization and rate of disappearance of SIV-infected cells between the two species was associated with trapping of cell-free virus on follicular dendritic cells and higher numbers of germinal center CD4(+ T lymphocytes in macaques post SIV infection. Our data suggests that fundamental differences in the germinal center microenvironment prevent productive SIV infection within the lymph node germinal centers of natural hosts contributing to sustained immune competency.

  4. High Rate of Simian Immunodeficiency Virus (SIV Infections in Wild Chimpanzees in Northeastern Gabon

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    Vanina Boué

    2015-09-01

    Full Text Available The emergence of HIV-1 groups M, N, O, and P is the result of four independent cross-species transmissions between chimpanzees (cpz and gorillas (gor from central/south Cameroon and humans respectively. Although the first two SIVcpz were identified in wild-born captive chimpanzees in Gabon in 1989, no study has been conducted so far in wild chimpanzees in Gabon. To document the SIVcpz infection rate, genetic diversity, and routes of virus transmission, we analyzed 1458 faecal samples collected in 16 different locations across the country, and we conducted follow-up missions in two of them. We found 380 SIV antibody positive samples in 6 different locations in the north and northeast. We determined the number of individuals collected by microsatellite analysis and obtained an adjusted SIV prevalence of 39.45%. We performed parental analysis to investigate viral spread between and within communities and found that SIVs were epidemiologically linked and were transmitted by both horizontal and vertical routes. We amplified pol and gp41 fragments and obtained 57 new SIVcpzPtt strains from three sites. All strains, but one, clustered together within a specific phylogeographic clade. Given that these SIV positive samples have been collected nearby villages and that humans continue to encroach in ape’s territories, the emergence of a new HIV in this area needs to be considered.

  5. Simian immunodeficiency virus (SIV)-specific CD8+ cytotoxic T lymphocyte responses of naive and vaccinated cynomolgus macaques infected with (SIV)mac32H(J5): quantitative analysis by in vitro antigenic stimulation.

    NARCIS (Netherlands)

    A.M. Geretti (Anna Maria); E.G.J. Hulskotte (Ellen); M.E.M. Dings (Marlinda); C.A. van Baalen (Carel); G. van Amerongen (Geert); A.D.M.E. Osterhaus (Albert)

    1997-01-01

    textabstractDetailed analyses of simian immunodeficiency virus (SIV)-specific cytotoxic T lymphocyte (CTL) responses in vaccinated and infected macaques may help to clarify the role of CTL immunity in protection against lentiviruses. Here, the optimal conditions for the measurement of SIV

  6. Limited contribution of mucosal IgA to Simian immunodeficiency virus (SIV)-specific neutralizing antibody response and virus envelope evolution in breast milk of SIV-infected, lactating rhesus monkeys.

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    Permar, Sallie R; Wilks, Andrew B; Ehlinger, Elizabeth P; Kang, Helen H; Mahlokozera, Tatenda; Coffey, Rory T; Carville, Angela; Letvin, Norman L; Seaman, Michael S

    2010-08-01

    Breast milk transmission of human immunodeficiency virus (HIV) remains an important mode of infant HIV acquisition. Interestingly, the majority of infants remain uninfected during prolonged virus exposure via breastfeeding, raising the possibility that immune components in milk prevent mucosal virus transmission. HIV-specific antibody responses are detectable in the milk of HIV-infected women and simian immunodeficiency virus (SIV)-infected monkeys; however, the role of these humoral responses in virus neutralization and local virus quasispecies evolution has not been characterized. In this study, four lactating rhesus monkeys were inoculated with SIVmac251 and monitored for SIV envelope-specific humoral responses and virus evolution in milk and plasma throughout infection. While the kinetics and breadth of the SIV-specific IgG and IgA responses in milk were similar to those in plasma, the magnitude of the milk responses was considerably lower than that of the plasma responses. Furthermore, a neutralizing antibody response against the inoculation virus was not detected in milk samples at 1 year after infection, despite a measurable autologous neutralizing antibody response in plasma samples obtained from three of four monkeys. Interestingly, while IgA is the predominant immunoglobulin in milk, the milk SIV envelope-specific IgA response was lower in magnitude and demonstrated more limited neutralizing capacity against a T-cell line-adapted SIV compared to those of the milk IgG response. Finally, amino acid mutations in the envelope gene product of SIV variants in milk and plasma samples occurred in similar numbers and at similar positions, indicating that the humoral immune pressure in milk does not drive distinct virus evolution in the breast milk compartment.

  7. Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

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    Simon, Liz; Song, Keijing; Vande Stouwe, Curtis; Hollenbach, Andrew; Amedee, Angela; Mohan, Mahesh; Winsauer, Peter; Molina, Patricia

    2016-03-01

    Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

  8. SIV Infection of Lung Macrophages.

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    Li, Yue; Kang, Guobin; Duan, Lijie; Lu, Wuxun; Katze, Michael G; Lewis, Mark G; Haase, Ashley T; Li, Qingsheng

    2015-01-01

    HIV-1 depletes CD4+ T cells in the blood, lymphatic tissues, gut and lungs. Here we investigated the relationship between depletion and infection of CD4+ T cells in the lung parenchyma. The lungs of 38 Indian rhesus macaques in early to later stages of SIVmac251 infection were examined, and the numbers of CD4+ T cells and macrophages plus the frequency of SIV RNA+ cells were quantified. We showed that SIV infected macrophages in the lung parenchyma, but only in small numbers except in the setting of interstitial inflammation where large numbers of SIV RNA+ macrophages were detected. However, even in this setting, the number of macrophages was not decreased. By contrast, there were few infected CD4+ T cells in lung parenchyma, but CD4+ T cells were nonetheless depleted by unknown mechanisms. The CD4+ T cells in lung parenchyma were depleted even though they were not productively infected, whereas SIV can infect large numbers of macrophages in the setting of interstitial inflammation without depleting them. These observations point to the need for future investigations into mechanisms of CD4+ T cell depletion at this mucosal site, and into mechanisms by which macrophage populations are maintained despite high levels of infection. The large numbers of SIV RNA+ macrophages in lungs in the setting of interstitial inflammation indicates that lung macrophages can be an important source for SIV persistent infection.

  9. SIV Infection of Lung Macrophages.

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    Yue Li

    Full Text Available HIV-1 depletes CD4+ T cells in the blood, lymphatic tissues, gut and lungs. Here we investigated the relationship between depletion and infection of CD4+ T cells in the lung parenchyma. The lungs of 38 Indian rhesus macaques in early to later stages of SIVmac251 infection were examined, and the numbers of CD4+ T cells and macrophages plus the frequency of SIV RNA+ cells were quantified. We showed that SIV infected macrophages in the lung parenchyma, but only in small numbers except in the setting of interstitial inflammation where large numbers of SIV RNA+ macrophages were detected. However, even in this setting, the number of macrophages was not decreased. By contrast, there were few infected CD4+ T cells in lung parenchyma, but CD4+ T cells were nonetheless depleted by unknown mechanisms. The CD4+ T cells in lung parenchyma were depleted even though they were not productively infected, whereas SIV can infect large numbers of macrophages in the setting of interstitial inflammation without depleting them. These observations point to the need for future investigations into mechanisms of CD4+ T cell depletion at this mucosal site, and into mechanisms by which macrophage populations are maintained despite high levels of infection. The large numbers of SIV RNA+ macrophages in lungs in the setting of interstitial inflammation indicates that lung macrophages can be an important source for SIV persistent infection.

  10. The Secretion of IL-22 from Mucosal NKp44+ NK Cells Is Associated with Microbial Translocation and Virus Infection in SIV/SHIV-Infected Chinese Macaques

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    Wei Wang

    2014-01-01

    Full Text Available Microbial translocation (MT causes systemic immune activation in chronic human immunodeficiency virus (HIV infection. The role of a novel subtype of innate lymphoid cells, the NKp44+ NK cells, in HIV/simian immunodeficiency virus- (SIV- induced MT remains unknown. In this study, 12 simian-human immunodeficiency virus- (SHIV- infected macaques were chosen and split into two groups based on the MT level. Blood and Peripheral lymphoid tissue were sampled for flow cytometric analysis, viral load detection, and interleukin testing. Then, six naive Chinese macaques were used to determine the dynamics of cytokine secretion from mucosal NKp44+ NK cells in different phases of SIV infection. As a result, the degranulation capacity and IL-22 production of mucosal NKp44+ NK cells were associated with the MT level in the SHIV-infected macaques. And the number of mucosal NKp44+ NK cells and IL-22 secretion by these cells were lower in the chronic phase than in the early acute phase of SIV infection. The number of mucosal NKp44+ NK cells and interleukin-22 (IL-22 secretion by these cells increased before MT occurred. Therefore, we conclude that a decline in IL-22 production from mucosal NKp44+ NK cells induced by virus infection may be one of the causes of microbial translocation in HIV/SIV infection.

  11. Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load.

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    Collin R Diedrich

    2010-03-01

    Full Text Available HIV-infected individuals with latent Mycobacterium tuberculosis (Mtb infection are at significantly greater risk of reactivation tuberculosis (TB than HIV-negative individuals with latent TB, even while CD4 T cell numbers are well preserved. Factors underlying high rates of reactivation are poorly understood and investigative tools are limited. We used cynomolgus macaques with latent TB co-infected with SIVmac251 to develop the first animal model of reactivated TB in HIV-infected humans to better explore these factors. All latent animals developed reactivated TB following SIV infection, with a variable time to reactivation (up to 11 months post-SIV. Reactivation was independent of virus load but correlated with depletion of peripheral T cells during acute SIV infection. Animals experiencing reactivation early after SIV infection (<17 weeks had fewer CD4 T cells in the periphery and airways than animals reactivating in later phases of SIV infection. Co-infected animals had fewer T cells in involved lungs than SIV-negative animals with active TB despite similar T cell numbers in draining lymph nodes. Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active disease process. These results suggest initial T cell depletion may strongly influence outcomes of HIV-Mtb co-infection.

  12. The integration hypothesis: An evolutionary pathway to benign SIV infection.

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    Müller, V.; Boer, R.J. de

    Untreated human immunodeficiency virus (HIV) infection in humans is typically characterised by persistent high virus load, failure of the immune response to clear the virus, and fatal disease outcome. Natural hosts of closely related simian immunodeficiency viruses (SIVs)—e.g., sooty mangabeys

  13. SIV Infection Facilitates Mycobacterium tuberculosis Infection of Rhesus Macaques

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    Guo, Ming; Xian, Qiao-Yang; Rao, Yan; Zhang, Jing; Wang, Yong; Huang, Zhi-Xiang; Wang, Xin; Bao, Rong; Zhou, Li; Liu, Jin-Biao; Tang, Zhi-Jiao; Guo, De-yin; Qin, Chuan; Li, Jie-Liang; Ho, Wen-Zhe

    2017-01-01

    Tuberculosis (TB) is a common opportunistic infection and the leading cause of death for human immunodeficiency virus (HIV)-infected patients. Thus, it is necessary to understand the pathogenetic interactions between M.tb and HIV infection. In this study, we examined M.tb and/or simian immunodeficiency virus (SIV) infection of Chinese rhesus macaques. While there was little evidence that M.tb enhanced SIV infection of macaques, SIV could facilitate M.tb infection as demonstrated by X-rays, pathological and microbiological findings. Chest X-rays showed that co-infected animals had disseminated lesions in both left and right lungs, while M.tb mono-infected animals displayed the lesions only in right lungs. Necropsy of co-infected animals revealed a disseminated M.tb infection not only in the lungs but also in the extrapulmonary organs including spleen, pancreas, liver, kidney, and heart. The bacterial counts in the lungs, the bronchial lymph nodes, and the extrapulmonary organs of co-infected animals were significantly higher than those of M.tb mono-infected animals. The mechanistic studies demonstrated that two of three co-infected animals had lower levels of M.tb specific IFN-γ and IL-22 in PBMCs than M.tb mono-infected animals. These findings suggest that Chinese rhesus macaque is a suitable and alternative non-human primate model for SIV/M.tb coinfection studies. The impairment of the specific anti-TB immunity is likely to be a contributor of SIV-mediated enhancement M.tb infection. PMID:28133458

  14. CTL Escape and Viral Fitness in HIV/SIV Infection.

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    Seki, Sayuri; Matano, Tetsuro

    2011-01-01

    Cytotoxic T lymphocyte (CTL) responses exert a suppressive effect on HIV and simian immunodeficiency virus (SIV) replication. Under the CTL pressure, viral CTL escape mutations are frequently selected with viral fitness costs. Viruses with such CTL escape mutations often need additional viral genome mutations for recovery of viral fitness. Persistent HIV/SIV infection sometimes shows replacement of a CTL escape mutation with an alternative escape mutation toward higher viral fitness. Thus, multiple viral genome changes under CTL pressure are observed in the chronic phase of HIV/SIV infection. HIV/SIV transmission to HLA/MHC-mismatched hosts drives further viral genome changes including additional CTL escape mutations and reversions under different CTL pressure. Understanding of viral structure/function and host CTL responses would contribute to prediction of HIV evolution and control of HIV prevalence.

  15. Rhesus macaque IFITM3 gene polymorphisms and SIV infection.

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    Michael Winkler

    Full Text Available Interferon-induced transmembrane proteins (IFITMs have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV and human immunodeficiency virus (HIV infection, respectively. Rhesus macaques (Macaca mulatta are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV is one of the best models for HIV/AIDS in humans. However, information on the role of IFITM3 in SIV infection of rhesus macaques is currently lacking. We show that rhesus macaque (rh IFITM3 inhibits SIV and FLUAV entry in cell culture, although with moderately reduced efficiency as compared to its human counterpart. We further report the identification of 16 polymorphisms in the rhIFITM3 gene, three of which were exonic and synonymous while the remainder was located in non-coding regions. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. In cohort 1, several intronic polymorphisms were significantly associated with virus load or survival. However, an association with both parameters was not observed and significance was lost in most cases when animals were stratified for the presence of MHC allele Mamu-A1*001. Moreover, no significant genotype-phenotype associations were detected in cohort 2. These results suggest that, although IFITM3 can inhibit SIV infection in cell culture, genetic variation in rhIFITM3 might have only a minor impact on the course of SIV infection in experimentally infected animals.

  16. The secretion of IL-22 from mucosal NKp44⁺ NK cells is associated with microbial translocation and virus infection in SIV/SHIV-infected Chinese macaques.

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    Wang, Wei; Wu, Fangxin; Cong, Zhe; Liu, Kejian; Qin, Chuan; Wei, Qiang

    2014-01-01

    Microbial translocation (MT) causes systemic immune activation in chronic human immunodeficiency virus (HIV) infection. The role of a novel subtype of innate lymphoid cells, the NKp44(+) NK cells, in HIV/simian immunodeficiency virus- (SIV-) induced MT remains unknown. In this study, 12 simian-human immunodeficiency virus- (SHIV-) infected macaques were chosen and split into two groups based on the MT level. Blood and Peripheral lymphoid tissue were sampled for flow cytometric analysis, viral load detection, and interleukin testing. Then, six naive Chinese macaques were used to determine the dynamics of cytokine secretion from mucosal NKp44(+) NK cells in different phases of SIV infection. As a result, the degranulation capacity and IL-22 production of mucosal NKp44(+) NK cells were associated with the MT level in the SHIV-infected macaques. And the number of mucosal NKp44(+) NK cells and IL-22 secretion by these cells were lower in the chronic phase than in the early acute phase of SIV infection. The number of mucosal NKp44(+) NK cells and interleukin-22 (IL-22) secretion by these cells increased before MT occurred. Therefore, we conclude that a decline in IL-22 production from mucosal NKp44(+) NK cells induced by virus infection may be one of the causes of microbial translocation in HIV/SIV infection.

  17. An attenuated Lassa vaccine in SIV-infected rhesus macaques does not persist or cause arenavirus disease but does elicit Lassa virus-specific immunity.

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    Zapata, Juan C; Poonia, Bhawna; Bryant, Joseph; Davis, Harry; Ateh, Eugene; George, Lanea; Crasta, Oswald; Zhang, Yan; Slezak, Tom; Jaing, Crystal; Pauza, C David; Goicochea, Marco; Moshkoff, Dmitry; Lukashevich, Igor S; Salvato, Maria S

    2013-02-12

    Lassa hemorrhagic fever (LHF) is a rodent-borne viral disease that can be fatal for human beings. In this study, an attenuated Lassa vaccine candidate, ML29, was tested in SIV-infected rhesus macaques for its ability to elicit immune responses without instigating signs pathognomonic for arenavirus disease. ML29 is a reassortant between Lassa and Mopeia viruses that causes a transient infection in non-human primates and confers sterilizing protection from lethal Lassa viral challenge. However, since the LHF endemic area of West Africa also has high HIV seroprevalence, it is important to determine whether vaccination could be safe in the context of HIV infection. SIV-infected and uninfected rhesus macaques were vaccinated with the ML29 virus and monitored for specific humoral and cellular immune responses, as well as for classical and non-classical signs of arenavirus disease. Classical disease signs included viremia, rash, respiratory distress, malaise, high liver enzyme levels, and virus invasion of the central nervous system. Non-classical signs, derived from profiling the blood transcriptome of virulent and non-virulent arenavirus infections, included increased expression of interferon-stimulated genes (ISG) and decreased expression of COX2, IL-1β, coagulation intermediates and nuclear receptors needed for stress signaling. All vaccinated monkeys showed ML29-specific antibody responses and ML29-specific cell-mediated immunity. SIV-infected and uninfected rhesus macaques responded similarly to ML29 vaccination, and none developed chronic arenavirus infection. Importantly, none of the macaques developed signs, classical or non-classical, of arenavirus disease.

  18. Supplementary Material for: Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia

    2016-01-01

    Abstract Background Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. Results We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Conclusions Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

  19. Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia A.

    2016-04-23

    Background Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. Results We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Conclusions Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

  20. Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets.

    Science.gov (United States)

    Najera, Julia A; Bustamante, Eduardo A; Bortell, Nikki; Morsey, Brenda; Fox, Howard S; Ravasi, Timothy; Marcondes, Maria Cecilia Garibaldi

    2016-04-23

    Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

  1. Attenuation of pathogenic immune responses during infection with human and simian immunodeficiency virus (HIV/SIV by the tetracycline derivative minocycline.

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    Julia L Drewes

    Full Text Available HIV immune pathogenesis is postulated to involve two major mechanisms: 1 chronic innate immune responses that drive T cell activation and apoptosis and 2 induction of immune regulators that suppress T cell function and proliferation. Both arms are elevated chronically in lymphoid tissues of non-natural hosts, which ultimately develop AIDS. However, these mechanisms are not elevated chronically in natural hosts of SIV infection that avert immune pathogenesis despite similarly high viral loads. In this study we investigated whether minocycline could modulate these pathogenic antiviral responses in non-natural hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of type I interferon (IFN and the IFN-stimulated genes indoleamine 2,3-dioxygenase (IDO1 and TNF-related apoptosis inducing ligand (TRAIL in human plasmacytoid dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious influenza virus. Activation-induced TRAIL and expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4 in isolated CD4+ T cells were also reduced by minocycline. Translation of these in vitro findings to in vivo effects, however, were mixed as minocycline significantly reduced markers of activation and activation-induced cell death (CD25, Fas, caspase-3 but did not affect expression of IFNβ or the IFN-stimulated genes IDO1, FasL, or Mx in the spleens of chronically SIV-infected pigtailed macaques. TRAIL expression, reflecting the mixed effects of minocycline on activation and type I IFN stimuli, was reduced by half, but this change was not significant. These results show that minocycline administered after infection may protect against aspects of activation-induced cell death during HIV/SIV immune disease, but that in vitro effects of minocycline on type I IFN responses are not recapitulated in a rapid progressor model in vivo.

  2. Attenuation of Pathogenic Immune Responses during Infection with Human and Simian Immunodeficiency Virus (HIV/SIV) by the Tetracycline Derivative Minocycline

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    Drewes, Julia L.; Szeto, Gregory L.; Engle, Elizabeth L.; Liao, Zhaohao; Shearer, Gene M.; Zink, M. Christine; Graham, David R.

    2014-01-01

    HIV immune pathogenesis is postulated to involve two major mechanisms: 1) chronic innate immune responses that drive T cell activation and apoptosis and 2) induction of immune regulators that suppress T cell function and proliferation. Both arms are elevated chronically in lymphoid tissues of non-natural hosts, which ultimately develop AIDS. However, these mechanisms are not elevated chronically in natural hosts of SIV infection that avert immune pathogenesis despite similarly high viral loads. In this study we investigated whether minocycline could modulate these pathogenic antiviral responses in non-natural hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of type I interferon (IFN) and the IFN-stimulated genes indoleamine 2,3-dioxygenase (IDO1) and TNF-related apoptosis inducing ligand (TRAIL) in human plasmacytoid dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious influenza virus. Activation-induced TRAIL and expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in isolated CD4+ T cells were also reduced by minocycline. Translation of these in vitro findings to in vivo effects, however, were mixed as minocycline significantly reduced markers of activation and activation-induced cell death (CD25, Fas, caspase-3) but did not affect expression of IFNβ or the IFN-stimulated genes IDO1, FasL, or Mx in the spleens of chronically SIV-infected pigtailed macaques. TRAIL expression, reflecting the mixed effects of minocycline on activation and type I IFN stimuli, was reduced by half, but this change was not significant. These results show that minocycline administered after infection may protect against aspects of activation-induced cell death during HIV/SIV immune disease, but that in vitro effects of minocycline on type I IFN responses are not recapitulated in a rapid progressor model in vivo. PMID:24732038

  3. Partial protection of SIV-infected rhesus monkeys against superinfection with a heterologous SIV isolate

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    Korber, Bette [Los Alamos National Laboratory

    2009-01-01

    Although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (HIV-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infection and the biologic consequences of superinfection are not well understood. We explored these questions in the simian immunodeficiency virus (SIV)/rhesus monkey model of HIV-1/AIDS. We infected cohorts of rhesus monkeys with either SIVmac251 or SIVsmE660 and then exposed animals to the reciprocal virus through intrarectal inoculations. Employing a quantitative real-time PCR assay, we determined the replication kinetics of the two strains of virus for 20 weeks. We found that primary infection with a replication-competent virus did not protect against acquisition of infection by a heterologous virus but did confer relative control of the superinfecting virus. In animals that became superinfected, there was a reduction in peak replication and rapid control of the second virus. The relative susceptibility to superinfection was not correlated with CD4(+) T-cell count, CD4(+) memory T-cell subsets, cytokine production by virus-specific CD8(+) or CD4(+) cells, or neutralizing antibodies at the time of exposure to the second virus. Although there were transient increases in viral loads of the primary virus and a modest decline in CD4(+) T-cell counts after superinfection, there was no evidence of disease acceleration. These findings indicate that an immunodeficiency virus infection confers partial protection against a second immunodeficiency virus infection, but this protection may be mediated by mechanisms other than classical adaptive immune responses.

  4. Stable multi-infection of splenocytes during SIV infection - the basis for continuous recombination

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    Schultz Anke

    2012-04-01

    Full Text Available Abstract Background Recombination is an important mechanism in the generation of genetic diversity of the human (HIV and simian (SIV immunodeficiency viruses. It requires the co-packaging of divergent RNA genomes into the same retroviral capsid and subsequent template switching during the reverse transcription reaction. By HIV-specific fluorescence in situ hybridization (FISH, we have previously shown that the splenocytes from 2 chronically infected patients with Castelman's disease were multi-infected and thus fulfill the in vivo requirements to generate genetic diversity by recombination. In order to analyze when multi-infection first occurs during a lentivirus infection and how the distribution of multi-infection evolves during the disease course, we now determined the SIV copy numbers from splenocytes of 11 SIVmac251-infected rhesus macaques cross-sectionally covering the time span of primary infection throughout to end-stage immunodeficiency. Results SIV multi-infection of single splenocytes was readily detected in all monkeys and all stages of the infection. Single-infected cells were more frequent than double- or triple- infected cells. There was no strong trend linking the copy number distribution to plasma viral load, disease stage, or CD4 cell counts. Conclusions SIV multi-infection of single cells is already established during the primary infection phase thus enabling recombination to affect viral evolution in vivo throughout the disease course.

  5. Immunogenicity of viral vector, prime-boost SIV vaccine regimens in infant rhesus macaques: attenuated vesicular stomatitis virus (VSV) and modified vaccinia Ankara (MVA) recombinant SIV vaccines compared to live-attenuated SIV.

    Science.gov (United States)

    Van Rompay, Koen K A; Abel, Kristina; Earl, Patricia; Kozlowski, Pamela A; Easlick, Juliet; Moore, Joseph; Buonocore-Buzzelli, Linda; Schmidt, Kimberli A; Wilson, Robert L; Simon, Ian; Moss, Bernard; Rose, Nina; Rose, John; Marthas, Marta L

    2010-02-10

    In a previously developed infant macaque model mimicking HIV infection by breast-feeding, we demonstrated that intramuscular immunization with recombinant poxvirus vaccines expressing simian immunodeficiency virus (SIV) structural proteins provided partial protection against infection following oral inoculation with virulent SIV. In an attempt to further increase systemic but also local antiviral immune responses at the site of viral entry, we tested the immunogenicity of different orally administered, replicating vaccines. One group of newborn macaques received an oral prime immunization with a recombinant vesicular stomatitis virus expressing SIVmac239 gag, pol and env (VSV-SIVgpe), followed 2 weeks later by an intramuscular boost immunization with MVA-SIV. Another group received two immunizations with live-attenuated SIVmac1A11, administered each time both orally and intravenously. Control animals received mock immunizations or non-SIV VSV and MVA control vectors. Analysis of SIV-specific immune responses in blood and lymphoid tissues at 4 weeks of age demonstrated that both vaccine regimens induced systemic antibody responses and both systemic and local cell-mediated immune responses. The safety and immunogenicity of the VSV-SIVgpe+MVA-SIV immunization regimen described in this report provide the scientific incentive to explore the efficacy of this vaccine regimen against virulent SIV exposure in the infant macaque model. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  6. Influence of naturally occurring simian foamy viruses (SFVs) on SIV disease progression in the rhesus macaque (Macaca mulatta) model.

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    Choudhary, Anil; Galvin, Teresa A; Williams, Dhanya K; Beren, Joel; Bryant, Mark A; Khan, Arifa S

    2013-06-06

    We have investigated the influence of naturally occurring simian foamy viruses (SFVs) on simian immunodeficiency virus (SIV) infection and disease in Indian rhesus macaques. Animals were divided into two groups based upon presence or absence of SFV; in each group, eight monkeys were injected with SIV(mac239) virus obtained from a molecular clone and four were injected with medium. Blood was collected every two weeks for evaluation of SIV infection based upon T cell-subsets, plasma viral load, development and persistence of virus-specific antibodies, and clinical changes by physical examination and hematology. Comparative analysis of SFV+/SIV+ and SFV-/SIV+ monkey groups indicated statistically significant differences in the plasma viral load between 6-28 weeks, particularly after reaching plateau at 20-28 weeks, in the CD4+ and CD8+ T-cell numbers over the entire study period (2-43 weeks), and in the survival rates evaluated at 49 weeks. There was an increase in the plasma viral load, a decreasing trend in the CD4+ T cells, and a greater number of animal deaths in the SFV+/SIV+ group. The results, although based upon a small number of animals, indicated that pre-existing SFV infection can influence SIV infection and disease outcome in the rhesus macaque model. The study highlights consideration of the SFV status in evaluating results from SIV pathogenesis and vaccine challenge studies in monkeys and indicates the potential use of the SFV/SIV monkey model to study the dynamics of SFV and HIV-1 dual infections, recently reported in humans.

  7. Influence of Naturally Occurring Simian Foamy Viruses (SFVs on SIV Disease Progression in the Rhesus Macaque (Macaca mulatta Model

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    Joel Beren

    2013-06-01

    Full Text Available We have investigated the influence of naturally occurring simian foamy viruses (SFVs on simian immunodeficiency virus (SIV infection and disease in Indian rhesus macaques. Animals were divided into two groups based upon presence or absence of SFV; in each group, eight monkeys were injected with SIVmac239 virus obtained from a molecular clone and four were injected with medium. Blood was collected every two weeks for evaluation of SIV infection based upon T cell-subsets, plasma viral load, development and persistence of virus-specific antibodies, and clinical changes by physical examination and hematology. Comparative analysis of SFV+/SIV+ and SFV−/SIV+ monkey groups indicated statistically significant differences in the plasma viral load between 6–28 weeks, particularly after reaching plateau at 20–28 weeks, in the CD4+ and CD8+ T-cell numbers over the entire study period (2–43 weeks, and in the survival rates evaluated at 49 weeks. There was an increase in the plasma viral load, a decreasing trend in the CD4+ T cells, and a greater number of animal deaths in the SFV+/SIV+ group. The results, although based upon a small number of animals, indicated that pre-existing SFV infection can influence SIV infection and disease outcome in the rhesus macaque model. The study highlights consideration of the SFV status in evaluating results from SIV pathogenesis and vaccine challenge studies in monkeys and indicates the potential use of the SFV/SIV monkey model to study the dynamics of SFV and HIV-1 dual infections, recently reported in humans.

  8. Nef gene evolution from a single transmitted strain in acute SIV infection

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    Bimber Benjamin N

    2009-06-01

    Full Text Available Abstract Background The acute phase of immunodeficiency virus infection plays a crucial role in determining steady-state virus load and subsequent progression of disease in both humans and nonhuman primates. The acute period is also the time when vaccine-mediated effects on host immunity are likely to exert their major effects on virus infection. Recently we developed a Monte-Carlo (MC simulation with mathematical analysis of viral evolution during primary HIV-1 infection that enables classification of new HIV-1 infections originating from multiple versus single transmitted viral strains and the estimation of time elapsed following infection. Results A total of 322 SIV nef SIV sequences, collected during the first 3 weeks following experimental infection of two rhesus macaques with the SIVmac239 clone, were analyzed and found to display a comparable level of genetic diversity, 0.015% to 0.052%, with that of env sequences from acute HIV-1 infection, 0.005% to 0.127%. We confirmed that the acute HIV-1 infection model correctly identified the experimental SIV infections in rhesus macaques as "homogenous" infections, initiated by a single founder strain. The consensus sequence of the sampled strains corresponded to the transmitted sequence as the model predicted. However, measured sequential decrease in diversity at day 7, 11, and 18 post infection violated the model assumption, neutral evolution without any selection. Conclusion While nef gene evolution over the first 3 weeks of SIV infection originating from a single transmitted strain showed a comparable rate of sequence evolution to that observed during acute HIV-1 infection, a purifying selection for the founder nef gene was observed during the early phase of experimental infection of a nonhuman primate.

  9. Low dose rectal inoculation of rhesus macaques by SIV SME660 or SIV MAC251 recapitulates human mucosal infection by HIV-1

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    Koraber, Bette [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory; Hraber, Peter [Los Alamos National Laboratory; Giorgi, E [Los Alamos National Laboratory; Bhattacharya, T [Los Alamos National Laboratory

    2009-01-01

    Recently, we developed a novel approach to the identification of transmitted or early founder HIV -1 genomes in acutely infected humans based on single genome amplification and sequencing. Here we tested this approach in 18 acutely infected Indian rhesus macaques to determine the molecular features of SIV transmission. Animals were inoculated intrarectally (IR) or intravenously (IV) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV -1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA one to five weeks after infection. IR inoculation was followed by productive infection by one or few viruses (median 1; range 1-5) that diversified randomly with near star-like phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or few nuc1eotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder virus( es). IV infection was approximately 10,000-fold more efficient than IR infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV -1.

  10. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

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    W L William Chang

    Full Text Available Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease.

  11. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

    Science.gov (United States)

    Chang, W L William; Gonzalez, Denise F; Kieu, Hung T; Castillo, Luis D; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D; Shacklett, Barbara L; Barry, Peter A; Sparger, Ellen E

    2017-01-01

    Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease.

  12. Immunological alterations and associated diseases in mandrills (Mandrillus sphinx) naturally co-infected with SIV and STLV.

    Science.gov (United States)

    Souquière, Sandrine; Makuwa, Maria; Sallé, Bettina; Lepelletier, Yves; Mortreux, Franck; Hermine, Olivier; Kazanji, Mirdad

    2014-04-01

    Mandrills are naturally infected with simian T-cell leukaemia virus type 1 (STLV-1) and simian immunodeficiency virus (SIV)mnd. In humans, dual infection with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type 1 (HTLV-1) may worsen their clinical outcome. We evaluated the effect of co-infection in mandrills on viral burden, changes in T-cell subsets and clinical outcome. The SIV viral load was higher in SIV-infected mandrills than in co-infected animals, whereas the STLV-1 proviral load was higher in co-infected than in mono-infected groups. Dually infected mandrills had a statistically significantly lower CD4+ T-cell count, a lower proportion of naive CD8+ T cells and a higher proportion of central memory cells. CD4(+) and CD8(+) T cells from SIV-infected animals had a lower percentage of Ki67 than those from the other groups. Co-infected monkeys had higher percentages of activated CD4(+) and CD8(+) T cells. Two co-infected mandrills with high immune activation and clonal integration of STLV provirus showed pathological manifestations (infective dermatitis and generalised scabies) rarely encountered in nonhuman primates. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. A limited number of simian immunodeficiency virus (SIV) env variants are transmitted to rhesus macaques vaginally inoculated with SIVmac251.

    Science.gov (United States)

    Stone, Mars; Keele, Brandon F; Ma, Zhong-Min; Bailes, Elizabeth; Dutra, Joseph; Hahn, Beatrice H; Shaw, George M; Miller, Christopher J

    2010-07-01

    Single-genome amplification (SGA) and sequencing of HIV-1 RNA in plasma of acutely infected humans allows the identification and enumeration of transmitted/founder viruses responsible for productive systemic infection. Use of this strategy as a means for identifying transmitted viruses suggested that intrarectal simian immunodeficiency virus (SIV) inoculation of macaques recapitulates key features of human rectal infection. However, no studies have used the SGA strategy to identify vaginally transmitted virus(es) in macaques or to determine how early SIV diversification in vaginally infected animals compares with HIV-1 in humans. We used SGA to amplify 227 partial env sequences from a SIVmac251 challenge stock and from seven rhesus macaques at the earliest plasma viral RNA-positive time point after low- and high-dose intravaginal inoculation. Sequences were analyzed phylogenetically to determine the relationship of transmitted/founder viruses within and between each animal and the challenge stock. In each animal, discrete low-diversity env sequence lineages were evident, and these coalesced phylogenetically to identical or near-identical env sequences in the challenge stock, thus confirming the validity of the SGA sequencing and modeling strategy for identifying vaginally transmitted SIV. Between 1 and 10 viruses were responsible for systemic infection, similar to humans infected by sexual contact, and the set of viruses transmitted to the seven animals studied represented the full genetic constellation of the challenge stock. These findings recapitulate many of the features of sexual HIV-1 transmission in women. Furthermore, the SIV rhesus macaque model can be used to understand the factors that influence the transmission of single versus multiple SIV variants.

  14. Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection

    DEFF Research Database (Denmark)

    Muenchhoff, Maximilian; Adland, Emily; Karimanzira, Owen

    2016-01-01

    preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-naïve children aged >5 years maintaining normal-for-Age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26......Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors......,000 copies/ml). Potent, broadly neutralizing antibody responses in most of the subjects and strong virus-specific T cell activity were present but did not drive pediatric nonprogression. However, reduced CCR5 expression and low HIV infection in long-lived central memory CD4 T cells were observed in pediatric...

  15. Control of viremia and prevention of AIDS following immunotherapy of SIV-infected macaques with peptide-pulsed blood.

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    Robert De Rose

    2008-05-01

    Full Text Available Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIV(mac251 replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably approximately 10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans.

  16. Quantifying transmission by stage of infection in the field: the example of SIV-1 and STLV-1 infecting mandrills.

    Science.gov (United States)

    Roussel, Marion; Pontier, Dominique; Kazanji, Mirdad; Ngoubangoye, Barthélémy; Mahieux, Renaud; Verrier, Delphine; Fouchet, David

    2015-03-01

    The early stage of viral infection is often followed by an important increase of viral load and is generally considered to be the most at risk for pathogen transmission. Most methods quantifying the relative importance of the different stages of infection were developed for studies aimed at measuring HIV transmission in Humans. However, they cannot be transposed to animal populations in which less information is available. Here we propose a general method to quantify the importance of the early and late stages of the infection on micro-organism transmission from field studies. The method is based on a state space dynamical model parameterized using Bayesian inference. It is illustrated by a 28 years dataset in mandrills infected by Simian Immunodeficiency Virus type-1 (SIV-1) and the Simian T-Cell Lymphotropic Virus type-1 (STLV-1). For both viruses we show that transmission is predominant during the early stage of the infection (transmission ratio for SIV-1: 1.16 [0.0009; 18.15] and 9.92 [0.03; 83.8] for STLV-1). However, in terms of basic reproductive number (R0 ), which quantifies the weight of both stages in the spread of the virus, the results suggest that the epidemics of SIV-1 and STLV-1 are mainly driven by late transmissions in this population. © 2014 Wiley Periodicals, Inc.

  17. Collapse of Cytolytic Potential in SIV-Specific CD8+ T Cells Following Acute SIV Infection in Rhesus Macaques.

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    Emily R Roberts

    2016-12-01

    Full Text Available Poor maintenance of cytotoxic factor expression among HIV-specific CD8+ T cells, in part caused by dysregulated expression of the transcription factor T-bet, is associated with HIV disease progression. However, the precise evolution and context in which CD8+ T cell cytotoxic functions become dysregulated in HIV infection remain unclear. Using the rhesus macaque (RM SIV infection model, we evaluated the kinetics of SIV-specific CD8+ T cell cytolytic factor expression in peripheral blood, lymph node, spleen, and gut mucosa from early acute infection through chronic infection. We identified rapid acquisition of perforin and granzyme B expression in SIV-specific CD8+ T cells in blood, secondary lymphoid tissues and gut mucosa that collapsed rapidly during the transition to chronic infection. The evolution of this expression profile was linked to low expression of T-bet and occurred independent of epitope specificity, viral escape patterns and tissue origin. Importantly, during acute infection SIV-specific CD8+ T cells that maintained T-bet expression retained the ability to express granzyme B after stimulation, but this relationship was lost in chronic infection. Together, these data demonstrate the loss of cytolytic machinery in SIV-specific CD8+ T cells in blood and at tissue sites of viral reservoir and active replication during the transition from acute to chronic infection. This phenomenon occurs despite persistent high levels of viremia suggesting that an inability to maintain properly regulated cytotoxic T cell responses in all tissue sites enables HIV/SIV to avoid immune clearance, establish persistent viral reservoirs in lymphoid tissues and gut mucosa, and lead ultimately to immunopathogenesis and death.

  18. Collapse of Cytolytic Potential in SIV-Specific CD8+ T Cells Following Acute SIV Infection in Rhesus Macaques.

    Science.gov (United States)

    Roberts, Emily R; Carnathan, Diane G; Li, Hui; Shaw, George M; Silvestri, Guido; Betts, Michael R

    2016-12-01

    Poor maintenance of cytotoxic factor expression among HIV-specific CD8+ T cells, in part caused by dysregulated expression of the transcription factor T-bet, is associated with HIV disease progression. However, the precise evolution and context in which CD8+ T cell cytotoxic functions become dysregulated in HIV infection remain unclear. Using the rhesus macaque (RM) SIV infection model, we evaluated the kinetics of SIV-specific CD8+ T cell cytolytic factor expression in peripheral blood, lymph node, spleen, and gut mucosa from early acute infection through chronic infection. We identified rapid acquisition of perforin and granzyme B expression in SIV-specific CD8+ T cells in blood, secondary lymphoid tissues and gut mucosa that collapsed rapidly during the transition to chronic infection. The evolution of this expression profile was linked to low expression of T-bet and occurred independent of epitope specificity, viral escape patterns and tissue origin. Importantly, during acute infection SIV-specific CD8+ T cells that maintained T-bet expression retained the ability to express granzyme B after stimulation, but this relationship was lost in chronic infection. Together, these data demonstrate the loss of cytolytic machinery in SIV-specific CD8+ T cells in blood and at tissue sites of viral reservoir and active replication during the transition from acute to chronic infection. This phenomenon occurs despite persistent high levels of viremia suggesting that an inability to maintain properly regulated cytotoxic T cell responses in all tissue sites enables HIV/SIV to avoid immune clearance, establish persistent viral reservoirs in lymphoid tissues and gut mucosa, and lead ultimately to immunopathogenesis and death.

  19. Role of Monocyte/Macrophages during HIV/SIV Infection in Adult and Pediatric Acquired Immune Deficiency Syndrome

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    Kristen M. Merino

    2017-12-01

    Full Text Available Monocytes/macrophages are a diverse group of cells that act as first responders in innate immunity and then as mediators for adaptive immunity to help clear infections. In performing these functions, however, the macrophage inflammatory responses can also contribute to pathogenesis. Various monocyte and tissue macrophage subsets have been associated with inflammatory disorders and tissue pathogeneses such as occur during HIV infection. Non-human primate research of simian immunodeficiency virus (SIV has been invaluable in better understanding the pathogenesis of HIV infection. The question of HIV/SIV-infected macrophages serving as a viral reservoir has become significant for achieving a cure. In the rhesus macaque model, SIV-infected macrophages have been shown to promote pathogenesis in several tissues resulting in cardiovascular, metabolic, and neurological diseases. Results from human studies illustrated that alveolar macrophages could be an important HIV reservoir and humanized myeloid-only mice supported productive HIV infection and viral persistence in macrophages during ART treatment. Depletion of CD4+ T cells is considered the primary cause for terminal progression, but it was reported that increasing monocyte turnover was a significantly better predictor in SIV-infected adult macaques. Notably, pediatric cases of HIV/SIV exhibit faster and more severe disease progression than adults, yet neonates have fewer target T cells and generally lack the hallmark CD4+ T cell depletion typical of adult infections. Current data show that the baseline blood monocyte turnover rate was significantly higher in neonatal macaques compared to adults and this remained high with disease progression. In this review, we discuss recent data exploring the contribution of monocytes and macrophages to HIV/SIV infection and progression. Furthermore, we highlight the need to further investigate their role in pediatric cases of infection.

  20. Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques

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    Marx Preston

    2006-12-01

    Full Text Available Abstract Background Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1 is a major obstacle to successful antiretroviral therapy (ART in HIV-infected patients. Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can be explored in non-human primates infected with simian immunodeficiency virus (SIV. Rhesus macaques infected with live, attenuated SIV develop robust SIV-specific immune responses but remain viremic, often at low levels, for periods of months to years, thus providing a model in which to evaluate the contribution of antiviral immunity to drug efficacy. To investigate the extent to which SIV-specific immune responses augment suppression of drug-resistant SIV, rhesus macaques infected with live, attenuated SIVmac239Δnef were treated with the reverse transcriptase (RT inhibitor tenofovir, and then challenged with pathogenic SIVmac055, which has a five-fold reduced sensitivity to tenofovir. Results Replication of SIVmac055 was detected in untreated macaques infected with SIVmac239Δnef, and in tenofovir-treated, naïve control macaques. The majority of macaques infected with SIVmac055 experienced high levels of plasma viremia, rapid CD4+ T cell loss and clinical disease progression. By comparison, macaques infected with SIVmac239Δnef and treated with tenofovir showed no evidence of replicating SIVmac055 in plasma using allele-specific real-time PCR assays with a limit of sensitivity of 50 SIV RNA copies/ml plasma. These animals remained clinically healthy with stable CD4+ T cell counts during three years of follow-up. Both the tenofovir-treated and untreated macaques infected with SIVmac239Δnef had antibody responses to SIV gp130 and p27 antigens and SIV-specific CD8+ T cell responses prior to SIVmac055 challenge, but only those animals receiving concurrent treatment with tenofovir resisted infection with SIVmac055. Conclusion

  1. Inhibition of adaptive immune responses leads to a fatal clinical outcome in SIV-infected pigtailed macaques but not vervet African green monkeys.

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    Jörn E Schmitz

    2009-12-01

    Full Text Available African green monkeys (AGM and other natural hosts for simian immunodeficiency virus (SIV do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonnatural hosts, we used SIV(agmVer90 to infect vervet AGM and pigtailed macaques (PTM. This infection results in robust viral replication in both vervet AGM and pigtailed macaques (PTM but only induces AIDS in the latter species. We delayed the development of adaptive immune responses through combined administration of anti-CD8 and anti-CD20 lymphocyte-depleting antibodies during primary infection of PTM (n = 4 and AGM (n = 4, and compared these animals to historical controls infected with the same virus. Lymphocyte depletion resulted in a 1-log increase in primary viremia and a 4-log increase in post-acute viremia in PTM. Three of the four PTM had to be euthanized within 6 weeks of inoculation due to massive CMV reactivation and disease. In contrast, all four lymphocyte-depleted AGM remained healthy. The lymphocyte-depleted AGM showed only a trend toward a prolongation in peak viremia but the groups were indistinguishable during chronic infection. These data show that adaptive immune responses are critical for controlling disease progression in pathogenic SIV infection in PTM. However, the maintenance of a disease-free course of SIV infection in AGM likely depends on a number of mechanisms including non-adaptive immune mechanisms.

  2. Innate Lymphoid Cells in HIV/SIV Infections.

    Science.gov (United States)

    Shah, Spandan V; Manickam, Cordelia; Ram, Daniel R; Reeves, R Keith

    2017-01-01

    Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC) have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s) in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  3. Innate Lymphoid Cells in HIV/SIV Infections

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    Spandan V. Shah

    2017-12-01

    Full Text Available Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  4. Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection.

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    Sandrine Peruchon

    Full Text Available BACKGROUND: Primary HIV-infected patients display severe and irreversible damage to different blood B-cell subsets which is not restored by highly efficient anti-retroviral therapy (HAART. Because longitudinal investigations of primary HIV-infection is limited by the availability of lymphoid organs, we studied the tissue-specific B-cell dysfunctions in acutely simian immunodeficiency virus (SIV mac251-infected Cynomolgus macaques. METHODS AND FINDINGS: Experiments were performed on three groups of macaques infected for 14, 21 or 28 days and on three groups of animals treated with HAART for two-weeks either initiated at 4 h, 7 or 14 days post-infection (p.i.. We have simultaneously compared changes in B-cell phenotypes and functions and tissue organization of B-cell areas in various lymphoid organs. We showed that SIV induced a steady decline in SIgG-expressing memory (SIgD(-CD27(+ B-cells in spleen and lymph nodes during the first 4 weeks of infection, concomitant to selective homing/sequestration of B-cells to the small intestine and spleen. SIV non-specific Ig production was transiently increased before D14p.i., whereas SIV-specific Ig production was only detectable after D14p.i., coinciding with the presence of CD8(+ T-cells and IgG-expressing plasma cells within germinal centres. Transient B-cell apoptosis on D14p.i. and commitment to terminal differentiation contributed to memory B-cell loss. HAART abrogated B-cell apoptosis, homing to the small intestine and SIV-specific Ig production but had minimal effect on early Ig production, increased B-cell proportions in spleen and loss of memory B-cells. Therefore, virus-B-cell interactions and SIV-induced inflammatory cytokines may differently contribute to early B-cell dysfunction and impaired SIV/HIV-specific antibody response. CONCLUSIONS: These data establish tissue-specific impairments in B-cell trafficking and functions and a generalized and steady memory B-cell loss in secondary lymphoid

  5. Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection.

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    Glavan, T W; Gaulke, C A; Santos Rocha, C; Sankaran-Walters, S; Hirao, L A; Raffatellu, M; Jiang, G; Bäumler, A J; Goulart, L R; Dandekar, S

    2016-05-01

    HIV targets the gut mucosa early in infection, causing immune and epithelial barrier dysfunction and disease progression. However, gut mucosal sensing and innate immune signaling through mucosal pattern recognition receptors (PRRs) during HIV infection and disease progression are not well defined. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model of AIDS, we found a robust increase in PRRs and inflammatory cytokine gene expression during the acute SIV infection in both peripheral blood and gut mucosa, coinciding with viral replication. PRR expression remained elevated in peripheral blood following the transition to chronic SIV infection. In contrast, massive dampening of PRR expression was detected in the gut mucosa, despite the presence of detectable viral loads. Exceptionally, expression of Toll-like receptor 4 (TLR4) and TLR8 was downmodulated and diverged from expression patterns for most other TLRs in the gut. Decreased mucosal PRR expression was associated with increased abundance of several pathogenic bacterial taxa, including Pasteurellaceae members, Aggregatibacter and Actinobacillus, and Mycoplasmataceae family. Early antiretroviral therapy led to viral suppression but only partial maintenance of gut PRRs and cytokine gene expression. In summary, SIV infection dampens mucosal innate immunity through PRR dysregulation and may promote immune activation, gut microbiota changes, and ineffective viral clearance.

  6. Distal leucines are key functional determinants of Alix-binding simian immunodeficiency virus SIV(smE543) and SIV(mac239) type 3 L domains.

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    Bello, Nana F; Wu, Fan; Sette, Paola; Dussupt, Vincent; Hirsch, Vanessa M; Bouamr, Fadila

    2011-11-01

    In addition to PTAP L domains, primate lentiviruses carry Alix-binding motifs that include the recently described type 3 SREKPYKEVTEDLLHLNSLF sequence. We examined the requirements for the type 3 sequence motif in simian immunodeficiency virus SIV(smE543) and identified the (499)LNSLF(503) sequence as a key functional determinant. Mutation of distal leucines (499)L and (502)L (LL mutant) caused an inhibitory effect on Alix-dependent SIV(smE543) release that was quantitatively similar to that observed following disruption of the type 3 L domain or RNA interference (RNAi) depletion of Alix. Similar results were obtained with the SIV(mac239) LL mutant. Thus, distal leucines are key determinants of SIV(smE543) and SIV(mac239) type 3 L domains.

  7. Transcription Profiling Reveals Potential Mechanisms of Dysbiosis in the Oral Microbiome of Rhesus Macaques with Chronic Untreated SIV Infection

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    Ocon, Susan; Murphy, Christina; Dang, Angeline T.; Sankaran-Walters, Sumathi; Li, Chin-Shang; Tarara, Ross; Borujerdpur, Niku; Dandekar, Satya; Paster, Bruce J.; George, Michael D.

    2013-01-01

    A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and “macaque versions” of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides. PMID:24312248

  8. Role of the long cytoplasmic domain of the SIV Env glycoprotein in early and late stages of infection

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    Khaoustov Vladimir

    2007-12-01

    Full Text Available Abstract Background The Env glycoproteins of retroviruses play an important role in the initial steps of infection involving the binding to cell surface receptors and entry by membrane fusion. The Env glycoprotein also plays an important role in viral assembly at a late step of infection. Although the Env glycoprotein interacts with viral matrix proteins and cellular proteins associated with lipid rafts, its possible role during the early replication events remains unclear. Truncation of the cytoplasmic tail (CT of the Env glycoprotein is acquired by SIV in the course of adaptation to human cells, and is known to be a determinant of SIV pathogenicity. Results We compared SIV viruses with full length or truncated (T Env glycoproteins to analyze possible differences in entry and post-entry events, and assembly of virions. We observed that early steps in replication of SIV with full length or T Env were similar in dividing and non-dividing cells. However, the proviral DNA of the pathogenic virus clone SIVmac239 with full length Env was imported to the nucleus about 20-fold more efficiently than proviral DNA of SIVmac239T with T Env, and 100-fold more efficiently than an SIVmac18T variant with a single mutation A239T in the SU subunit and with a truncated cytoplasmic tail (CT. In contrast, proviral DNA of SIVmac18 with a full length CT and with a single mutation A239T in the SU subunit was imported to the nucleus about 50-fold more efficiently than SIVmac18T. SIV particles with full length Env were released from rhesus monkey PBMC, whereas a restriction of release of virus particles was observed from human 293T, CEMx174, HUT78 or macrophages. In contrast, SIV with T Envs were able to overcome the inhibition of release in human HUT78, CEMx174, 293T or growth-arrested CEMx174 cells and macrophages resulting in production of infectious particles. We found that the long CT of the Env glycoprotein was required for association of Env with lipid rafts. An

  9. Estimating the impact of vaccination in acute SHIV-SIV infection

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    Ribeiro, Ruy [Los Alamos National Laboratory

    2008-01-01

    Human Immunodeficiency Virus (HIV) infects approxmately 0.5% of the world population, and is a major cause of morbidity and mortality worldwide. A vaccine for HIV is urgently required, and a variety of vaccine modalities have been tested in animal models of infection. A number of these studies have shown protection in monkey models of infection, although the ability of the vaccine to protect appears to vary with the viral strain and animal model used. The recent failure of a large vaccine study in humans suggests that further understanding of the basic dynamics of infection and impact of vaccination are required, in order to understand the variable efficacy of vaccination in different infections. The dynamics of HIV infection have been studied in humans and in a variety of animal models. The standard model of infection has been used to estimate the basic reproductive ratio (R{sub 0}) of the virus, calculated from the growth rate of virus in acute infection. This method has not been useful in studying the effects of vaccination, since, in the vaccines developed so far, early growth rates of virus do not differ between control and vaccinated animals. Here, we use the standard model of viral dynamics to derive the reproductive ratio from the peak viral load and nadir of target cell numbers in acute infection. We apply this method to data from studies of vaccination in Simian Human Immunodeficiency Virus (SHIV) and Simian Immunodeficiency Virus (SIV) infection and demonstrate that vaccination can reduce the reproductive ratio by 2.3 and 2 fold respectively. This method allows the comparison of vaccination efficacy amongst different viral strains and animal models in vivo.

  10. Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

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    Joseph L Mankowski

    Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

  11. Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques

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    Ahsan, Muhammad H.; Gill, Amy F.; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S., E-mail: rveazey@tulane.edu

    2013-11-15

    Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected in acute infection and in AIDS with similar trends in blood monocytes. Significantly higher percentages of apoptotic (AC3+) Kupffer cells were also found in acute and AIDS stages. However, productively infected cells were not detected in liver of 41/42 animals examined, despite abundant infected cells in gut and lymph nodes of all animals. Increased rates of Kupffer cell proliferation resulting in an increase in Kupffer cells without productive infection indicate SIV infection affects Kupffer cells, but the liver does not appear to be a major site of productive viral replication. - Highlights: • Kupffer cells increase in the liver of SIV-infected macaques. • Increased proliferation and apoptosis of Kupffer cells occurs in SIV infection. • Productively infected cells are rarely detected in the liver. • The liver is not a major site for SIV replication.

  12. HIV/SIV infection primes monocytes and dendritic cells for apoptosis.

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    Mireille Laforge

    2011-06-01

    Full Text Available Subversion or exacerbation of antigen-presenting cells (APC death modulates host/pathogen equilibrium. We demonstrated during in vitro differentiation of monocyte-derived macrophages and monocyte-derived dendritic cells (DCs that HIV sensitizes the cells to undergo apoptosis in response to TRAIL and FasL, respectively. In addition, we found that HIV-1 increased the levels of pro-apoptotic Bax and Bak molecules and decreased the levels of anti-apoptotic Mcl-1 and FLIP proteins. To assess the relevance of these observations in the context of an experimental model of HIV infection, we investigated the death of APC during pathogenic SIV-infection in rhesus macaques (RMs. We demonstrated increased apoptosis, during the acute phase, of both peripheral blood DCs and monocytes (CD14(+ from SIV(+RMs, associated with a dysregulation in the balance of pro- and anti-apoptotic molecules. Caspase-inhibitor and death receptors antagonists prevented apoptosis of APCs from SIV(+RMs. Furthermore, increased levels of FasL in the sera of pathogenic SIV(+RMs were detected, compared to non-pathogenic SIV infection of African green monkey. We suggest that inappropriate apoptosis of antigen-presenting cells may contribute to dysregulation of cellular immunity early in the process of HIV/SIV infection.

  13. Characterization of SIV in the Oral Cavity and in Vitro Inhibition of SIV by Rhesus Macaque Saliva

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    Thomas, Jessica S.; Lacour, Nedra; Kozlowski, Pamela A.; Nelson, Steve; Bagby, Gregory J.

    2010-01-01

    Abstract Human immunodeficiency virus (HIV) infections are rarely acquired via an oral route in adults. Previous studies have shown that human whole saliva inhibits HIV infection in vitro, and multiple factors present in human saliva have been shown to contribute to this antiviral activity. Despite the widespread use of simian immunodeficiency virus (SIV)-infected rhesus macaques as models for HIV pathogenesis and transmission, few studies have monitored SIV in the oral cavity of infected rhesus macaques and evaluated the viral inhibitory capacity of macaque saliva. Utilizing a cohort of rhesus macaques infected with SIVMac251, we monitored virus levels and genotypic diversity in the saliva throughout the course of the disease; findings were similar to previous observations in HIV-infected humans. An in vitro infectivity assay was utilized to measure inhibition of HIV/SIV infection by normal human and rhesus macaque whole saliva. Both human and macaque saliva were capable of inhibiting HIV and SIV infection. The inhibitory capacity of saliva samples collected from a cohort of animals postinfection with SIV increased over the course of disease, coincident with the development of SIV-specific antibodies in the saliva. These findings suggest that both innate and adaptive factors contribute to inhibition of SIV by whole macaque saliva. This work also demonstrates that SIV-infected rhesus macaques provide a relevant model to examine the innate and adaptive immune responses that inhibit HIV/SIV in the oral cavity. PMID:20672998

  14. Conserved molecular signatures in gp120 are associated with the genetic bottleneck during simian immunodeficiency virus (SIV), SIV-human immunodeficiency virus (SHIV), and HIV type 1 (HIV-1) transmission.

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    Gonzalez, Mileidy W; DeVico, Anthony L; Lewis, George K; Spouge, John L

    2015-04-01

    Human immunodeficiency virus (HIV) transmission typically results from infection by a single transmitted/founder (T/F) variant. Are T/F variants chosen uniformly at random from the donor pool, or are they selected based on advantageous traits facilitating transmission? Finding evidence for selection during transmission is of particular interest, because it would indicate that phenotypic and/or genetic properties of the viruses might be harnessed as potential vaccine targets or immunotherapies. Here, we systematically evaluated the differences between the Env proteins of simian immunodeficiency virus/simian HIV (SIV/SHIV) stock and T/F variants in search of "signature" sites of transmission. We also surveyed residue preferences in HIV at the SIV/SHIV signature sites. Four sites of gp120 showed significant selection, and an additional two sites showed a similar trend. Therefore, the six sites clearly differentiate T/F viruses from the majority of circulating variants in the stocks. The selection of SIV/SHIV could be inferred reasonably across both vaccinated and unvaccinated subjects, with infections resulting from vaginal, rectal, and intravenous routes of transmission and regardless of viral dosage. The evidence for selection in SIV and SHIV T/F variants is strong and plentiful, and in HIV the evidence is suggestive though commensurate with the availability of suitable data for analysis. Two of the signature residues are completely conserved across the SIV, SHIV, and HIV variants we examined. Five of the signature residues map to the C1 region of gp120 and one to the signal peptide. Our data raise the possibility that C1, while governing the association between gp120 and gp41, modulates transmission efficiency, replicative fitness, and/or host cell tropism at the level of virus-cell attachment and entry. The present study finds significant evidence of selection on gp120 molecules of SIV/SHIV T/F viruses. The data provide ancillary evidence suggesting the same sites

  15. Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.

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    Félicien Moukambi

    2015-12-01

    Full Text Available Follicular T helper cells (Tfh, a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.

  16. Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

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    Deborah Heydenburg Fuller

    Full Text Available Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT, during antiretroviral therapy (ART induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans.

  17. Vaccination with Live Attenuated Simian Immunodeficiency Virus (SIV) Protects from Mucosal, but Not Necessarily Intravenous, Challenge with a Minimally Heterologous SIV.

    Science.gov (United States)

    Sutton, Matthew S; Burns, Charles M; Weiler, Andrea M; Balgeman, Alexis J; Braasch, Andrew; Lehrer-Brey, Gabrielle; Friedrich, Thomas C; O'Connor, Shelby L

    2016-06-15

    Few studies have evaluated the impact of the viral challenge route on protection against a heterologous simian immunodeficiency virus (SIV) challenge. We vaccinated seven macaques with a live attenuated SIV that differed from SIVmac239Δnef by 24 amino acids, called m3KOΔnef. All animals were protected from an intrarectal SIVmac239 challenge, whereas only four animals were protected from subsequent intravenous SIVmac239 challenge. These data suggest that immune responses elicited by vaccination with live attenuated SIV in an individual animal can confer protection from intrarectal challenge while remaining insufficient for protection from intravenous challenge. Our study is important because we show that vaccinated animals can be protected from a mucosal challenge with a heterologous SIV, but the same animals are not necessarily protected from intravenous challenge with the same virus. This is unique because in most studies, either vaccinated animals are challenged multiple times by the same route or only a single challenge is performed. An individually vaccinated animal is rarely challenged multiple times by different routes, so protection from different challenge routes cannot be measured in the same animal. Our data imply that vaccine-elicited responses in an individual animal may be insufficient for protection from intravenous challenge but may be suitable for protection from a mucosal challenge that better approximates human immunodeficiency virus (HIV) exposure. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  18. CD4 depletion in SIV-infected macaques results in macrophage and microglia infection with rapid turnover of infected cells.

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    Luca Micci

    2014-10-01

    Full Text Available In rhesus macaques (RMs, experimental depletion of CD4+ T-cells prior to SIV infection results in higher viremia and emergence of CD4-independent SIV-envelopes. In this study we used the rhesus recombinant anti-CD4 antibody CD4R1 to deplete RM CD4+ T-cells prior to SIVmac251 infection and investigate the sources of the increased viral burden and the lifespan of productively infected cells. CD4-depleted animals showed (i set-point viral load two-logs higher than controls; (ii macrophages constituting 80% of all SIV vRNA+ cells in lymph node and mucosal tissues; (iii substantial expansion of pro-inflammatory monocytes; (iv aberrant activation and infection of microglial cells; and (v lifespan of productively infected cells significantly longer in comparison to controls, but markedly shorter than previously estimated for macrophages. The net effect of CD4+ T-cell depletion is an inability to control SIV replication and a shift in the tropism of infected cells to macrophages, microglia, and, potentially, other CD4-low cells which all appear to have a shortened in vivo lifespan. We believe these findings have important implications for HIV eradication studies.

  19. Tissue-specific interferon alpha subtype response to SIV infection in brain, spleen, and lung.

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    Zaritsky, Luna Alammar; Dery, Alicia; Leong, Wan Yee; Gama, Lucio; Clements, Janice E

    2013-01-01

    Interferon alpha (IFNalpha) is a type I interferon that plays a major role in host defense. There are 13 different IFNalpha genes in humans, but much of the work concerning their role in viral defense has been limited to studying either subtype 2 or pan IFNalpha due to the inability to distinguish between highly similar genetic and amino acid sequences. Because of recent advances in molecular and biochemical techniques, it is possible to study the regulation of individual subtypes. It has been reported that HIV/SIV infection results in impaired IFNalpha responses in certain tissues. Using a pigtailed macaque SIV model, we examined the subtype response during acute infection in 3 tissues that are known to be infected with HIV/SIV, but whose IFNalpha subtype response has not been extensively studied: the brain, spleen, and lung. We found that the expression and regulation of specific subtypes occur in a tissue-specific manner. There was more limited IFNalpha subtype expression in the lung and brain, where predominantly macrophages are infected compared to the spleen, which contains both infected CD4+ lymphocytes and macrophages. Understanding the IFNalpha subtype response in tissues known to be infected with HIV/SIV can help tailor adjunctive treatment regimens to highly active antiretroviral therapy.

  20. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques.

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    Ivona Pandrea

    2016-01-01

    Full Text Available Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX and of gut inflammation (Sulfasalazine-SFZ. RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab-infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection.

  1. Identification and Structural Characterization of the ALIX-Binding Late Domains of Simian Immunodeficiency Virus SIV mac239 and SIV agmTan-1

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    Q Zhai; M Landesman; H Robinson; W Sundquist; C Hill

    2011-12-31

    Retroviral Gag proteins contain short late-domain motifs that recruit cellular ESCRT pathway proteins to facilitate virus budding. ALIX-binding late domains often contain the core consensus sequence YPX{sub n}L (where X{sub n} can vary in sequence and length). However, some simian immunodeficiency virus (SIV) Gag proteins lack this consensus sequence, yet still bind ALIX. We mapped divergent, ALIX-binding late domains within the p6{sup Gag} proteins of SIV{sub MAC239} ({sub 40}SREK{und P}YKE{und VT}ED{und L}LHLNSLF{sub 59}) and SIV{sub agmTan-1} ({sub 24}AAG{und A}YDP{und AR}KL{und L}EQYAKK{sub 41}). Crystal structures revealed that anchoring tyrosines (in lightface) and nearby hydrophobic residues (underlined) contact the ALIX V domain, revealing how lentiviruses employ a diverse family of late-domain sequences to bind ALIX and promote virus budding.

  2. Partial efficacy of a VSV-SIV/MVA-SIV vaccine regimen against oral SIV challenge in infant macaques.

    Science.gov (United States)

    Marthas, Marta L; Van Rompay, Koen K A; Abbott, Zachary; Earl, Patricia; Buonocore-Buzzelli, Linda; Moss, Bernard; Rose, Nina F; Rose, John K; Kozlowski, Pamela A; Abel, Kristina

    2011-04-12

    Despite antiretroviral medications, the rate of pediatric HIV-1 infections through breast-milk transmission has been staggering in developing countries. Therefore, the development of a vaccine to protect vulnerable infant populations should be actively pursued. We previously demonstrated that oral immunization of newborn macaques with vesicular stomatitis virus expressing simian immunodeficiency virus genes (VSV-SIV) followed 2 weeks later by an intramuscular boost with modified vaccinia ankara virus expressing SIV (MVA-SIV) successfully induced SIV-specific T and B cell responses in multiple lymphoid tissues, including the tonsil and intestine [13]. In the current study, we tested the oral VSV-SIV prime/systemic MVA-SIV boost vaccine for efficacy against multiple oral SIVmac251 challenges starting two weeks after the booster vaccination. The vaccine did not prevent SIV infection. However, in vaccinated infants, the level of SIV-specific plasma IgA (but not IgG) at the time of challenge was inversely correlated with peak viremia. In addition, the levels of SIV-specific IgA in saliva and plasma were inversely correlated with viral load at euthanasia. Animals with tonsils that contained higher frequencies of SIV-specific TNF-α- or IFN-γ-producing CD8(+) T cells and central memory T cells at euthanasia also had lower viremia. Interestingly, a marked depletion of CD25(+)FoxP3(+)CD4(+) T cells was observed in the tonsils as well as the intestine of these animals, implying that T regulatory cells may be a major target of SIV infection in infant macaques. Overall, the data suggest that, in infant macaques orally infected with SIV, the co-induction of local antiviral cytotoxic T cells and T regulatory cells that promote the development of IgA responses may result in better control of viral replication. Thus, future vaccination efforts should be directed towards induction of IgA and mucosal T cell responses to prevent or reduce virus replication in infants. Copyright

  3. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection

    Science.gov (United States)

    Damouche, Abderaouf; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

    2015-01-01

    Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic

  4. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

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    Abderaouf Damouche

    2015-09-01

    Full Text Available Two of the crucial aspects of human immunodeficiency virus (HIV infection are (i viral persistence in reservoirs (precluding viral eradication and (ii chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART-controlled HIV-infected patients. The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF; the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV. The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART. Data on the impact of HIV on the SVF (especially in individuals not receiving ART are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low

  5. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

    Science.gov (United States)

    Damouche, Abderaouf; Lazure, Thierry; Avettand-Fènoël, Véronique; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

    2015-09-01

    Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic

  6. Innate anti-viral immunity is associated with the protection elicited by the simian immunodeficiency virus (SIV) live attenuated virus vaccine in cynomolgus monkeys.

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    Goletti, Delia; Macchia, Iole; Leone, Pasqualina; Pace, Monica; Sernicola, Leonardo; Pavone-Cossut, Maria Rosaria; Maggiorella, Maria Teresa; Cafaro, Aurelio; Ensoli, Barbara; Titti, Fausto

    2006-10-01

    The Delta-nef live attenuated virus vaccine approach offered in the SIV-macaque model the opportunity to identify humoral and cell-mediated immune responses associated with protection against viral infections. In addition, soluble factors different from those related to specific immune responses appear to correlate with the establishment and maintenance of the protective status. Investigated were: 1) the ability of CD8+ T cells from cynomolgus monkeys vaccinated with SIV Delta-nef and long-term protected against sequential SIVs and SHIV challenges to inhibit in vitro SHIV replication in an acute infection cell system, 2) the ability of cell-free supernatants from CD8+ T cell cultures to inhibit replication of HIV in chronically infected cells, and 3) whether the antiviral activity of CD8+ T cells correlated with IFNgamma production. Soluble factor(s) secreted by CD8+ T cells from Delta-nef vaccinated monkeys significantly inhibited SHIV replication in an autologous cell system. This effect was not dependent on beta-chemokine secretion and correlated with an increased IFNgamma production. In addition, since supernatants from CD8+ T cells inhibited HIV production in chronically infected monocytic cells, the suppressive activity was not related to the viral strain. Vaccination with the live attenuated virus induces both a CD8+ T cell-dependent antiviral activity and IFNgamma responses potentially responsible for the protection from challenge with heterologous highly pathogenic SHIV89.6P. It is conceivable that boosting the "natural" along with the antigen-specific immunity is a desirable outcome to improve the protective efficacy of any vaccine approach.

  7. Divergent CD4+ T memory stem cell dynamics in pathogenic and nonpathogenic simian immunodeficiency virus infections.

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    Cartwright, Emily K; McGary, Colleen S; Cervasi, Barbara; Micci, Luca; Lawson, Benton; Elliott, Sarah T C; Collman, Ronald G; Bosinger, Steven E; Paiardini, Mirko; Vanderford, Thomas H; Chahroudi, Ann; Silvestri, Guido

    2014-05-15

    Recent studies have identified a subset of memory T cells with stem cell-like properties (T(SCM)) that include increased longevity and proliferative potential. In this study, we examined the dynamics of CD4(+) T(SCM) during pathogenic SIV infection of rhesus macaques (RM) and nonpathogenic SIV infection of sooty mangabeys (SM). Whereas SIV-infected RM show selective numeric preservation of CD4(+) T(SCM), SIV infection induced a complex perturbation of these cells defined by depletion of CD4(+)CCR5(+) T(SCM), increased rates of CD4(+) T(SCM) proliferation, and high levels of direct virus infection. The increased rates of CD4(+) T(SCM) proliferation in SIV-infected RM correlated inversely with the levels of central memory CD4(+) T cells. In contrast, nonpathogenic SIV infection of SM evidenced preservation of both CD4(+) T(SCM) and CD4(+) central memory T cells, with normal levels of CD4(+) T(SCM) proliferation, and lack of selective depletion of CD4(+)CCR5(+) T(SCM). Importantly, SIV DNA was below the detectable limit in CD4(+) T(SCM) from 8 of 10 SIV-infected SM. We propose that increased proliferation and infection of CD4(+) T(SCM) may contribute to the pathogenesis of SIV infection in RM.

  8. Hypercytotoxicity and rapid loss of NKp44+ innate lymphoid cells during acute SIV infection.

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    Haiying Li

    2014-12-01

    Full Text Available HIV/SIV infections break down the integrity of the gastrointestinal mucosa and lead to chronic immune activation and associated disease progression. Innate lymphoid cells (ILCs, distinguishable by high expression of NKp44 and RORγt, play key roles in mucosal defense and homeostasis, but are depleted from gastrointestinal (GI tract large bowel during chronic SIV infection. However, less is known about the kinetics of ILC loss, or if it occurs systemically. In acute SIV infection, we found a massive, up to 8-fold, loss of NKp44+ILCs in all mucosae as early as day 6 post-infection, which was sustained through chronic disease. Interestingly, no loss of ILCs was observed in mucosa-draining lymph nodes. In contrast, classical NK cells were not depleted either from gut or draining lymph nodes. Both ILCs and NK cells exhibited significantly increased levels of apoptosis as measured by increased Annexin-V expression, but while classical NK cells also showed increased proliferation, ILCs did not. Interestingly, ILCs, which are normally noncytolytic, dramatically upregulated cytotoxic functions in acute and chronic infection and acquired a polyfunctional phenotype secreting IFN-γ, MIP1-β, and TNF-α, but decreased production of the prototypical cytokine, IL-17. Classical NK cells had less dramatic functional change, but upregulated perforin expression and increased cytotoxic potential. Finally, we show that numerical and functional loss of ILCs was due to increased apoptosis and ROR γt suppression induced by inflammatory cytokines in the gut milieu. Herein we demonstrate the first evidence for acute, systemic, and permanent loss of mucosal ILCs during SIV infection associated with reduction of IL-17. The massive reduction of ILCs involves apoptosis without compensatory de novo development/proliferation, but the full mechanism of depletion and the impact of functional change so early in infection remain unclear.

  9. Immunization with single-cycle SIV significantly reduces viral loads after an intravenous challenge with SIV(mac239.

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    Bin Jia

    2009-01-01

    Full Text Available Strains of simian immunodeficiency virus (SIV that are limited to a single cycle of infection were evaluated for the ability to elicit protective immunity against wild-type SIV(mac239 infection of rhesus macaques by two different vaccine regimens. Six animals were inoculated at 8-week intervals with 6 identical doses consisting of a mixture of three different envelope variants of single-cycle SIV (scSIV. Six additional animals were primed with a mixture of cytoplasmic domain-truncated envelope variants of scSIV and boosted with two doses of vesicular stomatitis virus glycoprotein (VSV G trans-complemented scSIV. While both regimens elicited detectable virus-specific T cell responses, SIV-specific T cell frequencies were more than 10-fold higher after boosting with VSV G trans-complemented scSIV (VSV G scSIV. Broad T cell recognition of multiple viral antigens and Gag-specific CD4(+ T cell responses were also observed after boosting with VSV G scSIV. With the exception of a single animal in the repeated immunization group, all of the animals became infected following an intravenous challenge with SIV(mac239. However, significantly lower viral loads and higher memory CD4(+ T cell counts were observed in both immunized groups relative to an unvaccinated control group. Indeed, both scSIV immunization regimens resulted in containment of SIV(mac239 replication after challenge that was as good as, if not better than, what has been achieved by other non-persisting vaccine vectors that have been evaluated in this challenge model. Nevertheless, the extent of protection afforded by scSIV was not as good as typically conferred by persistent infection with live, attenuated SIV. These observations have potentially important implications to the design of an effective AIDS vaccine, since they suggest that ongoing stimulation of virus-specific immune responses may be essential to achieving the degree of protection afforded by live, attenuated SIV.

  10. Assembly of SIV virus-like particles containing envelope proteins using a baculovirus expression system.

    Science.gov (United States)

    Yamshchikov, G V; Ritter, G D; Vey, M; Compans, R W

    1995-12-01

    The requirements for SIV particle assembly and envelope incorporation were investigated using a baculovirus expression system. The Pr56gag precursor protein expressed under control of the polyhedrin promoter (pPolh) produced high levels of immature retrovirus-like particles (VLP) upon expression in Sf9 insect cells. To determine the optimal conditions for envelope protein (Env) incorporation into VLP, two recombinant baculoviruses expressing the SIV envelope protein under control of a very late pPolh or a hybrid late/very late capsid/polyhedrin (Pcap/polh) promoter and a recombinant expressing a truncated form of the SIV envelope protein (Envt) under the hybrid Pcap/polh promoter were compared. We have observed that utilization of the earlier hybrid promoter resulted in higher levels of Env expression on the cell surface and its incorporation into budding virus particles. We have also found that the Envt protein is transported to the cell surface of insect cells and incorporated into VLP more efficiently than full-length Env. In addition, we examined the effect of coexpression of the protease furin, which has been implicated in the proteolytic cleavage of the Env precursor gp160 in mammalian cells. Coexpression of furin in insect cells resulted in more efficient proteolytic cleavage into gp120 and gp41, and the cleaved proteins were incorporated into VLP.

  11. Multiplexed Component Analysis to Identify Genes Contributing to the Immune Response during Acute SIV Infection.

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    Iraj Hosseini

    Full Text Available Immune response genes play an important role during acute HIV and SIV infection. Using an SIV macaque model of AIDS and CNS disease, our overall goal was to assess how the expression of genes associated with immune and inflammatory responses are longitudinally changed in different organs or cells during SIV infection. To compare RNA expression of a panel of 88 immune-related genes across time points and among three tissues - spleen, mesenteric lymph nodes (MLN and peripheral blood mononuclear cells (PBMC - we designed a set of Nanostring probes. To identify significant genes during acute SIV infection and to investigate whether these genes are tissue-specific or have global roles, we introduce a novel multiplexed component analysis (MCA method. This combines multivariate analysis methods with multiple preprocessing methods to create a set of 12 "judges"; each judge emphasizes particular types of change in gene expression to which cells could respond, for example, the absolute or relative size of expression change from baseline. Compared to bivariate analysis methods, our MCA method improved classification rates. This analysis allows us to identify three categories of genes: (a consensus genes likely to contribute highly to the immune response; (b genes that would contribute highly to the immune response only if certain assumptions are met - e.g. that the cell responds to relative expression change rather than absolute expression change; and (c genes whose contribution to immune response appears to be modest. We then compared the results across the three tissues of interest; some genes are consistently highly-contributing in all tissues, while others are specific for certain tissues. Our analysis identified CCL8, CXCL10, CXCL11, MxA, OAS2, and OAS1 as top contributing genes, all of which are stimulated by type I interferon. This suggests that the cytokine storm during acute SIV infection is a systemic innate immune response against viral

  12. Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA on SIV-infected Chinese rhesus macaques.

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    Binhua Ling

    Full Text Available Viral reservoirs-persistent residual virus despite combination antiretroviral therapy (cART-remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM treated with intensive combination antiretroviral therapy (cART and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA.SIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations.Upon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters.The ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

  13. Generalized immune activation and innate immune responses in simian immunodeficiency virus infection.

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    Bosinger, Steven E; Sodora, Donald L; Silvestri, Guido

    2011-09-01

    Chronic immune activation is a key factor driving the immunopathogenesis of AIDS. During pathogenic HIV/simian immunodeficiency virus (SIV) infections, innate and adaptive antiviral immune responses contribute to chronic immune activation. In contrast, nonpathogenic SIV infections of natural hosts such as sooty mangabeys and African green monkeys (AGMs) are characterized by low immune activation despite similarly high viremia. This review focuses on the role of innate immune responses in SIV infection. Several studies have examined the role of innate immune responses to SIV as potential drivers of immune activation. The key result of these studies is that both pathogenic SIV infection of macaques and nonpathogenic SIV infections of natural hosts are associated with strong innate immune responses to the virus, high production of type I interferons by plasmacytoid dendritic cells, and upregulation of interferon-stimulated genes (ISGs). However, SIV-infected sooty mangabeys and AGMs (but not SIV-infected macaques) rapidly downmodulate the interferon response within 4-6 weeks of infection, thus resulting in a state of limited immune activation during chronic infection. Studies in nonhuman primates suggest that chronic innate/interferon responses may contribute to AIDS pathogenesis. Further, the ability of natural host species to resolve innate immune responses after infection provides a novel avenue for potential immunotherapy.

  14. Activation of the blood-brain barrier by SIV (simian immunodeficiency virus) requires cell-associated virus and is not restricted to endothelial cell activation.

    Science.gov (United States)

    MacLean, A G; Rasmussen, T A; Bieniemy, D; Lackner, A A

    2004-11-01

    The primary cell infected during acute HIV neuropathogenesis is the monocyte-derived macrophage. We have demonstrated that there is activation of the BBB (blood-brain barrier) during acute viral infection and at terminal AIDS. However, it has never been determined if there is a requirement for the virus to be carried through the BBB or how these Trojan horses would be induced to cross the BBB. We added SIVmac251-infected (SIV is simian immunodeficiency virus) mononuclear cells (and their supernatants) to the luminal or abluminal compartment of our BBB model. There was activation of both sides of the BBB model, only if viral-infected cells were added to the luminal compartment, as opposed to the addition of cell-free supernatants. This suggests that cell-associated virus is essential for the activation of the BBB. This, in turn, would be expected to lead to further infiltration of cells capable of viral infection. VCAM-1 (vascular cell adhesion molecule 1) staining revealed, for the first time, that there is an absolute requirement for virally infected cells, and not just the presence of virus for the activation of the BBB.

  15. Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection.

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    David Favre

    2009-02-01

    Full Text Available Chronic immune activation and progression to AIDS are observed after SIV infection in macaques but not in natural host primate species. To better understand this dichotomy, we compared acute pathogenic SIV infection in pigtailed macaques (PTs to non-pathogenic infection in African green monkeys (AGMs. SIVagm-infected PTs, but not SIVagm-infected AGMs, rapidly developed systemic immune activation, marked and selective depletion of IL-17-secreting (Th17 cells, and loss of the balance between Th17 and T regulatory (Treg cells in blood, lymphoid organs, and mucosal tissue. The loss of Th17 cells was found to be predictive of systemic and sustained T cell activation. Collectively, these data indicate that loss of the Th17 to Treg balance is related to SIV disease progression.

  16. Risk of immunodeficiency virus infection may increase with vaccine-induced immune response.

    Science.gov (United States)

    Tenbusch, Matthias; Ignatius, Ralf; Temchura, Vladimir; Nabi, Ghulam; Tippler, Bettina; Stewart-Jones, Guillaume; Salazar, Andres M; Sauermann, Ülrike; Stahl-Hennig, Christiane; Uberla, Klaus

    2012-10-01

    To explore the efficacy of novel complementary prime-boost immunization regimens in a nonhuman primate model for HIV infection, rhesus monkeys primed by different DNA vaccines were boosted with virus-like particles (VLP) and then challenged by repeated low-dose rectal exposure to simian immunodeficiency virus (SIV). Characteristic of the cellular immune response after the VLP booster immunization were high numbers of SIV-specific, gamma interferon-secreting cells after stimulation with inactivated SIV particles, but not SIV peptides, and the absence of detectable levels of CD8(+) T cell responses. Antibodies specific to SIV Gag and SIV Env could be induced in all animals, but, consistent with a poor neutralizing activity at the time of challenge, vaccinated monkeys were not protected from acquisition of infection and did not control viremia. Surprisingly, vaccinees with high numbers of SIV-specific, gamma interferon-secreting cells were infected fastest during the repeated low-dose exposures and the numbers of these immune cells in vaccinated macaques correlated with susceptibility to infection. Thus, in the absence of protective antibodies or cytotoxic T cell responses, vaccine-induced immune responses may increase the susceptibility to acquisition of immunodeficiency virus infection. The results are consistent with the hypothesis that virus-specific T helper cells mediate this detrimental effect and contribute to the inefficacy of past HIV vaccination attempts (e.g., STEP study).

  17. Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque.

    Science.gov (United States)

    Rotger, Margalida; Dalmau, Judith; Rauch, Andri; McLaren, Paul; Bosinger, Steven E; Martinez, Raquel; Sandler, Netanya G; Roque, Annelys; Liebner, Julia; Battegay, Manuel; Bernasconi, Enos; Descombes, Patrick; Erkizia, Itziar; Fellay, Jacques; Hirschel, Bernard; Miró, Jose M; Palou, Eduard; Hoffmann, Matthias; Massanella, Marta; Blanco, Julià; Woods, Matthew; Günthard, Huldrych F; de Bakker, Paul; Douek, Daniel C; Silvestri, Guido; Martinez-Picado, Javier; Telenti, Amalio

    2011-06-01

    High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4⁺ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4⁺ and CD8⁺ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4⁺ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.

  18. Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection.

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    Sama Adnan

    2016-12-01

    Full Text Available Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIVΔnef antigenic load. In conclusion, maturation of SIVΔnef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination.

  19. Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects.

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    Roff, Shannon R; Sanou, Missa P; Rathore, Mobeen H; Levy, Jay A; Yamamoto, Janet K

    2015-01-01

    Cross-reactive peptides on HIV-1 and FIV p24 protein sequences were studied using peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected long-term survivors (LTS; >10 y of infection without antiretroviral therapy, ART), short-term HIV-1 infected subjects not on ART, and ART-treated HIV-1 infected subjects. IFNγ-ELISpot and CFSE-proliferation analyses were performed with PBMC using overlapping HIV-1 and FIV p24 peptides. Over half of the HIV-1 infected subjects tested (22/31 or 71%) responded to one or more FIV p24 peptide pools by either IFNγ or T-cell proliferation analysis. PBMC and T cells from infected subjects in all 3 HIV(+) groups predominantly recognized one FIV p24 peptide pool (Fp14) by IFNγ production and one additional FIV p24 peptide pool (Fp9) by T-cell proliferation analysis. Furthermore, evaluation of overlapping SIV p24 peptide sequences identified conserved epitope(s) on the Fp14/Hp15-counterpart of SIV, Sp14, but none on Fp9-counterpart of SIV, Sp9. The responses to these FIV peptide pools were highly reproducible and persisted throughout 2-4 y of monitoring. Intracellular staining analysis for cytotoxins and phenotyping for CD107a determined that peptide epitopes from Fp9 and Fp14 pools induced cytotoxic T lymphocyte-associated molecules including perforin, granzyme B, granzyme A, and/or expression of CD107a. Selected FIV and corresponding SIV epitopes recognized by HIV-1 infected patients indicate that these protein sequences are evolutionarily conserved on both SIV and HIV-1 (e.g., Hp15:Fp14:Sp14). These studies demonstrate that comparative immunogenicity analysis of HIV-1, FIV, and SIV can identify evolutionarily-conserved T cell-associated lentiviral epitopes, which could be used as a vaccine for prophylaxis or immunotherapy.

  20. In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain

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    Joo Chan-Gyu

    2009-06-01

    Full Text Available Abstract Background In vivo proton magnetic resonance spectroscopy (1H-MRS studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection. Results Changes in the N-acetylaspartate (NAA, choline (Cho, myo-inositol (MI, creatine (Cr and glutamine/glutamate (Glx resonances were quantified both in absolute terms and relative to the creatine resonance. Most abnormalities were observed at the time of peak viremia, 2 weeks post infection (wpi. At that time point, significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex. Cr was significantly elevated only in the white matter. Changes in Cho and Cho/Cr were similar across the brain regions, increasing at 2 wpi, and falling below baseline levels at 4 wpi. MI and MI/Cr levels were increased across all brain regions. Conclusion These data best support the hypothesis that different brain regions have variable intrinsic vulnerabilities to neuronal injury caused by the AIDS virus.

  1. Risk of Immunodeficiency Virus Infection May Increase with Vaccine-Induced Immune Response

    OpenAIRE

    Tenbusch, Matthias; Ignatius, Ralf; Temchura, Vladimir; Nabi, Ghulam; Tippler, Bettina; Stewart-Jones, Guillaume; Salazar, Andres M.; Sauermann, Ulrike; Stahl-Hennig, Christiane; Überla, Klaus

    2012-01-01

    To explore the efficacy of novel complementary prime-boost immunization regimens in a nonhuman primate model for HIV infection, rhesus monkeys primed by different DNA vaccines were boosted with virus-like particles (VLP) and then challenged by repeated low-dose rectal exposure to simian immunodeficiency virus (SIV). Characteristic of the cellular immune response after the VLP booster immunization were high numbers of SIV-specific, gamma interferon-secreting cells after stimulation with inacti...

  2. Plasmacytoid dendritic cell dynamics tune interferon-alfa production in SIV-infected cynomolgus macaques.

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    Timothée Bruel

    2014-01-01

    Full Text Available IFN-I production is a characteristic of HIV/SIV primary infections. However, acute IFN-I plasma concentrations rapidly decline thereafter. Plasmacytoid dendritic cells (pDC are key players in this production but primary infection is associated with decreased responsiveness of pDC to TLR 7 and 9 triggering. IFNα production during primary SIV infection contrasts with increased pDC death, renewal and dysfunction. We investigated the contribution of pDC dynamics to both acute IFNα production and the rapid return of IFNα concentrations to pre-infection levels during acute-to-chronic transition. Nine cynomolgus macaques were infected with SIVmac251 and IFNα-producing cells were quantified and characterized. The plasma IFN-I peak was temporally associated with the presence of IFNα(+ pDC in tissues but IFN-I production was not detectable during the acute-to-chronic transition despite persistent immune activation. No IFNα(+ cells other than pDC were detected by intracellular staining. Blood-pDC and peripheral lymph node-pDC both lost IFNα(- production ability in parallel. In blood, this phenomenon correlated with an increase in the counts of Ki67(+-pDC precursors with no IFNα production ability. In tissues, it was associated with increase of both activated pDC and KI67(+-pDC precursors, none of these being IFNα(+ in vivo. Our findings also indicate that activation/death-driven pDC renewal rapidly blunts acute IFNα production in vivo: pDC sub-populations with no IFNα-production ability rapidly increase and shrinkage of IFNα production thus involves both early pDC exhaustion, and increase of pDC precursors.

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

    Science.gov (United States)

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

    2011-12-01

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

  4. A Novel Approach for Producing Lentiviruses That Are Limited to a Single Cycle of Infection

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    Evans, David T.; Bricker, Jennifer E.; Desrosiers, Ronald C.

    2004-01-01

    We have devised a novel approach for producing simian immunodeficiency virus (SIV) strains and, potentially, human immunodeficiency virus type 1 (HIV-1) strains that are limited to a single cycle of infection. Unlike previous lentiviral vectors, our single-cycle SIV is capable of expressing eight of the nine viral gene products and infected cells release immature virus particles that are unable to complete subsequent rounds of infection. Single-cycle SIV (scSIV) was produced by using a two-pl...

  5. SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination.

    Science.gov (United States)

    Klatt, Nichole R; Vinton, Carol L; Lynch, Rebecca M; Canary, Lauren A; Ho, Jason; Darrah, Patricia A; Estes, Jacob D; Seder, Robert A; Moir, Susan L; Brenchley, Jason M

    2011-11-24

    HIV infection is characterized by immune system dysregulation, including depletion of CD4+ T cells, immune activation, and abnormal B- and T-cell responses. However, the immunologic mechanisms underlying lymphocytic dysfunctionality and whether it is restricted to immune responses against neo antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC adjuvant. We found that vaccinated SIVuninfected animals induced high frequencies of polyfunctional MML-specific CD4+ T cells. However, in SIV-infected animals, CD4+ T-cell functionality decreased after both neo (P = .0025) and recall (P = .0080) MML vaccination. Furthermore, after SIV infection, the frequency of MML-specific antibody-secreting classic memory B cells was decreased compared with vaccinated, SIV-uninfected animals. Specifically, antibody-secreting classic memory B cells that produced IgA in response to either neo (P = .0221) or recall (P = .0356) MML vaccinations were decreased. Furthermore, we found that T-follicular helper cells, which are essential for priming B cells, are preferentially infected with SIV. These data indicate that SIV infection results in dysfunctional T-cell responses to neo and recall vaccinations, and direct SIV infection of T-follicular helper cells, both of which probably contribute to deficient B-cell responses and, presumably, susceptibility to certain opportunistic infections.

  6. HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells

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    John Zaunders

    2017-04-01

    Full Text Available BackgroundT follicular helper (Tfh cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4+ T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells.MethodologyTfh and other CD4+ T cell subsets from macaque lymph nodes and spleens, splenic Tfh from HIV+ subjects, and tonsillar Tfh from HIV-uninfected subjects were isolated by cell sorting prior to cell surface and molecular characterization. HIV proviral gp120 sequences were submitted to genotypic and phenotypic tropism assays. Entry of CCR5- and CXCR4-using viruses into Tfh from uninfected tonsillar tissue was measured using a fusion assay.ResultsPhylogenetic analysis, genotypic, and phenotypic analysis showed that splenic Tfh cells from chronic HIV+ subjects were predominantly infected with CCR5-using viruses. In macaques, purified CCR5+PD-1intermediate(int+ memory CD4+ T cells were shown to include pre-Tfh cells capable of differentiating in vitro to Tfh by upregulation of PD-1 and Bcl6, confirmed by qRT-PCR and single-cell multiplex PCR. Infected PD-1int cells survive, carry SIV provirus, and differentiate into PD-1hi Tfh after T cell receptor stimulation, suggesting a pathway for SIV infection of Tfh. In addition, a small subset of macaque and human PD-1hi Tfh can express low levels of CCR5, which makes them susceptible to infection. Fusion assays demonstrated CCR5-using HIV-1 entry into CCR5+ Tfh and pre-Tfh cells from human tonsils.ConclusionThe major route of infection of Tfh in macaques and humans appears to be via a CCR5-expressing pre-Tfh population

  7. Stability of the gorilla microbiome despite simian immunodeficiency virus infection.

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

    2015-02-01

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

  8. Virus Infection

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    Hiroshi Abe

    2013-01-01

    Full Text Available Of 168 patients with chronic hepatitis B virus (HBV infection-related liver disease, 20 patients who had received 100 mg of lamivudine plus 10 mg/day of adefovir dipivoxil (ADV (ADV group and 124 patients who had received 0.5 mg/day of entecavir or 100 mg/day of lamivudine (non-ADV group for >1 year were enrolled. For comparative analyses, 19 well-matched pairs were obtained from the groups by propensity scores. At the time of enrollment, serum creatinine and phosphate concentrations were similar between the ADV and non-ADV groups; however, urinary phosphate ( and serum bone-specific alkaline phosphatase (BAP ( concentrations were significantly higher in the ADV group than in the non-ADV group. Serum BAP was significantly higher at the time of enrollment than before ADV administration in the ADV group (, although there was no significant change in serum BAP concentration in the non-ADV group. There was a significant positive correlation between the period of ADV therapy and ΔBAP (, . Serum BAP concentration increased before increase in serum creatinine concentration and was useful for early detection of adverse events and for developing adequate measures for continuing ADV for chronic HBV infection-related liver disease.

  9. IL-17-producing innate lymphoid cells are restricted to mucosal tissues and are depleted in SIV-infected macaques

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    Xu, Huanbin; Wang, Xiaolei; Liu, David X.; Moroney-Rasmussen, Terri; Lackner, Andrew A.; Veazey, Ronald S.

    2013-01-01

    SUMMARY Innate lymphoid cells (ILCs) are an emerging subset of lymphocytes involved in surveillance against virally infected cells. Here we show CD3−CD8high lymphocytes in macaque blood include major subsets of ILCs including NK cells expressing CD16, NKp46 and NKG2A, but also populations of ILCs in mucosal tissues having different properties. One ILC subset secreted IL-17 (ILC17), but these were restricted to mucosal tissues. Some mucosal ILC17 cells expressed classical NK-cell markers, but little NKG2A or NKG2D. Some ILC17 cells secreted IL-22 and TNF-α, but few produced IFN-γ or contained granzyme B. IL-17 production by ILCs was induced by IL-6, TGF-β and IL-23. Further, SIV infection resulted in a significant loss of ILC17 cells, especially in the jejunum, which persisted throughout SIV infection. These findings ILC17 cells may be involved in innate mucosal immune responses, and their loss may contribute to loss of intestinal mucosal integrity and disease progression in HIV/SIV infection. PMID:22669579

  10. Altered immune responses in rhesus macaques co-infected with SIV and Plasmodium cynomolgi: an animal model for coincident AIDS and relapsing malaria.

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    Jeffrey W Koehler

    2009-09-01

    Full Text Available Dual epidemics of the malaria parasite Plasmodium and HIV-1 in sub-Saharan Africa and Asia present a significant risk for co-infection in these overlapping endemic regions. Recent studies of HIV/Plasmodium falciparum co-infection have reported significant interactions of these pathogens, including more rapid CD4+ T cell loss, increased viral load, increased immunosuppression, and increased episodes of clinical malaria. Here, we describe a novel rhesus macaque model for co-infection that supports and expands upon findings in human co-infection studies and can be used to identify interactions between these two pathogens.Five rhesus macaques were infected with P. cynomolgi and, following three parasite relapses, with SIV. Compared to macaques infected with SIV alone, co-infected animals had, as a group, decreased survival time and more rapid declines in markers for SIV progression, including peripheral CD4+ T cells and CD4+/CD8+ T cell ratios. The naïve CD4+ T cell pool of the co-infected animals was depleted more rapidly than animals infected with SIV alone. The co-infected animals also failed to generate proliferative responses to parasitemia by CD4+ and CD8+ T cells as well as B cells while also having a less robust anti-parasite and altered anti-SIV antibody response.These data suggest that infection with both SIV and Plasmodium enhances SIV-induced disease progression and impairs the anti-Plasmodium immune response. These data support findings in HIV/Plasmodium co-infection studies. This animal model can be used to further define impacts of lentivirus and Plasmodium co-infection and guide public health and therapeutic interventions.

  11. Visualizing the Immune System: Providing Key Insights into HIV/SIV Infections

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    Jacob D. Estes

    2018-03-01

    Full Text Available Immunological inductive tissues, such as secondary lymphoid organs, are composed of distinct anatomical microenvironments for the generation of immune responses to pathogens and immunogens. These microenvironments are characterized by the compartmentalization of highly specialized immune and stromal cell populations, as well as the presence of a complex network of soluble factors and chemokines that direct the intra-tissue trafficking of naïve and effector cell populations. Imaging platforms have provided critical contextual information regarding the molecular and cellular interactions that orchestrate the spatial microanatomy of relevant cells and the development of immune responses against pathogens. Particularly in HIV/SIV disease, imaging technologies are of great importance in the investigation of the local interplay between the virus and host cells, with respect to understanding viral dynamics and persistence, immune responses (i.e., adaptive and innate inflammatory responses, tissue structure and pathologies, and changes to the surrounding milieu and function of immune cells. Merging imaging platforms with other cutting-edge technologies could lead to novel findings regarding the phenotype, function, and molecular signatures of particular immune cell targets, further promoting the development of new antiviral treatments and vaccination strategies.

  12. Rapid Dissemination of SIV Follows Multisite Entry after Rectal Inoculation

    Science.gov (United States)

    Prétet, Jean-Luc; Michel-Salzat, Alice; Messent, Valérie; Bogdanova, Anna; Couëdel-Courteille, Anne; Souil, Evelyne; Cheynier, Rémi; Butor, Cécile

    2011-01-01

    Receptive ano-rectal intercourse is a major cause of HIV infection in men having sex with men and in heterosexuals. Current knowledge of the mechanisms of entry and dissemination during HIV rectal transmission is scarce and does not allow the development of preventive strategies. We investigated the early steps of rectal infection in rhesus macaques inoculated with the pathogenic isolate SIVmac251 and necropsied four hours to nine days later. All macaques were positive for SIV. Control macaques inoculated with heat-inactivated virus were consistently negative for SIV. SIV DNA was detected in the rectum as early as four hours post infection by nested PCR for gag in many laser-microdissected samples of lymphoid aggregates and lamina propria but never in follicle-associated epithelium. Scarce SIV antigen positive cells were observed by immunohistofluorescence in the rectum, among intraepithelial and lamina propria cells as well as in clusters in lymphoid aggregates, four hours post infection and onwards. These cells were T cells and non-T cells that were not epithelial cells, CD68+ macrophages, DC-SIGN+ cells or fascin+ dendritic cells. DC-SIGN+ cells carried infectious virus. Detection of Env singly spliced mRNA in the mucosa by nested RT-PCR indicated ongoing viral replication. Strikingly, four hours post infection colic lymph nodes were also infected in all macaques as either SIV DNA or infectious virus was recovered. Rapid SIV entry and dissemination is consistent with trans-epithelial transport. Virions appear to cross the follicle-associated epithelium, and also the digestive epithelium. Viral replication could however be more efficient in lymphoid aggregates. The initial sequence of events differs from both vaginal and oral infections, which implies that prevention strategies for rectal transmission will have to be specific. Microbicides will need to protect both digestive and follicle-associated epithelia. Vaccines will need to induce immunity in lymph nodes

  13. Dating the age of the SIV lineages that gave rise to HIV-1 and HIV-2.

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    Joel O Wertheim

    2009-05-01

    Full Text Available Great strides have been made in understanding the evolutionary history of simian immunodeficiency virus (SIV and the zoonoses that gave rise to HIV-1 and HIV-2. What remains unknown is how long these SIVs had been circulating in non-human primates before the transmissions to humans. Here, we use relaxed molecular clock dating techniques to estimate the time of most recent common ancestor for the SIVs infecting chimpanzees and sooty mangabeys, the reservoirs of HIV-1 and HIV-2, respectively. The date of the most recent common ancestor of SIV in chimpanzees is estimated to be 1492 (1266-1685, and the date in sooty mangabeys is estimated to be 1809 (1729-1875. Notably, we demonstrate that SIV sequences sampled from sooty mangabeys possess sufficient clock-like signal to calibrate a molecular clock; despite the differences in host biology and viral dynamics, the rate of evolution of SIV in sooty mangabeys is indistinguishable from that of its human counterpart, HIV-2. We also estimate the ages of the HIV-2 human-to-human transmissible lineages and provide the first age estimate for HIV-1 group N at 1963 (1948-1977. Comparisons between the SIV most recent common ancestor dates and those of the HIV lineages suggest a difference on the order of only hundreds of years. Our results suggest either that SIV is a surprisingly young lentiviral lineage or that SIV and, perhaps, HIV dating estimates are seriously compromised by unaccounted-for biases.

  14. Loss of effector and anti-inflammatory natural killer T lymphocyte function in pathogenic simian immunodeficiency virus infection.

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    Namita Rout

    2012-09-01

    Full Text Available Chronic immune activation is a key determinant of AIDS progression in HIV-infected humans and simian immunodeficiency virus (SIV-infected macaques but is singularly absent in SIV-infected natural hosts. To investigate whether natural killer T (NKT lymphocytes contribute to the differential modulation of immune activation in AIDS-susceptible and AIDS-resistant hosts, we compared NKT function in macaques and sooty mangabeys in the absence and presence of SIV infection. Cynomolgus macaques had significantly higher frequencies of circulating invariant NKT lymphocytes compared to both rhesus macaques and AIDS-resistant sooty mangabeys. Despite this difference, mangabey NKT lymphocytes were functionally distinct from both macaque species in their ability to secrete significantly more IFN-γ, IL-13, and IL-17 in response to CD1d/α-galactosylceramide stimulation. While NKT number and function remained intact in SIV-infected mangabeys, there was a profound reduction in NKT activation-induced, but not mitogen-induced, secretion of IFN-γ, IL-2, IL-10, and TGF-β in SIV-infected macaques. SIV-infected macaques also showed a selective decline in CD4(+ NKT lymphocytes which correlated significantly with an increase in circulating activated memory CD4(+ T lymphocytes. Macaques with lower pre-infection NKT frequencies showed a significantly greater CD4(+ T lymphocyte decline post SIV infection. The disparate effect of SIV infection on NKT function in mangabeys and macaques could be a manifestation of their differential susceptibility to AIDS. Alternately, these data also raise the possibility that loss of anti-inflammatory NKT function promotes chronic immune activation in pathogenic SIV infection, while intact NKT function helps to protect natural hosts from developing immunodeficiency and aberrant immune activation.

  15. Dynamics of Simian Immunodeficiency Virus SIVmac239 Infection in Pigtail Macaques

    Science.gov (United States)

    Klatt, Nichole R.; Canary, Lauren A.; Vanderford, Thomas H.; Vinton, Carol L.; Engram, Jessica C.; Dunham, Richard M.; Cronise, Heather E.; Swerczek, Joanna M.; Lafont, Bernard A. P.; Picker, Louis J.; Silvestri, Guido

    2012-01-01

    Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P = 0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P = 0.7953 and P = 0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4+ T cell depletion, as CD4+ T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression. PMID:22090099

  16. Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL-21.

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    Suresh Pallikkuth

    Full Text Available In pathogenic HIV and SIV infections of humans and rhesus macaques (RMs, preferential depletion of CD4⁺ Th17 cells correlates with mucosal immune dysfunction and disease progression. Interleukin (IL-21 promotes differentiation of Th17 cells, long-term maintenance of functional CD8⁺ T cells, and differentiation of memory B cells and antibody-secreting plasma cells. We hypothesized that administration of IL-21 will improve mucosal function in the context of pathogenic HIV/SIV infections. To test this hypothesis, we infected 12 RMs with SIV(mac239 and at day 14 post-infection treated six of them with rhesus rIL-21-IgFc. IL-21-treatment was safe and did not increase plasma viral load or systemic immune activation. Compared to untreated animals, IL-21-treated RMs showed (i higher expression of perforin and granzyme B in total and SIV-specific CD8⁺ T cells and (ii higher levels of intestinal Th17 cells. Remarkably, increased levels of Th17 cells were associated with reduced levels of intestinal T cell proliferation, microbial translocation and systemic activation/inflammation in the chronic infection. In conclusion, IL-21-treatment in SIV-infected RMs improved mucosal immune function through enhanced preservation of Th17 cells. Further preclinical studies of IL-21 may be warranted to test its potential use during chronic infection in conjunction with antiretroviral therapy.

  17. Evaluation of the safety, immunogenicity, and protective efficacy of whole inactivated simian immunodeficiency virus (SIV) vaccines with conformationally and functionally intact envelope glycoproteins.

    Science.gov (United States)

    Lifson, Jeffrey D; Rossio, Jeffrey L; Piatak, Michael; Bess, Julian; Chertova, Elena; Schneider, Douglas K; Coalter, Vicky J; Poore, Barbara; Kiser, Rebecca F; Imming, Robert J; Scarzello, Anthony J; Henderson, Louis E; Alvord, W Gregory; Hirsch, Vanessa M; Benveniste, Raoul E; Arthur, Larry O

    2004-07-01

    A novel, general approach to chemical inactivation of retroviruses was used to produce inactivated simian immunodeficiency virus (SIV) particles with functional envelope glycoproteins. Inactivated virions of three different virus isolates (SIVmne E11S, SIVmac239, and SIVmac239 g4,5), prepared by treatment with 2,2'-dithiodipyridine (aldrithol-2, AT-2), were not detectably infectious, in vitro or in vivo. Immunization of pigtailed macaques with inactivated SIVmne E11S particles, without adjuvant, induced both humoral and cellular immune responses. Four of six animals immunized with the inactivated particles did not show measurable SIV RNA in plasma (virus (SIVmne E11S), compared to peak values of > or =10(6) copy Eq/ml in challenged SIV-naive control animals (p = 0.0001). Despite the absence of measurable viral RNA in plasma in these animals, culturable virus and viral DNA were initially detectable in blood and lymph node specimens; in contrast to control animals, SIV DNA could no longer be detected in PBMC by 10 weeks postchallenge in five of six SIV-immunized animals (p = 0.0001). However, vaccines did not resist a sequential rechallenge with the heterologous pathogenic virus SIVsm E660. AT-2-inactivated virus with functional envelope glycoproteins is a novel class of vaccine immunogen and was noninfectious, under conditions of rigorous in vivo challenge, and induced both binding and neutralizing antibody responses, along with cellular immune responses. Results suggest that immunization facilitated effective containment of pathogenic homologous challenge virus. With further optimization, AT-2-inactivated viral particles may be a useful class of immunogen in the development of a vaccine to prevent AIDS.

  18. Viral RNA levels and env variants in semen and tissues of mature male rhesus macaques infected with SIV by penile inoculation.

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    Francis Fieni

    Full Text Available HIV is shed in semen but the anatomic site of virus entry into the genital secretions is unknown. We determined viral RNA (vRNA levels and the envelope gene sequence in the SIVmac 251 viral populations in the genital tract and semen of 5 adult male rhesus monkeys (Macaca mulatta that were infected after experimental penile SIV infection. Paired blood and semen samples were collected from 1-9 weeks after infection and the monkeys were necropsied eleven weeks after infection. The axillary lymph nodes, testes, epididymis, prostate, and seminal vesicles were collected and vRNA levels and single-genome analysis of the SIVmac251 env variants was performed. At the time of semen collection, blood vRNA levels were between 3.09 and 7.85 log10 vRNA copies/ml plasma. SIV RNA was found in the axillary lymph nodes of all five monkeys and in 3 of 5 monkeys, all tissues examined were vRNA positive. In these 3 monkeys, vRNA levels (log10 SIVgag copies/ug of total tissue RNA in the axillary lymph node (6.48 ± 0.50 were significantly higher than in the genital tract tissues: testis (3.67 ± 2.16; p<0.05, epididymis (3.08 ± 1.19; p<0.0001, prostate (3.36 ± 1.30; p<0.01, and seminal vesicle (2.67 ± 1.50; p<0.0001. Comparison of the SIVmac251 env viral populations in blood plasma, systemic lymph node, and genital tract tissues was performed in two of the macaques. Visual inspection of the Neighbor-Joining phylograms revealed that in both animals, all the sequences were generally distributed evenly among all tissue compartments. Importantly, viral populations in the genital tissues were not distinct from those in the systemic tissues. Our findings demonstrate striking similarity in the viral populations in the blood and male genital tract tissues within 3 months of penile SIV transmission.

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

    Science.gov (United States)

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

    2014-01-01

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

  20. Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques

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    Vargas-Inchaustegui, Diego A.; Xiao, Peng; Hogg, Alison E.; Demberg, Thorsten; McKinnon, Katherine [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Venzon, David [Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Brocca-Cofano, Egidio; DiPasquale, Janet [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Lee, Eun M.; Hudacik, Lauren; Pal, Ranajit [Advanced Bioscience Laboratories Inc., Rockville, MD 20850 (United States); Sui, Yongjun; Berzofsky, Jay A. [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Liu, Linda; Langermann, Solomon [Amplimmune Inc., Gaithersburg, MD 20878 (United States); Robert-Guroff, Marjorie, E-mail: guroffm@mail.nih.gov [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-12-15

    High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. We evaluated the phenotype and distribution of T cells and Tregs during antiretroviral therapy plus PD-1 modulation (using a B7-DC-Ig fusion protein) and post-ART. Chronically SIV-infected rhesus macaques received: 11 weeks of ART (Group A); 11 weeks of ART plus B7-DC-Ig (Group B); 11 weeks of ART plus B7-DC-Ig, then 12 weeks of B7-DC-Ig alone (Group C). Continuous B7-DC-Ig treatment (Group C) decreased rebound viremia post-ART compared to pre-ART levels, associated with decreased PD-1{sup hi} expressing T cells and Tregs in PBMCs, and PD-1{sup hi} Tregs in lymph nodes. It transiently decreased expression of Ki67 and α{sub 4}β{sub 7} in PBMC CD4{sup +} and CD8{sup +} Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1{sup hi} cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses. - Highlights: • B7-DC-Ig modulates PD-1{sup hi} cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1{sup hi} cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire.

  1. Clinical monitoring and correlates of nephropathy in SIV-infected macaques during high-dose antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Hebblewaite Diane

    2011-01-01

    Full Text Available Abstract Background In many preclinical AIDS research studies, antiretroviral therapy (ART is administered to experimentally simian immunodeficiency (SIV-infected rhesus macaques for reduction of viral load to undetectable levels. Prolonged treatment of macaques with a high dose of PMPA (9-[2-(r-(phosphonomethoxy propyl] adenine or tenofovir; 30 mg/kg of body weight subcutaneously once daily can result in proximal renal tubular dysfunction, a Fanconi-like syndrome characterized by glucosuria, aminoaciduria, hypophosphatemia, and bone pathology. In contrast, chronic administration of a low dose of PMPA (10 mg/kg subcutaneously once daily starting at birth does not seem to be associated with any adverse health effects within 3 years of treatment. In contrast to PMPA, limited information on systemic toxicity in rhesus monkeys is available for FTC (5-fluoro-1-(2R,5S-[2-(hydroxymethyl-1,3-oxathiolan-5-yl]cytosine; emtricitabine and stavudine (d4T. Results In this study, the clinical and biochemical correlates of tubular nephrosis in SIV-infected rhesus macaques associated with systemic administration of high-dose ART consisting of the three nucleoside analog inhibitors PMPA, FTC, and d4T were investigated. It was found that acute renal failure was uncommon (7.1% of treated animals and that morphologic evidence of nephropathy, which persisted for more than 300 days following discontinuation of the drug cocktail, was more frequent (52.4% of treated animals. While parameters from single time points lacked predictive value, biochemical alterations in Blood Urea Nitrogen (BUN and phosphorus were frequently identified longitudinally in the blood of ART-treated animals that developed evidence of nephropathy, and these longitudinal changes correlated with disease severity. Conclusions Recommendations are proposed to limit the impact of drug-induced renal disease in future SIV macaque studies.

  2. Viruses Infecting Reptiles

    Science.gov (United States)

    Marschang, Rachel E.

    2011-01-01

    A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch’s postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions. PMID:22163336

  3. Viruses Infecting Reptiles

    Directory of Open Access Journals (Sweden)

    Rachel E. Marschang

    2011-11-01

    Full Text Available A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch’s postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions.

  4. Viruses infecting reptiles.

    Science.gov (United States)

    Marschang, Rachel E

    2011-11-01

    A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch's postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions.

  5. Mapping the small RNA content of simian immunodeficiency virions (SIV.

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    Markus Brameier

    Full Text Available Recent evidence indicates that regulatory small non-coding RNAs are not only components of eukaryotic cells and vesicles, but also reside within a number of different viruses including retroviral particles. Using ultra-deep sequencing we have comprehensively analyzed the content of simian immunodeficiency virions (SIV, which were compared to mock-control preparations. Our analysis revealed that more than 428,000 sequence reads matched the SIV mac239 genome sequence. Among these we could identify 12 virus-derived small RNAs (vsRNAs that were highly abundant. Beside known retrovirus-enriched small RNAs, like 7SL-RNA, tRNA(Lys3 and tRNA(Lys isoacceptors, we also identified defined fragments derived from small ILF3/NF90-associated RNA snaR-A14, that were enriched more than 50 fold in SIV. We also found evidence that small nucleolar RNAs U2 and U12 were underrepresented in the SIV preparation, indicating that the relative number or the content of co-isolated exosomes was changed upon infection. Our comprehensive atlas of SIV-incorporated small RNAs provides a refined picture of the composition of retrovirions, which gives novel insights into viral packaging.

  6. Mechanisms of CD8+ T cell-mediated suppression of HIV/SIV replication.

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    McBrien, Julia Bergild; Kumar, Nitasha A; Silvestri, Guido

    2018-02-10

    In this article, we summarize the role of CD8+ T cells during natural and ART-treated HIV and SIV infections, discuss the mechanisms responsible for their suppressive activity, and review the rationale for CD8+ T cell-based HIV cure strategies. Evidence suggests that CD8+ T cells are involved in the control of virus replication during HIV and SIV infections. During early HIV infection, the cytolytic activity of CD8+ T cells is responsible for control of viremia. However, it has been proposed that CD8+ T cells also use non-cytolytic mechanisms to control SIV infection. More recently, CD8+ T cells were shown to be required to fully suppress virus production in ART-treated SIV-infected macaques, suggesting that CD8+ T cells are involved in the control of virus transcription in latently infected cells that persist under ART. A better understanding of the complex antiviral activities of CD8+ T cells during HIV/SIV infection will pave the way for immune interventions aimed at harnessing these functions to target the HIV reservoir. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

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    Jennifer H Campbell

    2014-12-01

    Full Text Available Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab once a week for three weeks beginning on 28 days post-infection (late. Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS, and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+ in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  8. [Genetic diversity and phylogeographic distribution of SIV: how to understand the origin of HIV].

    Science.gov (United States)

    Peeters, Martine; Chaix, Marie-Laure; Delaporte, Eric

    2008-01-01

    Emergence of human immunodeficiency viruses HIV-1 and HIV-2 results from interspecies transmission from simian viruses SIV. SIVcpzPtt infecting chimpanzees, and from which the HIV-1 (subgroups M and N) is derived is still found in the Pan troglodytes troglodytes population of south Cameroon chimpanzees. The ancestor of HIV-1 group O, is found in the Gorilla residing in Western Africa, but chimpanzees are in fact the initial reservoir of the SIV viruses SIVgor, and it is still unclear whether the group O HIV-1 has been transmitted to humans by gorillas and/or chimpanzees. At least eight interspecies transmissions between and humans implicating SIVsmm (from sooty mangabey monkeys) have occurred, corresponding to the eight VIH-2 groups. Since habits of hunting and meat preparation in the bush still persistently expose humans in Africa to SIV infection, new interspecies transmission of these viruses remains a possibility.

  9. Simian Immunodeficiency Virus Infects Follicular Helper CD4 T Cells in Lymphoid Tissues during Pathogenic Infection of Pigtail Macaques

    Science.gov (United States)

    Xu, Yin; Weatherall, Chris; Bailey, Michelle; Alcantara, Sheilajen; De Rose, Robert; Estaquier, Jerome; Wilson, Kim; Suzuki, Kazuo; Corbeil, Jacques; Cooper, David A.; Kent, Stephen J.; Kelleher, Anthony D.

    2013-01-01

    T follicular helper (Tfh) cells are a specialized subset of memory CD4+ T cells that are found exclusively within the germinal centers of secondary lymphoid tissues and are important for adaptive antibody responses and B cell memory. Tfh cells do not express CCR5, the primary entry coreceptor for both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), and therefore, we hypothesized that these cells would avoid infection. We studied lymph nodes and spleens from pigtail macaques infected with pathogenic strain SIVmac239 or SIVmac251, to investigate the susceptibility of Tfh cells to SIV infection. Pigtail macaque PD-1high CD127low memory CD4+ T cells have a phenotype comparable to that of human Tfh cells, expressing high levels of CXCR5, interleukin-21 (IL-21), Bcl-6, and inducible T cell costimulator (ICOS). As judged by either proviral DNA or cell-associated viral RNA measurements, macaque Tfh cells were infected with SIV at levels comparable to those in other CD4+ memory T cells. Infection of macaque Tfh cells was evident within weeks of inoculation, yet we confirmed that Tfh cells do not express CCR5 or either of the well-known alternative SIV coreceptors, CXCR6 and GPR15. Mutations in the SIV envelope gp120 region occurred in chronically infected macaques but were uniform across each T cell subset investigated, indicating that the viruses used the same coreceptors to enter different cell subsets. Early infection of Tfh cells represents an unexpected focus of viral infection. Infection of Tfh cells does not interrupt antibody production but may be a factor that limits the quality of antibody responses and has implications for assessing the size of the viral reservoir. PMID:23325697

  10. Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL

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    Maria S. Salvato

    2007-01-01

    Full Text Available Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4- lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203. Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques.

  11. Inefficient Nef-mediated downmodulation of CD3 and MHC-I correlates with loss of CD4+T cells in natural SIV infection.

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    Michael Schindler

    2008-07-01

    Full Text Available Recent data suggest that Nef-mediated downmodulation of TCR-CD3 may protect SIVsmm-infected sooty mangabeys (SMs against the loss of CD4+ T cells. However, the mechanisms underlying this protective effect remain unclear. To further assess the role of Nef in nonpathogenic SIV infection, we cloned nef alleles from 11 SIVsmm-infected SMs with high (>500 and 15 animals with low (<500 CD4+ T-cells/microl in bulk into proviral HIV-1 IRES/eGFP constructs and analyzed their effects on the phenotype, activation, and apoptosis of primary T cells. We found that not only efficient Nef-mediated downmodulation of TCR-CD3 but also of MHC-I correlated with preserved CD4+ T cell counts, as well as with high numbers of Ki67+CD4+ and CD8+CD28+ T cells and reduced CD95 expression by CD4+ T cells. Moreover, effective MHC-I downregulation correlated with low proportions of effector and high percentages of naïve and memory CD8+ T cells. We found that T cells infected with viruses expressing Nef alleles from the CD4low SM group expressed significantly higher levels of the CD69, interleukin (IL-2 and programmed death (PD-1 receptors than those expressing Nefs from the CD4high group. SIVsmm Nef alleles that were less active in downmodulating TCR-CD3 were also less potent in suppressing the activation of virally infected T cells and subsequent cell death. However, only nef alleles from a single animal with very low CD4+ T cell counts rendered T cells hyper-responsive to activation, similar to those of HIV-1. Our data suggest that Nef may protect the natural hosts of SIV against the loss of CD4+ T cells by at least two mechanisms: (i downmodulation of TCR-CD3 to prevent activation-induced cell death and to suppress the induction of PD-1 that may impair T cell function and survival, and (ii downmodulation of MHC-I to reduce CTL lysis of virally infected CD4+ T cells and/or bystander CD8+ T cell activation.

  12. A significant productive in vivo infection of resting cells with simian immunodeficiency virus in a macaque with AIDS.

    Science.gov (United States)

    Pahar, Bapi; Lala, Wendy; Kuebler, Dot; Liu, David

    2017-04-01

    Identifying the cells that can be infected with HIV in vivo and thus potentially persist as latent reservoirs is of high priority. Here, we report the major infected cells in a chronically simian immunodeficiency virus (SIV)-infected macaque that developed AIDS and encephalitis. A majority of the infected cells were detected as non-proliferating resting cells. SIV-infected non-proliferating resting cells were found to be playing an important role in viral pathogenesis, persistence, or reservoir formation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques.

    Science.gov (United States)

    Sugimoto, Chie; Merino, Kristen M; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A; Wakao, Hiroshi; Mori, Kazuyasu; Kim, Woong-Ki; Veazey, Ronald S; Didier, Elizabeth S; Kuroda, Marcelo J

    2017-09-01

    Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4(+) T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU(+)] CD163(+)), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants.IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model

  14. Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV.

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    Chie Sugimoto

    Full Text Available HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc, following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a

  15. Depo-provera treatment does not abrogate protection from intravenous SIV challenge in female macaques immunized with an attenuated AIDS virus.

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    Meritxell Genescà

    Full Text Available BACKGROUND: In a previous study, progesterone treatment of female monkeys immunized with live, attenuated SHIV89.6 abrogated the generally consistent protection from vaginal simian immunodeficiency virus (SIV challenge. The mechanisms responsible for the loss of protection remain to be defined. The objective of the present study was to determine whether Depo-Provera administration alters protection from intravenous SIV challenge in SHIV-immunized female macaques. METHODS AND FINDINGS: Two groups of female macaques were immunized with attenuated SHIV89.6 and then challenged intravenously with SIVmac239. Four weeks before challenge, one animal group was treated with Depo-Provera, a commonly used injectable contraceptive progestin. As expected, SHIV-immunized monkeys had significantly lower peak and set-point plasma viral RNA levels compared to naïve controls, but in contrast to previously published findings with vaginal SIV challenge, the Depo-Provera SHIV-immunized animals controlled SIV replication to a similar, or even slightly greater, degree than did the untreated SHIV-immunized animals. Control of viral replication from week 4 to week 20 after challenge was more consistent in the progesterone-treated, SHIV-immunized animals than in untreated, SHIV-immunized animals. Although levels of interferon-gamma production were similar, the SIV-specific CD8(+ T cells of progesterone-treated animals expressed more functions than the anti-viral CD8(+ T cells from untreated animals. CONCLUSIONS: Depo-Provera did not diminish the control of viral replication after intravenous SIV challenge in female macaques immunized with a live-attenuated lentivirus. This result contrasts with the previously reported effect of Depo-Provera(R on protection from vaginal SIV challenge and strongly implies that the decreased protection from vaginal challenge is due to effects of progesterone on the genital tract rather than to systemic effects. Further, these results

  16. Low dose rectal inoculation of rhesus macaques by SIV smE660 or SIVmac251 recapitulates

    Energy Technology Data Exchange (ETDEWEB)

    Hraber, Peter [Los Alamos National Laboratory; Giorgi, Elena E [Los Alamos National Laboratory; Keele, Brandon [UNIV OF ALABAMA; Li, Hui [UNIV OF ALABAMA; Learn, Gerald [UNIV OF ALABAMA

    2008-01-01

    We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA 1--5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1--5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV-macaque mucosal infection model for HIV-1 vaccine and microbicide research.

  17. Vaccine-induced virus-neutralizing antibodies and cytotoxic T cells do not protect macaques from experimental infection with simian immunodeficiency virus SIVmac32H (J5).

    NARCIS (Netherlands)

    E.G.J. Hulskotte (Ellen); A.M. Geretti (Anna Maria); C.H.J. Siebelink (Kees); G. van Amerongen (Geert); M.P. Cranage (Martin); E. Rud; S.G. Norley (Stephen); P. de Vries (Petra); A.D.M.E. Osterhaus (Albert)

    1995-01-01

    textabstractTo gain further insight into the ability of subunit vaccines to protect monkeys from experimental infection with simian immunodeficiency virus (SIV), two groups of cynomolgus macaques were immunized with either recombinant SIVmac32H-derived envelope glycoproteins (Env) incorporated into

  18. Zika virus infection.

    Science.gov (United States)

    Pougnet, Laurence; Thill, Chloé; Pougnet, Richard; Auvinet, Henri; Giacardi, Christophe; Drouillard, Isabelle

    2016-12-01

    A 21-year old woman from New-Caledonia had 40 ̊C fever with vomiting, arthralgia, myalgia, and measles-like rash. Etiological analyses showed primary infection with Zika virus. Because of severe clinical presentation, she was hospitalized in the intensive care unit of the Brest military Hospital. Zika virus is mainly transmitted by Aedes mosquitoes. If they settle in Metropolitan France, Zika virus might also spread there.

  19. Schmallenberg virus infection

    NARCIS (Netherlands)

    Wernike, K.; Elbers, A.R.W.; Beer, M.

    2015-01-01

    Since Schmallenberg virus, an orthobunyavirus of the Simbu serogroup, was identified near the German-Dutch border for the first time in late 2011 it has spread extremely quickly and caused a large epidemic in European livestock. The virus, which is transmitted by Culicoides biting midges, infects

  20. [ZIKA--VIRUS INFECTION].

    Science.gov (United States)

    Velev, V

    2016-01-01

    This review summarizes the knowledge of the scientific community for Zika-virus infection. It became popular because of severe congenital damage causes of CNS in newborns whose mothers are infected during pregnancy, as well as the risk of pandemic distribution. Discusses the peculiarities of the biology and ecology of vectors--blood-sucking mosquitoes Aedes; stages in the spread of infection and practical problems which caused during pregnancy. Attention is paid to the recommendations that allow leading national and international medical organizations to deal with the threat Zika-virus infection.

  1. Microbial Translocation and Inflammation Occur in Hyperacute Immunodeficiency Virus Infection and Compromise Host Control of Virus Replication.

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    Adam J Ericsen

    2016-12-01

    Full Text Available Within the first three weeks of human immunodeficiency virus (HIV infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS, there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood. This, heretofore unappreciated, hyperacute-phase microbial translocation was accompanied by sustained reduction of lipopolysaccharide (LPS-specific antibody titer, intestinal permeability, increased abundance of CD4+CCR5+ T cell targets of virus replication, and T cell activation. To test whether increasing gastrointestinal permeability to cause microbial translocation would amplify viremia, we treated two SIV-infected macaque 'elite controllers' with a short-course of dextran sulfate sodium (DSS-stimulating a transient increase in microbial translocation and a prolonged recrudescent viremia. Altogether, our data implicates translocating microbes as amplifiers of immunodeficiency virus replication that effectively undermine the host's capacity to contain infection.

  2. Simple Mathematical Models Do Not Accurately Predict Early SIV Dynamics

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    Cecilia Noecker

    2015-03-01

    Full Text Available Upon infection of a new host, human immunodeficiency virus (HIV replicates in the mucosal tissues and is generally undetectable in circulation for 1–2 weeks post-infection. Several interventions against HIV including vaccines and antiretroviral prophylaxis target virus replication at this earliest stage of infection. Mathematical models have been used to understand how HIV spreads from mucosal tissues systemically and what impact vaccination and/or antiretroviral prophylaxis has on viral eradication. Because predictions of such models have been rarely compared to experimental data, it remains unclear which processes included in these models are critical for predicting early HIV dynamics. Here we modified the “standard” mathematical model of HIV infection to include two populations of infected cells: cells that are actively producing the virus and cells that are transitioning into virus production mode. We evaluated the effects of several poorly known parameters on infection outcomes in this model and compared model predictions to experimental data on infection of non-human primates with variable doses of simian immunodifficiency virus (SIV. First, we found that the mode of virus production by infected cells (budding vs. bursting has a minimal impact on the early virus dynamics for a wide range of model parameters, as long as the parameters are constrained to provide the observed rate of SIV load increase in the blood of infected animals. Interestingly and in contrast with previous results, we found that the bursting mode of virus production generally results in a higher probability of viral extinction than the budding mode of virus production. Second, this mathematical model was not able to accurately describe the change in experimentally determined probability of host infection with increasing viral doses. Third and finally, the model was also unable to accurately explain the decline in the time to virus detection with increasing viral

  3. Viruses infecting marine molluscs.

    Science.gov (United States)

    Arzul, Isabelle; Corbeil, Serge; Morga, Benjamin; Renault, Tristan

    2017-07-01

    Although a wide range of viruses have been reported in marine molluscs, most of these reports rely on ultrastructural examination and few of these viruses have been fully characterized. The lack of marine mollusc cell lines restricts virus isolation capacities and subsequent characterization works. Our current knowledge is mostly restricted to viruses affecting farmed species such as oysters Crassostrea gigas, abalone Haliotis diversicolor supertexta or the scallop Chlamys farreri. Molecular approaches which are needed to identify virus affiliation have been carried out for a small number of viruses, most of them belonging to the Herpesviridae and birnaviridae families. These last years, the use of New Generation Sequencing approach has allowed increasing the number of sequenced viral genomes and has improved our capacity to investigate the diversity of viruses infecting marine molluscs. This new information has in turn allowed designing more efficient diagnostic tools. Moreover, the development of experimental infection protocols has answered some questions regarding the pathogenesis of these viruses and their interactions with their hosts. Control and management of viral diseases in molluscs mostly involve active surveillance, implementation of effective bio security measures and development of breeding programs. However factors triggering pathogen development and the life cycle and status of the viruses outside their mollusc hosts still need further investigations. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

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    Kevin R McCarthy

    Full Text Available In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm. Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac and pig-tailed macaques (SIVmne have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

  5. Swine influenza virus co-infection with Bordetella bronchiseptica enhances bacterial colonization and host immune responses exacerbating pulmonary lesions

    Science.gov (United States)

    Swine influenza virus (SIV) is one of the most important disease causing agents for the U.S. swine industry, not only as a primary pathogen but as a predisposing agent to secondary bacterial infection. Bordetella bronchiseptica (Bb) is often isolated from swine and has been shown to contribute to th...

  6. Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset

    Science.gov (United States)

    Ploquin, Mickaël J.; Casrouge, Armanda; Huot, Nicolas; Passaes, Caroline; Lécuroux, Camille; Essat, Asma; Boufassa, Faroudy; Jacquelin, Béatrice; Jochems, Simon P.; Petitjean, Gaël; Angin, Mathieu; Gärtner, Kathleen; Garcia-Tellez, Thalía; Booiman, Thijs; Boeser-Nunnink, Brigitte D.; Roques, Pierre; Saez-Cirion, Asier; Vaslin, Bruno; Dereudre-Bosquet, Nathalie; Barré-Sinoussi, Françoise; Ghislain, Mathilde; Rouzioux, Christine; Lambotte, Olivier; Albert, Matthew L.; Goujard, Cécile; Kootstra, Neeltje; Meyer, Laurence; Müller-Trutwin, Michaela C.

    2016-01-01

    Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI) were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort), as well as during controlled and uncontrolled viremia (ANRS cohorts). We also addressed IP-10 expression levels with regards to lymphoid tissues (LT) and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker) gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10. PMID:27509048

  7. Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset.

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    Mickaël J Ploquin

    2016-08-01

    Full Text Available Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort, as well as during controlled and uncontrolled viremia (ANRS cohorts. We also addressed IP-10 expression levels with regards to lymphoid tissues (LT and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.

  8. Laser Capture Microdissection Assessment of Virus Compartmentalization in the Central Nervous Systems of Macaques Infected with Neurovirulent Simian Immunodeficiency Virus

    Science.gov (United States)

    Matsuda, Kenta; Brown, Charles R.; Foley, Brian; Goeken, Robert; Whitted, Sonya; Dang, Que; Wu, Fan; Plishka, Ronald; Buckler-White, Alicia

    2013-01-01

    Nonhuman primate-simian immunodeficiency virus (SIV) models are powerful tools for studying the pathogenesis of human immunodeficiency virus type 1 (HIV-1) in the brain. Our laboratory recently isolated a neuropathogenic viral swarm, SIVsmH804E, a derivative of SIVsmE543-3, which was the result of sequential intravenous passages of viruses isolated from the brains of rhesus macaques with SIV encephalitis. Animals infected with SIVsmH804E or its precursor (SIVsmH783Br) developed SIV meningitis and/or encephalitis at high frequencies. Since we observed macaques with a combination of meningitis and encephalitis, as well as animals in which meningitis or encephalitis was the dominant component, we hypothesized that distinct mechanisms could be driving the two pathological states. Therefore, we assessed viral populations in the meninges and the brain parenchyma by laser capture microdissection. Viral RNAs were isolated from representative areas of the meninges, brain parenchyma, terminal plasma, and cerebrospinal fluid (CSF) and from the inoculum, and the SIV envelope fragment was amplified by PCR. Phylogenetic analysis of envelope sequences from the conventional progressors revealed compartmentalization of viral populations between the meninges and the parenchyma. In one of these animals, viral populations in meninges were closely related to those from CSF and shared signature truncations in the cytoplasmic domain of gp41, consistent with a common origin. Apart from magnetic resonance imaging (MRI) and positron-emission tomography (PET) imaging, CSF is the most accessible assess to the central nervous system for HIV-1-infected patients. However, our results suggest that the virus in the CSF may not always be representative of viral populations in the brain and that caution should be applied in extrapolating between the properties of viruses in these two compartments. PMID:23720733

  9. Analysis of the functional compatibility of SIV capsid sequences in the context of the FIV gag precursor.

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    César A Ovejero

    Full Text Available The formation of immature lentiviral particles is dependent on the multimerization of the Gag polyprotein at the plasma membrane of the infected cells. One key player in the virus assembly process is the capsid (CA domain of Gag, which establishes the protein-protein interactions that give rise to the hexagonal lattice of Gag molecules in the immature virion. To gain a better understanding of the functional equivalence between the CA proteins of simian and feline immunodeficiency viruses (SIV and FIV, respectively, we generated a series of chimeric FIV Gag proteins in which the CA-coding region was partially or totally replaced by its SIV counterpart. All the FIV Gag chimeras were found to be assembly-defective; however, all of them are able to interact with wild-type SIV Gag and be recruited into extracellular virus-like particles, regardless of the SIV CA sequences present in the chimeric FIV Gag. The results presented here markedly contrast with our previous findings showing that chimeric SIVs carrying FIV CA-derived sequences are assembly-competent. Overall, our data support the notion that although the SIV and FIV CA proteins share 51% amino acid sequence similarity and exhibit a similar organization, i.e., an N-terminal domain joined by a flexible linker to a C-terminal domain, their functional exchange between these different lentiviruses is strictly dependent on the context of the recipient Gag precursor.

  10. Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

    Science.gov (United States)

    Greenwood, Edward J D; Schmidt, Fabian; Kondova, Ivanela; Niphuis, Henk; Hodara, Vida L; Clissold, Leah; McLay, Kirsten; Guerra, Bernadette; Redrobe, Sharon; Giavedoni, Luis D; Lanford, Robert E; Murthy, Krishna K; Rouet, François; Heeney, Jonathan L

    2015-09-01

    The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.

  11. Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

    Directory of Open Access Journals (Sweden)

    Edward J D Greenwood

    2015-09-01

    Full Text Available The virus-host relationship in simian immunodeficiency virus (SIV infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.

  12. Real time reverse transcription (RRT)-polymerase chain reaction (PCR) methods for detection of pandemic (H1N1) 2009 influenza virus and European swine influenza A virus infections in pigs.

    Science.gov (United States)

    Slomka, Marek J; Densham, Anstice L E; Coward, Vivien J; Essen, Steve; Brookes, Sharon M; Irvine, Richard M; Spackman, Erica; Ridgeon, Jonathan; Gardner, Rebecca; Hanna, Amanda; Suarez, David L; Brown, Ian H

    2010-09-01

    There is a requirement to detect and differentiate pandemic (H1N1) 2009 (H1N1v) and established swine influenza A viruses (SIVs) by real time reverse transcription (RRT) PCR methods. First, modify an existing matrix (M) gene RRT PCR for sensitive generic detection of H1N1v and other European SIVs. Second, design an H1 RRT PCR to specifically detect H1N1v infections. RRT PCR assays were used to test laboratory isolates of SIV (n = 51; 37 European and 14 North American), H1N1v (n = 5) and avian influenza virus (AIV; n = 43). Diagnostic sensitivity and specificity were calculated for swabs (n = 133) and tissues (n = 116) collected from field cases and pigs infected experimentally with SIVs and H1N1v. The "perfect match" M gene RRT PCR was the most sensitive variant of this test for detection of established European SIVs and H1N1v. H1 RRT PCR specifically detected H1N1v but not European SIVs. Validation with clinical specimens included comparison with virus isolation (VI) as a "gold standard", while field infection with H1N1v in swine was independently confirmed by sequencing H1N1v amplified by conventional RT PCR. "Perfect match" M gene RRT PCR had 100% sensitivity and 95.2% specificity for swabs, 93.6% and 98.6% for tissues. H1 RRT PCR demonstrated sensitivity and specificity of 100% and 99.1%, respectively, for the swabs, and 100% and 100% for the tissues. Two RRT PCRs for the purposes of (i) generic detection of SIV and H1N1v infection in European pigs, and for (ii) specific detection of H1N1v (pandemic influenza) infection were validated.

  13. Quantitative Plasma Proteomic Profiling Identifies the Vitamin E Binding Protein Afamin as a Potential Pathogenic Factor in SIV Induced CNS Disease

    OpenAIRE

    Pendyala, Gurudutt; Trauger, Sunia A; Siuzdak, Gary; Fox, Howard S.

    2010-01-01

    Investigating, predicting, diagnosing and treating HIV-1-associated neurocognitive disorder (HAND) has been hindered by the lack of disease-related molecular markers. In this study, plasma from rhesus monkeys (n=6), before and after infection with simian immunodeficiency virus (SIV), was profiled to obtain differential fingerprints in protein expression during SIV-induced central nervous system (CNS) disease. A quantitative proteomic analysis was performed by means of isobaric tag for relativ...

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

    Directory of Open Access Journals (Sweden)

    Osterhaus Albert DME

    2004-11-01

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

  15. Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Fresh Lynn

    2004-07-01

    Full Text Available Abstract Background The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV in lactating rhesus macaques (Macaca mulatta as a model of natural breast milk transmission of HIV. Results Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i. and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days. Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. Conclusion These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the

  16. [Zika virus infection during pregnancy].

    Science.gov (United States)

    Picone, O; Vauloup-Fellous, C; D'Ortenzio, E; Huissoud, C; Carles, G; Benachi, A; Faye, A; Luton, D; Paty, M-C; Ayoubi, J-M; Yazdanpanah, Y; Mandelbrot, L; Matheron, S

    2016-05-01

    A Zika virus epidemic is currently ongoing in the Americas. This virus is linked to congenital infections with potential severe neurodevelopmental dysfunction. However, incidence of fetal infection and whether this virus is responsible of other fetal complications are still unknown. National and international public health authorities recommend caution and several prevention measures. Declaration of Zika virus infection is now mandatory in France. Given the available knowledge on Zika virus, we suggest here a review of the current recommendations for management of pregnancy in case of suspicious or infection by Zika virus in a pregnant woman. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Tolerance to Chronic Delta-9-Tetrahydrocannabinol (Δ9-THC) in Rhesus Macaques Infected With Simian Immunodeficiency Virus

    Science.gov (United States)

    Winsauer, Peter J.; Molina, Patricia E.; Amedee, Angela M.; Filipeanu, Catalin M.; McGoey, Robin R.; Troxclair, Dana A.; Walker, Edith M.; Birke, Leslie L.; Stouwe, Curtis Vande; Howard, Jessica M.; Leonard, Stuart T.; Moerschbaecher, Joseph M.; Lewis, Peter B.

    2011-01-01

    Although Δ9-THC has been approved to treat anorexia and weight loss associated with AIDS, it may also reduce well-being by disrupting complex behavioral processes or enhancing HIV replication. To investigate these possibilities, four groups of male rhesus macaques were trained to respond under an operant acquisition and performance procedure, and administered vehicle or Δ9-THC before and after inoculation with simian immunodeficiency virus(SIVmac251, 100 TCID50/ml, i.v.). Prior to chronic Δ9-THC and SIV inoculation, 0.032– 0.32 mg/kg of Δ9-THC produced dose-dependent rate-decreasing effects and small, sporadic error-increasing effects in the acquisition and performance components in each subject. Following 28 days of chronic Δ9-THC (0.32 mg/kg, i.m.) or vehicle twice daily, delta-9-THC-treated subjects developed tolerance to the rate-decreasing effects, and this tolerance was maintained during the initial 7–12 months irrespective of SIV infection (i.e., +THC/−SIV, +THC/+SIV). Full necropsy was performed on all SIV subjects an average of 329 days post-SIV inoculation, with postmortem histopathology suggestive of a reduced frequency of CNS pathology as well as opportunistic infections in delta-9-THC-treated subjects. Chronic Δ9-THC also significantly reduced CB-1 and CB-2 receptor levels in the hippocampus, attenuated the expression of a proinflammatory cytokine (MCP-1), and did not increase viral load in plasma, cerebrospinal fluid, or brain tissue compared to vehicle-treated subjects with SIV. Together, these data indicate that chronic Δ9-THC produces tolerance to its behaviorally disruptive effects on complex tasks while not adversely affecting viral load or other markers of disease progression during the early stages of infection. PMID:21463073

  18. An "escape clock" for estimating the turnover of SIV DNA in resting CD4⁺ T cells.

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    Jeanette Reece

    Full Text Available Persistence of HIV DNA presents a major barrier to the complete control of HIV infection under current therapies. Most studies suggest that cells with latently integrated HIV decay very slowly under therapy. However, it is much more difficult to study the turnover and persistence of HIV DNA during active infection. We have developed an "escape clock" approach for measuring the turnover of HIV DNA in resting CD4+ T cells. This approach studies the replacement of wild-type (WT SIV DNA present in early infection by CTL escape mutant (EM strains during later infection. Using a strain-specific real time PCR assay, we quantified the relative amounts of WT and EM strains in plasma SIV RNA and cellular SIV DNA. Thus we can track the formation and turnover of SIV DNA in sorted resting CD4+ T cells. We studied serial plasma and PBMC samples from 20 SIV-infected Mane-A*10 positive pigtail macaques that have a signature Gag CTL escape mutation. In animals with low viral load, WT virus laid down early in infection is extremely stable, and the decay of this WT species is very slow, consistent with findings in subjects on anti-retroviral medications. However, during active, high level infection, most SIV DNA in resting cells was turning over rapidly, suggesting a large pool of short-lived DNA produced by recent infection events. Our results suggest that, in order to reduce the formation of a stable population of SIV DNA, it will be important either to intervene very early or intervene during active replication.

  19. Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine

    Science.gov (United States)

    Jensen, Kara; dela Pena-Ponce, Myra Grace; Piatak, Michael; Shoemaker, Rebecca; Oswald, Kelli; Jacobs, William R.; Fennelly, Glenn; Lucero, Carissa; Mollan, Katie R.; Hudgens, Michael G.; Amedee, Angela; Kozlowski, Pamela A.; Estes, Jacob D.; Lifson, Jeffrey D.; Van Rompay, Koen K. A.; Larsen, Michelle

    2016-01-01

    ABSTRACT Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants. PMID:27655885

  20. Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine.

    Science.gov (United States)

    Jensen, Kara; Dela Pena-Ponce, Myra Grace; Piatak, Michael; Shoemaker, Rebecca; Oswald, Kelli; Jacobs, William R; Fennelly, Glenn; Lucero, Carissa; Mollan, Katie R; Hudgens, Michael G; Amedee, Angela; Kozlowski, Pamela A; Estes, Jacob D; Lifson, Jeffrey D; Van Rompay, Koen K A; Larsen, Michelle; De Paris, Kristina

    2017-01-01

    Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants. Copyright © 2017 American Society for Microbiology.

  1. Zika virus infection

    DEFF Research Database (Denmark)

    Nazerai, Loulieta; Scholler, Amalie Skak; Buus, Soren

    2017-01-01

    Zika virus (ZIKV) is a mosquito-borne flavivirus that has drawn worldwide attention due to its association to neurologic complications, particularly severe congenital malformations. While ZIKV can replicate efficiently and cause disease in human hosts, it fails to replicate to substantial titers...... mice by introducing the virus directly in the brain via intracerebral (i.c.) inoculation. In this way, the antigen is precisely placed at the site of interest, evading the first line of defense, and thus rendering the mice susceptible to infection. We found that, while intravenous (i.v.) inoculation...... of two different strains of WT mice with low doses of ZIKV does not result in viremia, it is nevertheless able to induce both cell-mediated and humoral immunity as well as clinical protection against subsequent i.c challenge with lethal doses of the virus. In order to determine the contribution of key...

  2. Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2.

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    Bin Jia

    2009-05-01

    Full Text Available Tetherin, also known as BST2, CD317 or HM1.24, was recently identified as an interferon-inducible host-cell factor that interferes with the detachment of virus particles from infected cells. HIV-1 overcomes this restriction by expressing an accessory protein, Vpu, which counteracts tetherin. Since lentiviruses of the SIV(smm/mac/HIV-2 lineage do not have a vpu gene, this activity has likely been assumed by other viral gene products. We found that deletion of the SIV(mac239 nef gene significantly impaired virus release in cells expressing rhesus macaque tetherin. Virus release could be restored by expressing Nef in trans. However, Nef was unable to facilitate virus release in the presence of human tetherin. Conversely, Vpu enhanced virus release in the presence of human tetherin, but not in the presence of rhesus tetherin. In accordance with the species-specificity of Nef in mediating virus release, SIV Nef downregulated cell-surface expression of rhesus tetherin, but did not downregulate human tetherin. The specificity of SIV Nef for rhesus tetherin mapped to four amino acids in the cytoplasmic domain of the molecule that are missing from human tetherin, whereas the specificity of Vpu for human tetherin mapped to amino acid differences in the transmembrane domain. Nef alleles of SIV(smm, HIV-2 and HIV-1 were also able to rescue virus release in the presence of both rhesus macaque and sooty mangabey tetherin, but were generally ineffective against human tetherin. Thus, the ability of Nef to antagonize tetherin from these Old World primates appears to be conserved among the primate lentiviruses. These results identify Nef as the viral gene product of SIV that opposes restriction by tetherin in rhesus macaques and sooty mangabeys, and reveal species-specificity in the activities of both Nef and Vpu in overcoming tetherin in their respective hosts.

  3. Comparative characterization of transfection- and infection-derived simian immunodeficiency virus challenge stocks for in vivo nonhuman primate studies.

    Science.gov (United States)

    Del Prete, Gregory Q; Scarlotta, Matthew; Newman, Laura; Reid, Carolyn; Parodi, Laura M; Roser, James D; Oswald, Kelli; Marx, Preston A; Miller, Christopher J; Desrosiers, Ronald C; Barouch, Dan H; Pal, Ranajit; Piatak, Michael; Chertova, Elena; Giavedoni, Luis D; O'Connor, David H; Lifson, Jeffrey D; Keele, Brandon F

    2013-04-01

    Simian immunodeficiency virus (SIV) stocks for in vivo nonhuman primate models of AIDS are typically generated by transfection of 293T cells with molecularly cloned viral genomes or by expansion in productively infected T cells. Although titers of stocks are determined for infectivity in vitro prior to in vivo inoculation, virus production methods may differentially affect stock features that are not routinely analyzed but may impact in vivo infectivity, mucosal transmissibility, and early infection events. We performed a detailed analysis of nine SIV stocks, comprising five infection-derived SIVmac251 viral swarm stocks and paired infection- and transfected-293T-cell-derived stocks of both SIVmac239 and SIVmac766. Representative stocks were evaluated for (i) virus content, (ii) infectious titer, (iii) sequence diversity and polymorphism frequency by single-genome amplification and 454 pyrosequencing, (iv) virion-associated Env content, and (v) cytokine and chemokine content by 36-plex Luminex analysis. Regardless of production method, all stocks had comparable particle/infectivity ratios, with the transfected-293T stocks possessing the highest overall virus content and infectivity titers despite containing markedly lower levels of virion-associated Env than infection-derived viruses. Transfected-293T stocks also contained fewer and lower levels of cytokines and chemokines than infection-derived stocks, which had elevated levels of multiple analytes, with substantial variability among stocks. Sequencing of the infection-derived SIVmac251 stocks revealed variable levels of viral diversity between stocks, with evidence of stock-specific selection and expansion of unique viral lineages. These analyses suggest that there may be underappreciated features of SIV in vivo challenge stocks with the potential to impact early infection events, which may merit consideration when selecting virus stocks for in vivo studies.

  4. Pregnancy outcome and clinical status of gilts following experimental infection by H1N2, H3N2 and H1N1pdm09 influenza A viruses during the last month of gestation.

    Science.gov (United States)

    Kwit, Krzysztof; Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona

    2015-10-01

    The present study was planned to study the effect of various subtypes of swine influenza virus (SIV) circulating among pigs (H1N2, H3N2 and emerging pandemic strain of H1N1 influenza A virus (H1N1pdm09) on the course of pregnancy in naïve gilts experimentally infected during the last month of pregnancy. In addition, the clinical course of infection, distribution of viruses in various tissues (blood, placenta, fetal lung), and selected immunological, reproductive and productive parameters were also investigated. All SIV-inoculated gilts became infected. No abortions, stillbirths, intrauterine deaths or mummified fetuses were observed. No clinical signs of influenza virus infection or other disorders were observed in piglets born from infected and control gilts. There was a significant decrease in the number and frequency of lymphocytes in gilts inoculated with all influenza viruses. In general, the concentrations of IL-6, IL-10 and TNF-α were significantly higher in SIV-inoculated gilts as than in control animals, while IL-4 and IFN-γ were not detected in plasma at any time post-inoculation in SIV- or mock-inoculated gilts. No evidence for transplacental transmission of SIV was found. Viremia was also not observed in any of the infected females. On the basis of recent results, we hypothesize that pregnancy failure observed during SIV infection under field conditions is probably related to high fever and pro-inflammatory cytokines rather than a direct effect of the virus on the placenta, embryo or fetus.

  5. Post-exposure prophylaxis for SIV revisited: Animal model for HIV prevention

    Directory of Open Access Journals (Sweden)

    Bekele Girma

    2006-11-01

    Full Text Available Abstract Background A 4-week, uninterrupted treatment with 9-(2-phosphonyl-methoxypropylyadenine (PMPA, commonly called tenofovir completely prevents simian immunodeficiency virus (SIVmne infection in cynomolgus macaques if treatment begins within 24 hours after SIVmne inoculation, but is less effective if treatment is delayed or duration of treatment is shortened. Critical factors for efficacy include timing and duration of treatment, potency of antiretroviral drug and a contribution from antiviral immune responses. Therefore, we evaluated the impact of one or more treatment interruptions plus SIVmne re-exposures on efficacy of PMPA treatment to prevent SIVmne infection in cynomolgus macaques. We also evaluated whether macaques with pre-existing SIV immune responses show increased efficacy of treatment. Eight PMPA-treated, virus-negative and seronegative macaques, and five PMPA-treated, virus-negative but weakly or strongly seropositive macaques were re-inoculated with SIVmne and treated with PMPA starting 24 hr post inoculation. Thereafter, they received either a 5-week treatment involving one interruption plus one SIVmne challenge or a 10-week treatment involving six interruptions plus six SIVmne challenges early during treatment. Parameters measured were plasma SIV RNA, SIV-antibody response, CD4+ T lymphocyte subsets and in vivo CD8+ cell-suppression of virus infection. Results All seronegative macaques developed persistent antibody response beginning 4 to 8 weeks after stopping PMPA-treatment in absence of viremia in a majority of macaques and coinciding with onset of intermittent viremia in other macaques. In contrast, all weakly or strongly seropositive macaques showed immediate increase in titers (> 1600 of SIV antibodies, even before the end of PMPA-treatment, and in absence of detectable viremia. However, in vivo CD8+ -cell depletion revealed CD8 cell-suppression of viremia and persistence of virus in the macaques as long as 2 years

  6. Recombinant vaccinia DIs expressing simian immunodeficiency virus gag and pol in mammalian cells induces efficient cellular immunity as a safe immunodeficiency virus vaccine candidate.

    Science.gov (United States)

    Okamura, Tomotaka; Someya, Kenji; Matsuo, Kazuhiro; Hasegawa, Atsuhiko; Yamamoto, Naoki; Honda, Mitsuo

    2006-01-01

    A highly attenuated vaccinia virus substrain of Dairen-I (DIs) shows promise as a candidate vector for eliciting positive immunity against immune deficiency virus. DIs was randomly obtained by serial 1-day egg passages of a chorioarantoic membrane-adapted Dairen strain (DIE), resulting in substantial genomic deletion, including various genes regulating the virus-host-range. To investigate the impact of that deletion and of the subsequent insertion of a foreign gene into that region of DIs on the ability of the DIs recombinant to induce antigen-specific immunity, we generated a recombinant vaccinia DIs expressing fulllength gag and pol genes of simian immunodeficiency virus (SIV) (rDIsSIV gag/pol) and studied the biological and immunological characteristics of the recombinant natural mutant. The rDIsSIV gag/pol developed a tiny plaque on the chick embryo fibroblast (CEF). Viral particles of rDIsSIV gag/pol as well as SIV Gag-like particles were electromicroscopically detected in the cytoplasm. Interestingly, the recombinant DIs strain grows well in CEF cells but not in mammalian cells. While rDIsSIV gag/pol produces SIV proteins in mammalian HeLa and CV-1 cells, recombinant modified vaccinia Ankara strain (MVA) expressing SIV gag and pol genes (MVA/SIV239 gag/pol) clearly replicates in HeLa and CV-1 cell lines under synchronized growth conditions and produces the SIV protein in all cell lines. Moreover, intradermal administration of rDIsSIV gag/pol or of MVA/SIV239 gag/pol elicited similar levels of IFN-gamma spot-forming cells specific for SIV Gag. If the non-productive infection characteristically induced by recombinant DIs is sufficient to trigger immune induction, as we believe it is, then a human immunodeficiency virus vaccine employing the DIs recombinant would have the twin advantages of being both effective and safe.

  7. 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 ...

  8. Measuring turnover of SIV DNA in resting CD4+ T cells using pyrosequencing: implications for the timing of HIV eradication therapies.

    Directory of Open Access Journals (Sweden)

    Jeanette C Reece

    Full Text Available Resting CD4+ T cells are a reservoir of latent HIV-1. Understanding the turnover of HIV DNA in these cells has implications for the development of eradication strategies. Most studies of viral latency focus on viral persistence under antiretroviral therapy (ART. We studied the turnover of SIV DNA resting CD4+ T cells during active infection in a cohort of 20 SIV-infected pigtail macaques. We compared SIV sequences at two Mane-A1*084:01-restricted CTL epitopes using serial plasma RNA and resting CD4+ T cell DNA samples by pyrosequencing, and used a mathematical modeling approach to estimate SIV DNA turnover. We found SIV DNA turnover in resting CD4+ T cells was slow in animals with low chronic viral loads, consistent with the long persistence of latency seen under ART. However, in animals with high levels of chronic viral replication, turnover was high. SIV DNA half-life within resting CD4 cells correleated with viral load (p = 0.0052 at the Gag KP9 CTL epitope. At a second CTL epitope in Tat (KVA10 there was a trend towards an association of SIV DNA half-life in resting CD4 cells and viral load (p = 0.0971. Further, we found that the turnover of resting CD4+ T cell SIV DNA was higher for escape during early infection than for escape later in infection (p = 0.0084. Our results suggest viral DNA within resting CD4 T cells is more labile and may be more susceptible to reactivation/eradication treatments when there are higher levels of virus replication and during early/acute infection.

  9. Form follows function: astrocyte morphology and immune dysfunction in SIV neuroAIDS.

    Science.gov (United States)

    Lee, Kim M; Chiu, Kevin B; Renner, Nicole A; Sansing, Hope A; Didier, Peter J; MacLean, Andrew G

    2014-10-01

    Cortical function is disrupted in neuroinflammatory disorders, including HIV-associated neurocognitive disorders (HAND). Astrocyte dysfunction includes retraction of foot processes from the blood-brain barrier and decreased removal of neurotransmitters from synaptic clefts. Mechanisms of astrocyte activation, including innate immune function and the fine neuroanatomy of astrocytes, however, remain to be investigated. We quantified the number of glial fibrillary acidic protein (GFAP)-labeled astrocytes per square millimeter and the proportion of astrocytes immunopositive for Toll-like receptor 2 (TLR2) to examine innate immune activation in astrocytes. We also performed detailed morphometric analyses of gray and white matter astrocytes in the frontal and parietal lobes of rhesus macaques infected with simian immunodeficiency virus (SIV), both with and without encephalitis, an established model of AIDS neuropathogenesis. Protoplasmic astrocytes (gray matter) and fibrous astrocytes (deep white matter) were imaged, and morphometric features were analyzed using Neurolucida. Gray matter and white matter astrocytes showed no change in cell body size in animals infected with SIV regardless of encephalitic status. In SIV-infected macaques, both gray and white matter astrocytes had shorter, less ramified processes, resulting in decreased cell arbor compared with controls. SIV-infected macaques with encephalitis showed decreases in arbor length in white matter astrocytes and reduced complexity in gray matter astrocytes compared to controls. These results provide the first evidence that innate immune activation of astrocytes is linked to altered cortical astrocyte morphology in SIV/HIV infection. Here, we demonstrate that astrocyte remodeling is correlated with infection. Perturbed neuron-glia signaling may be a driving factor in the development of HAND.

  10. Linking pig-tailed macaque major histocompatibility complex class I haplotypes and cytotoxic T lymphocyte escape mutations in simian immunodeficiency virus infection.

    Science.gov (United States)

    Gooneratne, Shayarana L; Alinejad-Rokny, Hamid; Ebrahimi, Diako; Bohn, Patrick S; Wiseman, Roger W; O'Connor, David H; Davenport, Miles P; Kent, Stephen J

    2014-12-01

    The influence of major histocompatibility complex class I (MHC-I) alleles on human immunodeficiency virus (HIV) diversity in humans has been well characterized at the population level. MHC-I alleles likely affect viral diversity in the simian immunodeficiency virus (SIV)-infected pig-tailed macaque (Macaca nemestrina) model, but this is poorly characterized. We studied the evolution of SIV in pig-tailed macaques with a range of MHC-I haplotypes. SIV(mac251) genomes were amplified from the plasma of 44 pig-tailed macaques infected with SIV(mac251) at 4 to 10 months after infection and characterized by Illumina deep sequencing. MHC-I typing was performed on cellular RNA using Roche/454 pyrosequencing. MHC-I haplotypes and viral sequence polymorphisms at both individual mutations and groups of mutations spanning 10-amino-acid segments were linked using in-house bioinformatics pipelines, since cytotoxic T lymphocyte (CTL) escape can occur at different amino acids within the same epitope in different animals. The approach successfully identified 6 known CTL escape mutations within 3 Mane-A1*084-restricted epitopes. The approach also identified over 70 new SIV polymorphisms linked to a variety of MHC-I haplotypes. Using functional CD8 T cell assays, we confirmed that one of these associations, a Mane-B028 haplotype-linked mutation in Nef, corresponded to a CTL epitope. We also identified mutations associated with the Mane-B017 haplotype that were previously described to be CTL epitopes restricted by Mamu-B*017:01 in rhesus macaques. This detailed study of pig-tailed macaque MHC-I genetics and SIV polymorphisms will enable a refined level of analysis for future vaccine design and strategies for treatment of HIV infection. Cytotoxic T lymphocytes select for virus escape mutants of HIV and SIV, and this limits the effectiveness of vaccines and immunotherapies against these viruses. Patterns of immune escape variants are similar in HIV type 1-infected human subjects that

  11. Viruses infecting maize

    OpenAIRE

    Krstić, Branka; Stanković, Ivana; Bulajić, Aleksandra

    2014-01-01

    Over 40 plant viruses has been known to cause diseases of maize, but economically the most important yield looses, which in certain years can be total, are caused by viruses from Potyvirus genera, known to be aphid-transmitted in a non-persistant maner. The most important viruses, pathogens of maize, sugar cane and sorghum are considered to be Maize dwarf mosaic virus (MDMV), Sorghum mosaic virus (SrMV), Sugarcane mosaic virus (SCMV), and Johnsongrass mosaic virus (JGMV). In Serbia, the prese...

  12. Live attenuated rubella vectors expressing SIV and HIV vaccine antigens replicate and elicit durable immune responses in rhesus macaques

    Science.gov (United States)

    2013-01-01

    Background Live attenuated viruses are among our most potent and effective vaccines. For human immunodeficiency virus, however, a live attenuated strain could present substantial safety concerns. We have used the live attenuated rubella vaccine strain RA27/3 as a vector to express SIV and HIV vaccine antigens because its safety and immunogenicity have been demonstrated in millions of children. One dose protects for life against rubella infection. In previous studies, rubella vectors replicated to high titers in cell culture while stably expressing SIV and HIV antigens. Their viability in vivo, however, as well as immunogenicity and antibody persistence, were unknown. Results This paper reports the first successful trial of rubella vectors in rhesus macaques, in combination with DNA vaccines in a prime and boost strategy. The vectors grew robustly in vivo, and the protein inserts were highly immunogenic. Antibody titers elicited by the SIV Gag vector were greater than or equal to those elicited by natural SIV infection. The antibodies were long lasting, and they were boosted by a second dose of replication-competent rubella vectors given six months later, indicating the induction of memory B cells. Conclusions Rubella vectors can serve as a vaccine platform for safe delivery and expression of SIV and HIV antigens. By presenting these antigens in the context of an acute infection, at a high level and for a prolonged duration, these vectors can stimulate a strong and persistent immune response, including maturation of memory B cells. Rhesus macaques will provide an ideal animal model for demonstrating immunogenicity of novel vectors and protection against SIV or SHIV challenge. PMID:24041113

  13. Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers.

    Directory of Open Access Journals (Sweden)

    Benjamin B Policicchio

    2016-09-01

    Full Text Available Viruses that persist despite seemingly effective antiretroviral treatment (ART and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the "shock and kill" strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35-50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml peaking at 5-12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control

  14. The levels of DNGR-1 and its ligand-bearing cells were altered after human and simian immunodeficiency virus infection.

    Science.gov (United States)

    Yao, Wen-Rong; Li, Dong; Yu, Lei; Wang, Feng-Jie; Xing, Hui; Yang, Gui-Bo

    2017-08-01

    Dendritic cell NK lectin Group Receptor-1 (DNGR-1), also known as C-type lectin domain family 9, member A (CLEC9A), is a member of C-type lectin receptor superfamily expressed primarily on dendritic cells (DC) that excel in cross-presentation of exogenous antigens. To find out whether and how it is affected in human immunodeficiency virus infections or acquired immunodeficiency syndromes (HIV/AIDS), DNGR-1 expression and DNGR-1-binding cells in simian/human immunodeficiency virus (SHIV) and simian immunodeficiency virus (SIV)-infected rhesus macaques and antiretroviral therapy (ART)-treated AIDS patients were examined by real-time RT-PCR, flow cytometry, and confocal microscopy. DNGR-1 expression was observed in both lymphoid and non-lymphoid tissues including gut-associated lymphoid tissues (GALT) of rhesus macaques. DNGR-1 mRNA levels were significantly reduced in the blood while significantly elevated in the GALT of SHIV/SIV-infected rhesus macaques. DNGR-1 transcription levels were also significantly reduced in the blood of ART-treated AIDS patients irrespective of viral status. White blood cells with exposed DNGR-1 ligands were significantly increased in ART-treated AIDS patients, while significantly decreased in SIV-infected rhesus macaques. These data indicate that DNGR-1 expression, and by extension, the function of cross-presentation of antigens associated with dead/damaged cells might be compromised in HIV/SIV infection, which might play a role in HIV/AIDS pathogenesis and should be taken into consideration in therapeutic AIDS vaccine development.

  15. Comparison of protection from homologous cell-free vs cell-associated SIV challenge afforded by inactivated whole SIV vaccines.

    NARCIS (Netherlands)

    J.L. Heeney (Jonathan); P. de Vries (Petra); R. Dubbes (Rob); W. Koornstra (Willem); H. Niphuis; P. ten Haaft (Peter); J. Boes (Jolande); M.E.M. Dings (Marlinda); B. Morein (Bror); A.D.M.E. Osterhaus (Albert)

    1992-01-01

    textabstractThis study attempted to determine if SIV vaccines could protect against challenge with peripheral blood mononuclear cells (PBMCs) from an SIV infected rhesus monkey. Mature Macaca mulatta were vaccinated four times with formalin inactivated SIVmac32H administered in MDP adjuvant (n = 8)

  16. Mucosal vaccination with heterologous viral vectored vaccine targeting subdominant SIV accessory antigens strongly inhibits early viral replication

    DEFF Research Database (Denmark)

    Xu, Huanbin; Andersson, Anne-Marie Carola; Ragonnaud, Emeline

    2017-01-01

    Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat...... immune hyperactivation as measured by naïve T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected...... animals of unknown long-term significance. In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia....

  17. Vaccination and timing influence SIV immune escape viral dynamics in vivo.

    Directory of Open Access Journals (Sweden)

    Liyen Loh

    2008-01-01

    Full Text Available CD8+ cytotoxic T lymphocytes (CTL can be effective at controlling HIV-1 in humans and SIV in macaques, but their utility is partly offset by mutational escape. The kinetics of CTL escape and reversion of escape mutant viruses upon transmission to MHC-mismatched hosts can help us understand CTL-mediated viral control and the fitness cost extracted by immune escape mutation. Traditional methods for following CTL escape and reversion are, however, insensitive to minor viral quasispecies. We developed sensitive quantitative real-time PCR assays to track the viral load of SIV Gag164-172 KP9 wild-type (WT and escape mutant (EM variants in pigtail macaques. Rapid outgrowth of EM virus occurs during the first few weeks of infection. However, the rate of escape plateaued soon after, revealing a prolonged persistence of WT viremia not detectable by standard cloning and sequencing methods. The rate of escape of KP9 correlated with levels of vaccine-primed KP9-specific CD8+ T cells present at that time. Similarly, when non-KP9 responder (lacking the restricting Mane-A*10 allele macaques were infected with SHIVmn229 stock containing a mixture of EM and WT virus, rapid reversion to WT was observed over the first 2 weeks following infection. However, the rate of reversion to WT slowed dramatically over the first month of infection. The serial quantitation of escape mutant viruses evolving during SIV infection shows that rapid dynamics of immune escape and reversion can be observed in early infection, particularly when CD8 T cells are primed by vaccination. However, these early rapid rates of escape and reversion are transient and followed by a significant slowing in these rates later during infection, highlighting that the rate of escape is significantly influenced by the timing of its occurrence.

  18. Primary simian immunodeficiency virus SIVmnd-2 infection in mandrills (Mandrillus sphinx).

    Science.gov (United States)

    Onanga, Richard; Souquière, Sandrine; Makuwa, Maria; Mouinga-Ondeme, Augustin; Simon, François; Apetrei, Cristian; Roques, Pierre

    2006-04-01

    Mandrills are the only nonhuman primate (NHP) naturally infected by two types of simian immunodeficiency virus (SIV): SIVmnd-1 and SIVmnd-2. We have already reported that the high SIVmnd-1 replication during primary infection contrasts with only transient changes in CD4+ and CD8+ cell counts. Since early virus-host interactions predict viral control and disease progression in human immunodeficiency virus-infected patients, we investigated the dynamics of SIVmnd-2 primary infection in mandrills to examine the impact on immune effectors in blood and lymph nodes (LNs). To avoid in vitro strain selection, all mandrills in this study received plasma from SIVmnd-2-infected mandrills. SIVmnd-2 plasma viremia peaked at 10(7) to 10(8) RNA copies/ml between days 7 and 10. This peak was followed in all four monkeys by a decline in virus replication, with a set point level of 10(5) to 10(6) RNA copies/ml at day 42 postinfection (p.i.). Viral DNA load in PBMC and LNs also peaked between days 7 and 10 (10(5) to 10(6) DNA copies/10(6) cells) and stabilized at 10(3) to 10(4) DNA copies/10(6) cells during the chronic phase. Anti-SIVmnd-2 antibodies were detected starting from days 28 to 32. A transitory decline of CD3+ CD4+ cells in the LNs occurred in animals with high peak VLs. CD4+ and CD8+ T-cell activation in blood and LNs was noted between days 5 and 17 p.i., surrounding the peak of viral replication. This was most significant in the LNs. Activation markers then returned to preinfection values despite continuous and active viral replication during the chronic infection. The dynamics of SIVmnd-2 infection in mandrills showed a pattern similar to that of SIVmnd-1 infection. This might be a general feature of nonpathogenic SIV natural African NHP models.

  19. Lymphocyte-Dominant Encephalitis and Meningitis in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.

    Science.gov (United States)

    Mangus, Lisa M; Beck, Sarah E; Queen, Suzanne E; Brill, Samuel A; Shirk, Erin N; Metcalf Pate, Kelly A; Muth, Dillon C; Adams, Robert J; Gama, Lucio; Clements, Janice E; Mankowski, Joseph L

    2018-01-01

    A retrospective neuropathologic review of 30 SIV-infected pigtailed macaques receiving combination antiretroviral therapy (cART) was conducted. Seventeen animals with lymphocyte-dominant inflammation in the brain and/or meninges that clearly was morphologically distinct from prototypic SIV encephalitis and human immunodeficiency virus encephalitis were identified. Central nervous system (CNS) infiltrates in cART-treated macaques primarily comprised CD20+ B cells and CD3+ T cells with fewer CD68+ macrophages. Inflammation was associated with low levels of SIV RNA in the brain as shown by in situ hybridization, and generally was observed in animals with episodes of cerebrospinal fluid (CSF) viral rebound or sustained plasma and CSF viremia during treatment. Although the lymphocytic CNS inflammation in these macaques shared morphologic characteristics with uncommon immune-mediated neurologic disorders reported in treated HIV patients, including CNS immune reconstitution inflammatory syndrome and neurosymptomatic CSF escape, the high prevalence of CNS lesions in macaques suggests that persistent adaptive immune responses in the CNS also may develop in neuroasymptomatic or mildly impaired HIV patients yet remain unrecognized given the lack of access to CNS tissue for histopathologic evaluation. Continued investigation into the mechanisms and outcomes of CNS inflammation in cART-treated, SIV-infected macaques will advance our understanding of the consequences of residual CNS HIV replication in patients on cART, including the possible contribution of adaptive immune responses to HIV-associated neurocognitive disorders. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Genetic subspecies diversity of the chimpanzee CD4 virus-receptor gene

    DEFF Research Database (Denmark)

    Hvilsom, Christina; Carlsen, Frands; Siegismund, Hans R

    2008-01-01

    Chimpanzees are naturally and asymptomatically infected by simian immunodeficiency virus (SIV). Pathogenic properties of SIV/HIV vary and differences in susceptibility and pathogenicity of SIV/HIV depend in part on host-specific factors such as virus-receptor/co-receptor interactions. Since CD4...... plays a primary role in virus binding and since SIVcpz have been found only in two African chimpanzee subspecies, we characterized the genetic diversity of CD4 receptors in all four recognized subspecies of chimpanzees. We found noticeable variation in the first variable region V1 of CD4 and in intron...

  1. 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 ...

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

    Directory of Open Access Journals (Sweden)

    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

  3. Early myeloid dendritic cell dysregulation is predictive of disease progression in simian immunodeficiency virus infection.

    Directory of Open Access Journals (Sweden)

    Viskam Wijewardana

    2010-12-01

    Full Text Available Myeloid dendritic cells (mDC are lost from blood in individuals with human immunodeficiency virus (HIV infection but the mechanism for this loss and its relationship to disease progression are not known. We studied the mDC response in blood and lymph nodes of simian immunodeficiency virus (SIV-infected rhesus macaques with different disease outcomes. Early changes in blood mDC number were inversely correlated with virus load and reflective of eventual disease outcome, as animals with stable infection that remained disease-free for more than one year had average increases in blood mDC of 200% over preinfection levels at virus set-point, whereas animals that progressed rapidly to AIDS had significant loss of mDC at this time. Short term antiretroviral therapy (ART transiently reversed mDC loss in progressor animals, whereas discontinuation of ART resulted in a 3.5-fold increase in mDC over preinfection levels only in stable animals, approaching 10-fold in some cases. Progressive SIV infection was associated with increased CCR7 expression on blood mDC and an 8-fold increase in expression of CCL19 mRNA in lymph nodes, consistent with increased mDC recruitment. Paradoxically, lymph node mDC did not accumulate in progressive infection but rather died from caspase-8-dependent apoptosis that was reduced by ART, indicating that increased recruitment is offset by increased death. Lymph node mDC from both stable and progressor animals remained responsive to exogenous stimulation with a TLR7/8 agonist. These data suggest that mDC are mobilized in SIV infection but that an increase in the CCR7-CCL19 chemokine axis associated with high virus burden in progressive infection promotes exodus of activated mDC from blood into lymph nodes where they die from apoptosis. We suggest that inflamed lymph nodes serve as a sink for mDC through recruitment, activation and death that contributes to AIDS pathogenesis.

  4. Detection and Partial Characterization of Simian Immunodeficiency Virus SIVsm Strains from Bush Meat Samples from Rural Sierra Leone

    OpenAIRE

    Apetrei, Cristian; Metzger, Michael J.; Richardson, David; Ling, Binhua; Telfer, Paul T.; Reed, Patricia; Robertson, David L.; Marx, Preston A.

    2005-01-01

    Human immunodeficiency virus type 2 (HIV-2) originated from simian immunodeficiency viruses (SIVs) that naturally infect sooty mangabeys (SMs; Cercocebus atys). In order to further investigate the relationship between HIV-2 and SIVsm, the SIV specific to the SM, we characterized seven new SIVsm strains from SMs sold in Sierra Leone markets as bush meat. The gag, pol, and env sequences showed that, while the viruses of all seven SMs belonged to the SIVsm-HIV-2 lineage, they were highly diverge...

  5. Association of activating KIR copy number variation of NK cells with containment of SIV replication in rhesus monkeys.

    Directory of Open Access Journals (Sweden)

    Ina Hellmann

    2011-12-01

    Full Text Available While the contribution of CD8⁺ cytotoxic T lymphocytes to early containment of HIV-1 spread is well established, a role for NK cells in controlling HIV-1 replication during primary infection has been uncertain. The highly polymorphic family of KIR molecules expressed on NK cells can inhibit or activate these effector cells and might therefore modulate their activity against HIV-1-infected cells. In the present study, we investigated copy number variation in KIR3DH loci encoding the only activating KIR receptor family in rhesus monkeys and its effect on simian immunodeficiency virus (SIV replication during primary infection in rhesus monkeys. We observed an association between copy numbers of KIR3DH genes and control of SIV replication in Mamu-A*01⁻ rhesus monkeys that express restrictive TRIM5 alleles. These findings provide further evidence for an association between NK cells and the early containment of SIV replication, and underscore the potential importance of activating KIRs in stimulating NK cell responses to control SIV spread.

  6. Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers.

    Science.gov (United States)

    Policicchio, Benjamin B; Xu, Cuiling; Brocca-Cofano, Egidio; Raehtz, Kevin D; He, Tianyu; Ma, Dongzhu; Li, Hui; Sivanandham, Ranjit; Haret-Richter, George S; Dunsmore, Tammy; Trichel, Anita; Mellors, John W; Hahn, Beatrice H; Shaw, George M; Ribeiro, Ruy M; Pandrea, Ivona; Apetrei, Cristian

    2016-09-01

    Viruses that persist despite seemingly effective antiretroviral treatment (ART) and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the "shock and kill" strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis)] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD) to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35-50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml) peaking at 5-12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml) that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control. Comparison of the

  7. Autophagy in Measles Virus Infection

    Directory of Open Access Journals (Sweden)

    Aurore Rozières

    2017-11-01

    Full Text Available Autophagy is a biological process that helps cells to recycle obsolete cellular components and which greatly contributes to maintaining cellular integrity in response to environmental stress factors. Autophagy is also among the first lines of cellular defense against invading microorganisms, including viruses. The autophagic destruction of invading pathogens, a process referred to as xenophagy, involves cytosolic autophagy receptors, such as p62/SQSTM1 (Sequestosome 1 or NDP52/CALCOCO2 (Nuclear Dot 52 KDa Protein/Calcium Binding And Coiled-Coil Domain 2, which bind to microbial components and target them towards growing autophagosomes for degradation. However, most, if not all, infectious viruses have evolved molecular tricks to escape from xenophagy. Many viruses even use autophagy, part of the autophagy pathway or some autophagy-associated proteins, to improve their infectious potential. In this regard, the measles virus, responsible for epidemic measles, has a unique interface with autophagy as the virus can induce multiple rounds of autophagy in the course of infection. These successive waves of autophagy result from distinct molecular pathways and seem associated with anti- and/or pro-measles virus consequences. In this review, we describe what the autophagy–measles virus interplay has taught us about both the biology of the virus and the mechanistic orchestration of autophagy.

  8. Dengue virus antibodies enhance Zika virus infection.

    Science.gov (United States)

    Paul, Lauren M; Carlin, Eric R; Jenkins, Meagan M; Tan, Amanda L; Barcellona, Carolyn M; Nicholson, Cindo O; Michael, Scott F; Isern, Sharon

    2016-12-01

    For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection. Our results suggest that pre-existing DENV immunity may enhance ZIKV infection in vivo and may lead to increased disease severity. Understanding the interplay between ZIKV and DENV will be critical in informing public health responses and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.

  9. Hepatitis Virus Infections in Poultry.

    Science.gov (United States)

    Yugo, Danielle M; Hauck, Ruediger; Shivaprasad, H L; Meng, Xiang-Jin

    2016-09-01

    Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families including avian hepatitis E virus (HEV), duck hepatitis B virus (DHBV), duck hepatitis A virus (DHAV-1, -2, -3), duck hepatitis virus Types 2 and 3, fowl adenoviruses (FAdV), and turkey hepatitis virus (THV). While these hepatitis viruses share the same target organ, the liver, they each possess unique clinical and biological features. In this article, we aim to review the common and unique features of major poultry hepatitis viruses in an effort to identify the knowledge gaps and aid the prevention and control of poultry viral hepatitis. Avian HEV is an Orthohepevirus B in the family Hepeviridae that naturally infects chickens and consists of three distinct genotypes worldwide. Avian HEV is associated with hepatitis-splenomegaly syndrome or big liver and spleen disease in chickens, although the majority of the infected birds are subclinical. Avihepadnaviruses in the family of Hepadnaviridae have been isolated from ducks, snow geese, white storks, grey herons, cranes, and parrots. DHBV evolved with the host as a noncytopathic form without clinical signs and rarely progressed to chronicity. The outcome for DHBV infection varies by the host's ability to elicit an immune response and is dose and age dependent in ducks, thus mimicking the pathogenesis of human hepatitis B virus (HBV) infections and providing an excellent animal model for human HBV. DHAV is a picornavirus that causes a highly contagious virus infection in ducks with up to 100% flock mortality in ducklings under 6 wk of age, while older birds remain unaffected. The high morbidity and mortality has an economic impact on intensive duck production farming. Duck hepatitis virus Types 2 and 3 are astroviruses in the family of Astroviridae with similarity phylogenetically to turkey astroviruses, implicating the potential for cross-species infections between strains. Duck astrovirus (DAstV) causes

  10. Neonatal Herpes Simplex Virus Infection.

    Science.gov (United States)

    James, Scott H; Kimberlin, David W

    2015-09-01

    Herpes simplex virus (HSV) 1 and HSV-2 infections are highly prevalent worldwide and are characterized by establishing lifelong infection with periods of latency interspersed with periodic episodes of reactivation. Acquisition of HSV by an infant during the peripartum or postpartum period results in neonatal HSV disease, a rare but significant infection that can be associated with severe morbidity and mortality, especially if there is dissemination or central nervous system involvement. Diagnostic and therapeutic advances have led to improvements in mortality and, to a lesser extent, neurodevelopmental outcomes, but room exists for further improvement. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Large-Scale Nucleotide Optimization of Simian Immunodeficiency Virus Reduces Its Capacity To Stimulate Type I Interferon In Vitro

    Science.gov (United States)

    Vabret, Nicolas; Bailly-Bechet, Marc; Lepelley, Alice; Najburg, Valérie; Schwartz, Olivier; Verrier, Bernard

    2014-01-01

    ABSTRACT Lentiviral RNA genomes present a strong bias in their nucleotide composition with extremely high frequencies of A nucleotide in human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV). Based on the observation that human optimization of RNA virus gene fragments may abolish their ability to stimulate the type I interferon (IFN-I) response, we identified the most biased sequences along the SIV genome and showed that they are the most potent IFN-I stimulators. With the aim of designing an attenuated SIV genome based on a reduced capacity to activate the IFN-I response, we synthesized artificial SIV genomes whose biased sequences were optimized toward macaque average nucleotide composition without altering their regulatory elements or amino acid sequences. A synthetic SIV optimized with 169 synonymous mutations in gag and pol genes showed a 100-fold decrease in replicative capacity. Interestingly, a synthetic SIV optimized with 70 synonymous mutations in pol had a normal replicative capacity. Its ability to stimulate IFN-I was reduced when infected cells were cocultured with reporter cells. IFN regulatory factor 3 (IRF3) transcription factor was required for IFN-I stimulation, implicating cytosolic sensors in the detection of SIV-biased RNA in infected cells. No reversion of introduced mutations was observed for either of the optimized viruses after 10 serial passages. In conclusion, we have designed large-scale nucleotide-modified SIVs that may display attenuated pathogenic potential. IMPORTANCE In this study, we synthesized artificial SIV genomes in which the most hyperbiased sequences were optimized to bring them closer to the nucleotide composition of the macaque SIV host. Interestingly, we generated a stable synthetic SIV optimized with 70 synonymous mutations in pol gene, which had a normal replicative capacity but a reduced ability to stimulate type I IFN. This demonstrates the possibility to rationally change viral

  12. Improvement of lymphocyte proliferation in human immunodeficiency virus infection after recombinant interleukin-2 treatment

    DEFF Research Database (Denmark)

    Afzelius, P; Nielsen, S D; Nielsen, Jens Ole

    1999-01-01

    In this study, the effect of recombinant interleukin-2 (rIL-2) on the function of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients was examined. Using polymerase chain reaction (PCR), an impaired ability of PBMC from 8 patients to respond upon...... mitogen stimulation with expression of IL-2 and IL-2 receptor (IL-2R) messenger ribonucleic acid (mRNA) was found compared with healthy donors (p = 0.02 and p = 0.05, respectively). Flow cytometry was used to determine the expression of p55 interleukin-2 alpha-receptor (CD25) after phytohaemagglutinin......, the induced gene expressions for IL-2 and IL-2R were positively correlated (p IL-2 and IL-2R genes in humans may share a common activation pathway, as has been found in monkeys infected by simian immunodeficiency virus (SIV). These results indicate...

  13. Transcriptional Profiling of Experimental CD8+ Lymphocyte Depletion in Rhesus Macaques Infected with Simian Immunodeficiency Virus SIVmac239

    Science.gov (United States)

    Bosinger, Steven E.; Jochems, Simon P.; Folkner, Kathryn A.; Hayes, Timothy L.; Klatt, Nichole R.

    2013-01-01

    CD8+ T cells inhibit virus replication in SIV-infected rhesus macaques. However, it is unclear to what extent the viral suppression mediated by CD8+ T cells reflects direct killing of infected cells as opposed to indirect, noncytolytic mechanisms. In this study, we used functional genomics to investigate noncytolytic mechanisms of in vivo viral suppression mediated by CD8+ lymphocytes. Eight chronically SIVmac239-infected rhesus macaques underwent CD8+ lymphocyte depletion, and RNA from whole blood was obtained prior to depletion, during the nadir of CD8+ cell depletion, and after CD8+ lymphocyte numbers had rebounded. We observed significant downregulation of the expression of genes encoding factors that can suppress SIV replication, including the CCR5-binding chemokine CCL5/RANTES and CCL4 and several members of the tripartite motif-containing (TRIM) family. Surprisingly, we also noted a strong, widespread downregulation of α- and θ-defensins with anti-HIV activity, which are not expressed by CD8+ T cells. After cessation of depleting antibody treatment, we observed induction of a transcriptional signature indicative of B lymphocyte activation. Validation experiments demonstrated that animals during this period had elevated levels of B cells coupled with higher expression of the proliferative marker Ki67, indicating that CD8+ depletion triggered a potent expansion of B cell numbers. Collectively, these data identify antiviral pathways perturbed by in vivo CD8+ T cell depletion that may contribute to noncytolytic control of SIV replication. PMID:23097439

  14. Probiotics in respiratory virus infections.

    Science.gov (United States)

    Lehtoranta, L; Pitkäranta, A; Korpela, R

    2014-08-01

    Viral respiratory infections are the most common diseases in humans. A large range of etiologic agents challenge the development of efficient therapies. Research suggests that probiotics are able to decrease the risk or duration of respiratory infection symptoms. However, the antiviral mechanisms of probiotics are unclear. The purpose of this paper is to review the current knowledge on the effects of probiotics on respiratory virus infections and to provide insights on the possible antiviral mechanisms of probiotics. A PubMed and Scopus database search was performed up to January 2014 using appropriate search terms on probiotic and respiratory virus infections in cell models, in animal models, and in humans, and reviewed for their relevance. Altogether, thirty-three clinical trials were reviewed. The studies varied highly in study design, outcome measures, probiotics, dose, and matrices used. Twenty-eight trials reported that probiotics had beneficial effects in the outcome of respiratory tract infections (RTIs) and five showed no clear benefit. Only eight studies reported investigating viral etiology from the respiratory tract, and one of these reported a significant decrease in viral load. Based on experimental studies, probiotics may exert antiviral effects directly in probiotic-virus interaction or via stimulation of the immune system. Although probiotics seem to be beneficial in respiratory illnesses, the role of probiotics on specific viruses has not been investigated sufficiently. Due to the lack of confirmatory studies and varied data available, more randomized, double-blind, and placebo-controlled trials in different age populations investigating probiotic dose response, comparing probiotic strains/genera, and elucidating the antiviral effect mechanisms are necessary.

  15. THE MOLECULAR EVOLUTION OF THE MOST DANGEROUS EMERGING VIRUS INFECTIONS

    Directory of Open Access Journals (Sweden)

    Popov NN

    2016-03-01

    barriers and infect new hosts. Really, many recently emerged human diseases are caused by viruses that display active recombination or reassortment. The continual shuffling of genes of influenza A represents a example of the key role of reassortment for the new virus emergence. Available data demonstrate the possible origin of SARS-CoV from recombination of different bat SL-CoVs viruses strains. However in other cases the emergence of a specific virus cannot be directly attributed to its ability to recombine. For example, although SIV recombines at a high rate in natural reservoirs, there is no evidence that recombination assisted the cross-species transfer of the virus from the chimpanzee into humans. But mutagenesis and recombination actively shape the further molecular history of HIV in humans. Also it is not proved that recombination precede the cross-species jump of the Ebola virus. In summary, the available data suggest that although recombination, reassortment and mutagenesis is sometimes directly involved to the process of cross-species transmission, it is not a necessary precursor to successful viral emergence. Further investigations are required to reveal the role of genetic change in the history of virus emergence. We believe that comprehensive description of molecular evolution of new viruses has led to a better understanding of the causes and predictability of infection emergence.

  16. Antiviral therapy in herpes- virus infections

    African Journals Online (AJOL)

    Repro

    pesviruses — herpes simplex virus (HSV), varicella zoster virus (VZV) ... virus infections. Herpesviruses are commonly seen in clinical practice. This article discusses their management in some detail. MAIN TOPIC. 332 C M E June 2003 Vol.21 No.6. After primary infection, ... A typical primary attack lasts about 10 - 14 days.

  17. Swine Influenza Viruses – Evolution and Zoonotic Potential

    DEFF Research Database (Denmark)

    Fobian, Kristina

    virulent viruses with the capacity to cause severe pandemics. Therefore, it is important to gain a deeper understanding of the evolution of SIVs, their zoonotic potential as well as host-range characteristics and this PhD project aimed at elucidating parts of these important points. The PhD thesis begins...... that potentially indicated drift away from current H1 viruses. The time of most recent common ancestor for H1 was estimated to be markedly earlier than previously suggested. Phylogenetic analysis of the Danish N2 gene revealed that two different lineages are circulating in Denmark. Manuscript II describes...... the biological characterization of four different Danish SIVs and includes an experimental pathogenesis study performed in ferrets, which are regarded as the most appropriate small animal model for human IAV infections. The viruses chosen for this study were two enzootic SIVs (H3N2 and H1N2) and two new SIV...

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

    Directory of Open Access Journals (Sweden)

    Barbara Tavano

    2017-03-01

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

  19. Distribution of sialic acid receptors and influenza A virus of avian and swine origin in experimentally infected pigs

    Directory of Open Access Journals (Sweden)

    Viuff Birgitte M

    2011-09-01

    Full Text Available Abstract Background Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SA-alpha-2,3 and swine/human (SA-alpha-2,6 influenza viruses in the upper respiratory tract. Furthermore, experimental and natural infections in pigs have been reported with influenza A virus from avian and human sources. Methods This study investigated the receptor distribution in the entire respiratory tract of pigs using specific lectins Maackia Amurensis (MAA I, and II, and Sambucus Nigra (SNA. Furthermore, the predilection sites of swine influenza virus (SIV subtypes H1N1 and H1N2 as well as avian influenza virus (AIV subtype H4N6 were investigated in the respiratory tract of experimentally infected pigs using immunohistochemical methods. Results SIV antigen was widely distributed in bronchi, but was also present in epithelial cells of the nose, trachea, bronchioles, and alveolar type I and II epithelial cells in severely affected animals. AIV was found in the lower respiratory tract, especially in alveolar type II epithelial cells and occasionally in bronchiolar epithelial cells. SA-alpha-2,6 was the predominant receptor in all areas of the respiratory tract with an average of 80-100% lining at the epithelial cells. On the contrary, the SA-alpha-2,3 was not present (0% at epithelial cells of nose, trachea, and most bronchi, but was found in small amounts in bronchioles, and in alveoli reaching an average of 20-40% at the epithelial cells. Interestingly, the receptor expression of both SA-alpha-2,3 and 2,6 was markedly diminished in influenza infected areas compared to non-infected areas. Conclusions A difference in predilection sites between SIV and AIV virus was found, and this difference was in accordance with the distribution of the SA-alpha-2,6 and SA-alpha-2,3 receptor, respectively. The results indicated

  20. Debilitating clinical disease in a wild-born captive western lowland gorilla (Gorilla gorilla gorilla) co-infected with varicella zoster virus (VZV) and simian T-lymphotropic virus (STLV).

    Science.gov (United States)

    Masters, Nicholas; Niphuis, Henk; Verschoor, Ernst; Breuer, Judith; Quinlivan, Mark; Wawrzynczyk, Teresa; Stidworthy, Mark

    2010-12-01

    A wild-born, 34-yr-old female western lowland gorilla (Gorilla gorilla gorilla) was transferred between zoologic collections in the United Kingdom. Adjustment to its new environment was difficult and a series of health problems ensued. Progressive severe illness of multiple etiologies, and a failure to respond to multiple therapies, led to its euthanasia 5 mo later. Disease processes included severe thoracic and axillary cutaneous ulceration of T2-3 dermatome distribution, gastroenteritis, ulcerative stomatitis, emaciation, hind limb weakness or paresis, and decubitus ulcers of the ankles and elbows. Ante- and postmortem infectious disease screening revealed that this animal was not infected with Mycobacterium tuberculosis, simian varicella virus (SVV), simian immunodeficiency virus (SIV), or hepatitis B virus; but was infected with varicella-zoster virus (VZV) and simian T-lymphotropic virus (STLV). It is hypothesized that recrudescence of VZV and other disease processes described were associated with chronic STLV infection and the end of a characteristically long incubation period.

  1. Cross-protection against European swine influenza viruses in the context of infection immunity against the 2009 pandemic H1N1 virus: studies in the pig model of influenza.

    Science.gov (United States)

    Qiu, Yu; De Hert, Karl; Van Reeth, Kristien

    2015-09-24

    Pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. In this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic H1N1 (pH1N1) virus and three different European H1 swine influenza virus (SIV) lineages, and b) these H1 viruses and a European H3N2 SIV. Pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-week intervals between H1 inoculations and between H1 and H3 inoculations, respectively. Virus titers in nasal swabs and/or tissues of the respiratory tract were determined after each inoculation. There was substantial though differing cross-protection between pH1N1 and other H1 viruses, which was directly correlated with the relatedness in the viral hemagglutinin (HA) and neuraminidase (NA) proteins. Cross-protection against H3N2 was almost complete in pigs with immunity against H1N2, but was weak in H1N1/pH1N1-immune pigs. In conclusion, infection with a live, wild type influenza virus may offer substantial cross-lineage protection against viruses of the same HA and/or NA subtype. True heterosubtypic protection, in contrast, appears to be minimal in natural influenza virus hosts. We discuss our findings in the light of the zoonotic and pandemic risks of SIVs.

  2. CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells.

    Directory of Open Access Journals (Sweden)

    Nichole R Klatt

    2010-01-01

    Full Text Available While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV and late (day 177 post-SIV chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication.

  3. [Zika virus infection in pregnancy].

    Science.gov (United States)

    Varjasi, Gabriella; Póka, Róbert

    2017-04-01

    The Zika virus is a flavivirus spread by mosquitoes. Its primary vectors are the Aedes aegypti and the Aedes albopictus. Before 2007 it sporadically caused benign morbidity. Since 2015, it started spreading "explosively" in America, especially in Brazil. In August 2016 they reported cases from New York and Poland, too. Most of the infections don't produce any symptoms, but can cause grave complications. The most important lesion is microcephalia that forms in fetuses. Microcephalia's most serious consequence is mental retardation, which puts great burden on both the family and the society. The viral infection increases the incidence of Guillain-Barré syndrome. This is an acute autoimmune disease which causes demyelination and, in the worst cases, it can also be fatal. Yet we do not possess adequate and specific vaccination nor antiviral therapy, although, since July 2016, the effectiveness of a DNA based vaccine is being tested on humans. More than half of the world's population lives in areas contaminated by infected mosquitoes so there is a great need for the development of an effective method against the vector mosquitoes. Sadly, even the vector control strategies aren't effective enough to push back the epidemic. Pregnant or fertile women must take the highest precautions against mosquito bites, especially if they travel to regions ravaged by the epidemic. The safest solution would be to postpone both the trip and the childbearing. In Europe, the vectors aren't spread enough to cause major threat, except maybe the warmer regions bordered by the Mediterranean Sea. However, it is possible that in the near future other viruses spread by Aedes mosquitoes could appear. Naturally, the travellers and immigrants, who came from endemic regions can also contribute to the spread of the epidemic. Thanks to the changes in global weather, there were reported findings of mosquitoes of the Aedes albopictus species in Hungary, which are slowly invading the continent, although

  4. Accumulation of Cytotoxic CD16+ NK Cells in Simian Immunodeficiency Virus-Infected Lymph Nodes Associated with In Situ Differentiation and Functional Anergy.

    Science.gov (United States)

    Schafer, Jamie L; Li, Haiying; Evans, Tristan I; Estes, Jacob D; Reeves, R Keith

    2015-07-01

    Recent evidence suggests that even in treated infections, human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication may continue in lymph nodes (LN), serving as a potential virus reservoir. Here we investigated the effects of lentivirus infection on natural killer (NK) cell frequencies, phenotypes, and functions in naive and acutely or chronically SIVmac239-infected rhesus macaques. Compared to that in naive animals, we observed a 3-fold-greater frequency of cytotoxic CD16(+) CD56(-) NK cells in LN of chronically infected macaques. However, NK cells did not appear to be trafficking to LN, as homing markers CD62L and CCR7 did not increase on circulating NK cells during infection. LN NK cells demonstrated enhanced cytotoxicity in acute infection, with 2-fold increases in perforin expression and 3-fold increases in CD107a expression following mitogen stimulation. Lysis of K562 cells by LN NK cells from acutely infected animals was greater than lysis by preinfection samples from the same animals. LN NK cells from chronically infected animals lysed K562 cells more efficiently than LN NK cells from uninfected animals, but importantly, surrogate markers of cytotoxicity in infected macaques were disproportionately greater than ex vivo killing. Furthermore, Tim-3, an indicator of activation and/or exhaustion, was upregulated 3-fold on LN NK cells in chronically infected animals. Collectively, these data suggest that LN NK cells are skewed toward a cytotoxic phenotype during SIV infection but may become dysfunctional and exhausted in chronic disease. The accumulation of CD16(+) CD56(-) NK cells in the SIV-infected lymph node without changes in NK homing to the LN could suggest that these cells are differentiating in situ. Surprisingly, this increase in frequency of the cytotoxic subset of NK cells is not accompanied by an increase of similar magnitude in the cytolytic function of LN lymphocytes. This functional modulation, together with the

  5. Combined single-cell quantitation of host and SIV genes and proteins ex vivo reveals host-pathogen interactions in individual cells.

    Science.gov (United States)

    Bolton, Diane L; McGinnis, Kathleen; Finak, Greg; Chattopadhyay, Pratip; Gottardo, Raphael; Roederer, Mario

    2017-06-01

    CD4 T cells harboring HIV-1/SIV represent a formidable hurdle to eradicating infection, and yet their detailed phenotype remains unknown. Here we integrate two single-cell technologies, flow cytometry and highly multiplexed quantitative RT-PCR, to characterize SIV-infected CD4 T cells directly ex vivo. Within individual cells, we correlate the cellular phenotype, in terms of host protein and RNA expression, with stages of the viral life cycle defined by combinatorial expression of viral RNAs. Spliced RNA+ infected cells display multiple memory and activation phenotypes, indicating virus production by diverse CD4 T cell subsets. In most (but not all) cells, progressive infection accompanies post-transcriptional downregulation of CD4 protein, while surface MHC class I is largely retained. Interferon-stimulated genes were also commonly upregulated. Thus, we demonstrate that combined quantitation of transcriptional and post-transcriptional regulation at the single-cell level informs in vivo mechanisms of viral replication and immune evasion.

  6. Quantitative plasma proteomic profiling identifies the vitamin E binding protein afamin as a potential pathogenic factor in SIV induced CNS disease.

    Science.gov (United States)

    Pendyala, Gurudutt; Trauger, Sunia A; Siuzdak, Gary; Fox, Howard S

    2010-01-01

    Investigating, predicting, diagnosing, and treating HIV-1-associated neurocognitive disorder (HAND) has been hindered by the lack of disease-related molecular markers. In this study, plasma from rhesus monkeys (n = 6), before and after infection with simian immunodeficiency virus (SIV), was profiled to obtain differential fingerprints in protein expression during SIV-induced central nervous system (CNS) disease. A quantitative proteomic analysis was performed by means of isobaric tag for relative and absolute quantification (iTRAQ) labeling, using multidimensional liquid chromatography tandem mass spectrometry (LC-MS/MS) run on a linear ion trap mass spectrometer in an integrated mode comprising pulsed-Q-dissociation (PQD) and CID. Among a panel of proteins showing differential expression following SIV infection, we identified afamin, a member of the albumin superfamily, to be significantly down regulated after infection. Validation by Western blot confirmed this observation and, given its potential implication in neuroprotection by transport of alpha-tocopherol (alphaTocH), provides new avenues into further understanding HIV induced CNS disease. iTRAQ-based LC-MS/MS provides a valuable platform for plasma protein profiling and has important implications in identifying molecular markers relevant for the pathogenesis of neurodegenerative diseases. Using such an approach, we show its successful application in identifying differential fingerprints in SIV/HIV induced CNS disease.

  7. TCR Affinity Associated with Functional Differences between Dominant and Subdominant SIV Epitope-Specific CD8+ T Cells in Mamu-A*01+ Rhesus Monkeys

    OpenAIRE

    Osuna, Christa E; Ana Maria Gonzalez; Hsun-Hsien Chang; Amy Shi Hung; Elizabeth Ehlinger; Kara Anasti; S Munir Alam; Letvin, Norman L.

    2014-01-01

    Many of the factors that contribute to CD8+ T cell immunodominance hierarchies during viral infection are known. However, the functional differences that exist between dominant and subdominant epitope-specific CD8+ T cells remain poorly understood. In this study, we characterized the phenotypic and functional differences between dominant and subdominant simian immunodeficiency virus (SIV) epitope-specific CD8+ T cells restricted by the major histocompatibility complex (MHC) class I allele Mam...

  8. Medicinal herbs for hepatitis C virus infection

    DEFF Research Database (Denmark)

    Liu, Jianping; Manheimer, Eric; Tsutani, Kiichiro

    2003-01-01

    The aim of this study was to assess beneficial and harmful effects of medicinal herbs for hepatitis C virus (HCV) infection.......The aim of this study was to assess beneficial and harmful effects of medicinal herbs for hepatitis C virus (HCV) infection....

  9. Persistent hepatitis virus infection and immune homeostasis

    OpenAIRE

    Zhou, Yun

    2014-01-01

    Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the pr...

  10. Structure and Immunogenicity of Alternative Forms of the Simian Immunodeficiency Virus Gag Protein Expressed Using Venezuelan Equine Encephalitis Virus Replicon Particles

    OpenAIRE

    Cecil, Chad; West, Ande; Collier, Martha; Jurgens, Christy; Madden, Victoria; Whitmore, Alan; Johnston, Robert; Moore, Dominic T.; Swanstrom, Ronald; Davis, Nancy L.

    2007-01-01

    Venezuelan equine encephalitis virus replicon particles (VRP) were engineered to express different forms of SIV Gag to compare expression in vitro, formation of intra- and extracellular structures and induction of humoral and cellular immunity in mice. The three forms examined were full-length myristylated SIV Gag (Gagmyr+), full-length Gag lacking the myristylation signal (Gagmyr-), or a truncated form of Gagmyr- comprising only the matrix and capsid domains (MA/CA). Comparison of VRP-infect...

  11. EPIDEMIOLOGY OF THE HERPES SIMPLEX VIRUS INFECTION

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    Ljiljana Kostadinović

    2002-07-01

    Full Text Available Over 150 sorts of viruses are capable of causing diseases of the respiratory ways. The virus infections have become the cost to be paid for urbanization and industrialization. The acute virus infections jeopardize mankind by their complications with numerous consequences. They open up the way to super infections, they provoke endogenous infections and lead to insufficiency of the vital organs. The viruses penetrate the organism mainly through the respiratory ways, digestive and urinary-sexual organs and skin. Some viruses immediately at the place of their entrance into the organism find receptive cells in which they can multiply (herpes virus and etc.. Some viruses must get through the blood, through the lymph or the nerve fibers to the target organs that they have affinity for.The changes that primarily occur in the mouth with manifest lymphadenopathy of the surrounding area emerge with respect to the type of the acute infection dis-ease.The human herpes viruses are responsible for a great number of diseases in people; that is why it can be said that the infections they induce are a very frequent cause of people's diseases in the world. Man is natural and the only host for the types I and II of the herpes simplex virus (HSV; that is why the infected person is regarded as the source of infection. The infection transmission can be by direct contact or over the contaminated secretions during the sexual intercourse. The age and the socioeconomic status (living conditions, level of medical culture, habits, etc. affect to agreat extent epidemiology of the HSV infection. The HSV distribution in the region of Niš in the five-year period (from 1987 to 1992 was the highest in the early and late summer (June and September.

  12. 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....

  13. Virus infection speeds: Theory versus experiment

    Science.gov (United States)

    Amor, Daniel R.; Fort, Joaquim

    2010-12-01

    In order to explain the speed of Vesicular Stomatitis Virus (VSV) infections, we develop a simple model that improves previous approaches to the propagation of virus infections. For VSV infections, we find that the delay time elapsed between the adsorption of a viral particle into a cell and the release of its progeny has a very important effect. Moreover, this delay time makes the adsorption rate essentially irrelevant in order to predict VSV infection speeds. Numerical simulations are in agreement with the analytical results. Our model satisfactorily explains the experimentally measured speeds of VSV infections.

  14. Full-Length Genome Analyses of Two New Simian Immunodeficiency Virus (SIV Strains from Mustached Monkeys (C. Cephus in Gabon Illustrate a Complex Evolutionary History among the SIVmus/mon/gsn Lineage

    Directory of Open Access Journals (Sweden)

    Florian Liégeois

    2014-07-01

    Full Text Available The Simian Immunodeficiency Virus (SIV mus/mon/gsn lineage is a descendant of one of the precursor viruses to the HIV-1/SIVcpz/gor viral lineage. SIVmus and SIVgsn were sequenced from mustached and greater spot nosed monkeys in Cameroon and SIVmon from mona monkeys in Cameroon and Nigeria. In order to further document the genetic diversity of SIVmus, we analyzed two full-length genomes of new strains identified in Gabon. The whole genomes obtained showed the expected reading frames for gag, pol, vif, vpr, tat, rev, env, nef, and also for a vpu gene. Analyses showed that the Gabonese SIVmus strains were closely related and formed a monophyletic clade within the SIVmus/mon/gsn lineage. Nonetheless, within this lineage, the position of both new SIVmus differed according to the gene analyzed. In pol and nef gene, phylogenetic topologies suggested different evolutions for each of the two new SIVmus strains whereas in the other nucleic fragments studied, their positions fluctuated between SIVmon, SIVmus-1, and SIVgsn. In addition, in C1 domain of env, we identified an insertion of seven amino acids characteristic for the SIVmus/mon/gsn and HIV‑1/SIVcpz/SIVgor lineages. Our results show a high genetic diversity of SIVmus in mustached monkeys and suggest cross-species transmission events and recombination within SIVmus/mon/gsn lineage. Additionally, in Central Africa, hunters continue to be exposed to these simian viruses, and this represents a potential threat to humans.

  15. Zika Virus: Mechanisms of Infection During Pregnancy.

    Science.gov (United States)

    King, Nicholas J C; Teixeira, Mauro M; Mahalingam, Suresh

    2017-09-01

    Immune status changes during pregnancy, with pro-inflammatory and anti-inflammatory contexts at different stages, making pregnant women potentially more susceptible to various infections. Infection by Zika virus during pregnancy can cause developmental damage to the fetus, and the altered immune response during pregnancy could contribute to disease during Zika infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Hendra Virus Infection in Dog, Australia, 2013.

    Science.gov (United States)

    Kirkland, Peter D; Gabor, Melinda; Poe, Ian; Neale, Kristie; Chaffey, Kim; Finlaison, Deborah S; Gu, Xingnian; Hick, Paul M; Read, Andrew J; Wright, Therese; Middleton, Deborah

    2015-12-01

    Hendra virus occasionally causes severe disease in horses and humans. In Australia in 2013, infection was detected in a dog that had been in contact with an infected horse. Abnormalities and viral RNA were found in the dog's kidney, brain, lymph nodes, spleen, and liver. Dogs should be kept away from infected horses.

  17. Influenza Virus Infection of Marine Mammals.

    Science.gov (United States)

    Fereidouni, Sasan; Munoz, Olga; Von Dobschuetz, Sophie; De Nardi, Marco

    2016-03-01

    Interspecies transmission may play a key role in the evolution and ecology of influenza A viruses. The importance of marine mammals as hosts or carriers of potential zoonotic pathogens such as highly pathogenic H5 and H7 influenza viruses is not well understood. The fact that influenza viruses are some of the few zoonotic pathogens known to have caused infection in marine mammals, evidence for direct transmission of influenza A virus H7N7 subtype from seals to man, transmission of pandemic H1N1 influenza viruses to seals and also limited evidence for long-term persistence of influenza B viruses in seal populations without significant genetic change, makes monitoring of influenza viruses in marine mammal populations worth being performed. In addition, such monitoring studies could be a great tool to better understand the ecology of influenza viruses in nature.

  18. Virus infections in patients with AIDS.

    Science.gov (United States)

    Griffiths, P D

    1990-01-01

    Virus infections are common in patients with acquired immune deficiency syndrome (AIDS). Viruses can have two distinct relationships with human immunodeficiency virus (HIV); they can be opportunists if the second virus takes advantage of decreased immune function in the host or they can act as co-factors to accelerate the rate at which AIDS develops. Viruses acting as opportunists may cause no symptoms or may be life-threatening. Several, including herpes simplex, varicella zoster, cytomegalovirus and Epstein-Barr virus, can be treated with antiviral agents. Before concluding that a virus can act as a co-factor for HIV, several other possible relationships must be excluded including opportunism, co-parameters of lifestyle and prognostic markers. Studies in vitro may suggest which viruses are potential co-factors but clear evidence can come only from carefully defined cohorts of patients. Recent evidence showing that cytomegalovirus can meet these criteria is presented.

  19. Zika Virus Infection: Current Concerns and Perspectives.

    Science.gov (United States)

    Maharajan, Mari Kannan; Ranjan, Aruna; Chu, Jian Feng; Foo, Wei Lim; Chai, Zhi Xin; Lau, Eileen YinYien; Ye, Heuy Mien; Theam, Xi Jin; Lok, Yen Ling

    2016-12-01

    The Zika virus outbreaks highlight the growing importance need for a reliable, specific and rapid diagnostic device to detect Zika virus, as it is often recognized as a mild disease without being identified. Many Zika virus infection cases have been misdiagnosed or underreported because of the non-specific clinical presentation. The aim of this review was to provide a critical and comprehensive overview of the published peer-reviewed evidence related to clinical presentations, various diagnostic methods and modes of transmission of Zika virus infection, as well as potential therapeutic targets to combat microcephaly. Zika virus is mainly transmitted through bites from Aedes aegypti mosquito. It can also be transmitted through blood, perinatally and sexually. Pregnant women are advised to postpone or avoid travelling to areas where active Zika virus transmission is reported, as this infection is directly linked to foetal microcephaly. Due to the high prevalence of Guillain-Barre syndrome and microcephaly in the endemic area, it is vital to confirm the diagnosis of Zika virus. Zika virus infection had been declared as a public health emergency and of international concern by the World Health Organisation. Governments and agencies should play an important role in terms of investing time and resources to fundamentally understand this infection so that a vaccine can be developed besides raising awareness.

  20. Immune responses to influenza virus infection.

    Science.gov (United States)

    Kreijtz, J H C M; Fouchier, R A M; Rimmelzwaan, G F

    2011-12-01

    Influenza viruses cause annual outbreaks of respiratory tract infection with attack rates of 5-10%. This means that humans are infected repeatedly with intervals of, on average, 10-20 years. Upon each infection subjects develop innate and adaptive immune responses which aim at clearing the infection. Strain-specific antibody responses are induced, which exert selective pressure on circulating influenza viruses and which drive antigenic drift of seasonal influenza viruses, especially in the hemagglutinin molecule. This antigenic drift necessitates updating of seasonal influenza vaccines regularly in order to match the circulating strains. Upon infection also virus-specific T cell responses are induced, including CD4+ T helper cells and CD8+ cytotoxic T cells. These cells are mainly directed to conserved proteins and therefore display cross-reactivity with a variety of influenza A viruses of different subtypes. T cell mediated immunity therefore may contribute to so-called heterosubtypic immunity and may afford protection against antigenically distinct, potentially pandemic influenza viruses. At present, novel viral targets are identified that may help to develop broad-protective vaccines. Here we review the various arms of the immune response to influenza virus infections and their viral targets and discuss the possibility of developing universal vaccines. The development of such novel vaccines would imply that also new immune correlates of protection need to be established in order to facilitate assessment of vaccine efficacy. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Interferon-γ Inhibits Ebola Virus Infection.

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    Bethany A Rhein

    Full Text Available Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  2. [Imported Zika virus infection in the Netherlands].

    Science.gov (United States)

    von Eije, Karin J; Schinkel, Janke; van den Kerkhof, J H C T Hans; Schreuder, Imke; de Jong, Menno D; Grobusch, Martin P; Goorhuis, Abraham

    2015-01-01

    Since mid-2015, a rapidly expanding outbreak of Zika virus infection is spreading across Latin America and the Caribbean. Although Zika virus infection usually causes only mild disease, the World Health Organization has declared the epidemiological association with the occurrence of congenital microcephaly and neurological complications a 'Public Health Emergency of International Concern' and urged the international community to mount a coordinated international response aimed to protect people at risk, especially pregnant women. In December 2015, the first case of imported Zika virus infection in the Netherlands was diagnosed in a returned traveler from Surinam. To date, more than 20 cases have been reported in The Netherlands, all imported from Surinam. We describe the epidemiology, clinical aspects, diagnostic challenges and the existing evidence to date that link Zika virus infection to complications.

  3. Minocycline Inhibition of Monocyte Activation Correlates with Neuronal Protection in SIV NeuroAIDS

    Science.gov (United States)

    Campbell, Jennifer H.; Burdo, Tricia H.; Autissier, Patrick; Bombardier, Jeffrey P.; Westmoreland, Susan V.; Soulas, Caroline; González, R. Gilberto; Ratai, Eva-Maria; Williams, Kenneth C.

    2011-01-01

    Background Minocycline is a tetracycline antibiotic that has been proposed as a potential conjunctive therapy for HIV-1 associated cognitive disorders. Precise mechanism(s) of minocycline's functions are not well defined. Methods Fourteen rhesus macaques were SIV infected and neuronal metabolites measured by proton magnetic resonance spectroscopy (1H MRS). Seven received minocycline (4 mg/kg) daily starting at day 28 post-infection (pi). Monocyte expansion and activation were assessed by flow cytometry, cell traffic to lymph nodes, CD16 regulation, viral replication, and cytokine production were studied. Results Minocycline treatment decreased plasma virus and pro-inflammatory CD14+CD16+ and CD14loCD16+ monocytes, and reduced their expression of CD11b, CD163, CD64, CCR2 and HLA-DR. There was reduced recruitment of monocyte/macrophages and productively infected cells in axillary lymph nodes. There was an inverse correlation between brain NAA/Cr (neuronal injury) and circulating CD14+CD16+ and CD14loCD16+ monocytes. Minocycline treatment in vitro reduced SIV replication CD16 expression on activated CD14+CD16+ monocytes, and IL-6 production by monocytes following LPS stimulation. Conclusion Neuroprotective effects of minocycline are due in part to reduction of activated monocytes, monocyte traffic. Mechanisms for these effects include CD16 regulation, reduced viral replication, and inhibited immune activation. PMID:21494695

  4. Dengue virus infection perturbs lipid homeostasis in infected mosquito cells.

    Directory of Open Access Journals (Sweden)

    Rushika Perera

    Full Text Available Dengue virus causes ∼50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  5. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    Energy Technology Data Exchange (ETDEWEB)

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  6. Functional RNA during Zika virus infection

    NARCIS (Netherlands)

    Göertz, Giel P.; Abbo, Sandra R.; Fros, Jelke J.; Pijlman, Gorben P.

    2017-01-01

    Zika virus (ZIKV; family Flaviviridae; genus Flavivirus) is a pathogenic mosquito-borne RNA virus that currently threatens human health in the Americas, large parts of Asia and occasionally elsewhere in the world. ZIKV infection is often asymptomatic but can cause severe symptoms including

  7. 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 ...

  8. 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.

  9. Virus Infections of Honeybees Apis Mellifera

    Science.gov (United States)

    Tantillo, Giuseppina; Bottaro, Marilisa; Di Pinto, Angela; Martella, Vito; Di Pinto, Pietro

    2015-01-01

    The health and vigour of honeybee colonies are threatened by numerous parasites (such as Varroa destructor and Nosema spp.) and pathogens, including viruses, bacteria, protozoa. Among honeybee pathogens, viruses are one of the major threats to the health and well-being of honeybees and cause serious concern for researchers and beekeepers. To tone down the threats posed by these invasive organisms, a better understanding of bee viral infections will be of crucial importance in developing effective and environmentally benign disease control strategies. Here we summarize recent progress in the understanding of the morphology, genome organization, transmission, epidemiology and pathogenesis of eight honeybee viruses: Deformed wing virus (DWV) and Kakugo virus (KV); Sacbrood virus (SBV); Black Queen cell virus (BQCV); Acute bee paralysis virus (ABPV); Kashmir bee virus (KBV); Israeli Acute Paralysis Virus (IAPV); Chronic bee paralysis virus (CBPV). The review has been designed to provide researchers in the field with updated information about honeybee viruses and to serve as a starting point for future research. PMID:27800411

  10. Virus infections of honeybees Apis Mellifera

    Directory of Open Access Journals (Sweden)

    Giuseppina Tantillo

    2015-09-01

    Full Text Available The health and vigour of honeybee colonies are threatened by numerous parasites (such as Varroa destructor and Nosema spp. and pathogens, including viruses, bacteria, protozoa. Among honeybee pathogens, viruses are one of the major threats to the health and wellbeing of honeybees and cause serious concern for researchers and beekeepers. To tone down the threats posed by these invasive organisms, a better understanding of bee viral infections will be of crucial importance in developing effective and environmentally benign disease control strategies. Here we summarize recent progress in the understanding of the morphology, genome organization, transmission, epidemiology and pathogenesis of eight honeybee viruses: Deformed wing virus (DWV and Kakugo virus (KV; Sacbrood virus (SBV; Black Queen cell virus (BQCV; Acute bee paralysis virus (ABPV; Kashmir bee virus (KBV; Israeli Acute Paralysis Virus (IAPV; Chronic bee paralysis virus (CBPV. The review has been designed to provide researchers in the field with updated information about honeybee viruses and to serve as a starting point for future research.

  11. Enhanced antibody responses elicited by a CpG adjuvant do not improve the protective effect of an aldrithiol-2-inactivated simian immunodeficiency virus therapeutic AIDS vaccine.

    Science.gov (United States)

    Wang, Yichuan; Blozis, Shelley A; Lederman, Michael; Krieg, Arthur; Landay, Alan; Miller, Christopher J

    2009-04-01

    The potential benefit of using unmethylated CpG oligoribodeoxynucleotides (ODN) as an adjuvant in a therapeutic simian immunodeficiency virus (SIV) vaccine consisting of AT2-inactivated SIVmac239 was evaluated in SIV-infected rhesus macaques receiving antiretroviral therapy (ART). We hypothesized that using CpG ODN as an adjuvant in therapeutic vaccination would enhance SIV-specific immune responses and suppress SIV replication after ART was stopped. To test our hypothesis, we immunized chronically SIV-infected rhesus macaques receiving ART with one of the following therapeutic vaccines: (i) AT2-inactivated SIVmac239, (ii) CpG10103 plus AT2-inactivated SIVmac239, (iii) CpG10103, and (iv) saline. While immunization with CpG plus AT2-SIVmac239 significantly increased SIV-specific immunoglobulin G (IgG) antibody titers, the mean plasma viral RNA (vRNA) level in these animals after ART did not differ from those of saline-treated animals. The AT2-inactivated SIVmac239-immunized animal group had a significantly higher mean SIV-specific gamma interferon T-cell response after three immunizations and lower plasma vRNA levels for 6 weeks after ART was withdrawn compared to the saline-treated animal group. Compared to the saline control group, the animal group treated with CpG alone had a significantly higher mean SIV-specific lymphocyte proliferation index and a higher rate of plasma vRNA rebound after ART. These results demonstrate that while the use of CpG as an adjuvant enhances SIV-specific antibody responses, this does not improve the control of SIV replication after ART is stopped. The lack of benefit may be related to the high levels of SIV-specific lymphocyte proliferation in the CpG adjuvant group.

  12. Limited role for the thymus in SIV pathogenesis

    NARCIS (Netherlands)

    Borghans, José A. M.; Hazenberg, Mette D.; Miedema, Frank

    2005-01-01

    The role of the thymus in the pathogenesis of AIDS is a frequently discussed and controversial topic. Tuttleton Arron et al. studied the role of thymic output in SIV infection directly, by comparing the dynamics of TCR excision circles and CD4(+ )and CD8(+) T cell numbers in healthy and in

  13. 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.

  14. Pathogenic infection of Macaca nemestrina with a CCR5-tropic subtype-C simian-human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Song Ruijiang

    2009-07-01

    Full Text Available Abstract Background Although pig-tailed macaques (Macaca nemestrina have been used in AIDS research for years, less is known about the early immunopathogenic events in this species, as compared to rhesus macaques (Macaca mulatta. Similarly, the events in early infection are well-characterized for simian immunodeficiency viruses (SIV, but less so for chimeric simian-human immunodeficiency viruses (SHIV, although the latter have been widely used in HIV vaccine studies. Here, we report the consequences of intrarectal infection with a CCR5-tropic clade C SHIV-1157ipd3N4 in pig-tailed macaques. Results Plasma and cell-associated virus was detectable in peripheral blood and intestinal tissues of all four pig-tailed macaques following intrarectal inoculation with SHIV-1157ipd3N4. We also observed a rapid and irreversible loss of CD4+ T cells at multiple mucosal sites, resulting in a marked decrease of CD4:CD8 T cell ratios 0.5–4 weeks after inoculation. This depletion targeted subsets of CD4+ T cells expressing the CCR5 coreceptor and having a CD28-CD95+ effector memory phenotype, consistent with the R5-tropism of SHIV-1157ipd3N4. All three animals that were studied beyond the acute phase seroconverted as early as week 4, with two developing cross-clade neutralizing antibody responses by week 24. These two animals also demonstrated persistent plasma viremia for >48 weeks. One of these animals developed AIDS, as shown by peripheral blood CD4+ T-cell depletion starting at 20 weeks post inoculation. Conclusion These findings indicate that SHIV-1157ipd3N4-induced pathogenesis in pig-tailed macaques followed a similar course as SIV-infected rhesus macaques. Thus, R5 SHIV-C-infection of pig-tailed macaques could provide a useful and relevant model for AIDS vaccine and pathogenesis research.

  15. DIESEL EXHAUST ENHANCES INFLUENZA VIRUS INFECTIONS IN RESPIRATORY EPITHELIAL CELLS

    Science.gov (United States)

    Several factors, such as age and nutritional status can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virus infections in rodent models. Influenza virus primarily infects ...

  16. Lectin switching during dengue virus infection.

    Science.gov (United States)

    Dejnirattisai, Wanwisa; Webb, Andrew I; Chan, Vera; Jumnainsong, Amonrat; Davidson, Andrew; Mongkolsapaya, Juthathip; Screaton, Gavin

    2011-06-15

    Dengue virus receptors are relatively poorly characterized, but there has been recent interest in 2 C-type lectin molecules, dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN) and its close homologue liver/lymph node-specific ICAM-3-grabbing integrin (L-SIGN), which can both bind dengue and promote infection. In this report we have studied the interaction of dengue viruses produced in insect cells, tumor cell lines, and primary human dendritic cells (DCs) with DC-SIGN and L-SIGN. Virus produced in primary DCs is unable to interact with DC-SIGN but remains infectious for L-SIGN-expressing cells. Skin-resident DCs may thus be a site of initial infection by insect-produced virus, but DCs will likely not participate in large-scale virus replication during dengue infection. These results reveal that differential glycosylation of dengue virus envelope protein is highly dependent on cell state and suggest that studies of virus tropism using virus prepared in insect cells or tumor cell lines should be interpreted with caution.

  17. Persistent hepatitis virus infection and immune homeostasis

    Directory of Open Access Journals (Sweden)

    ZHOU Yun

    2014-09-01

    Full Text Available Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the process involving various immune cells and molecules and is the result of homeostasis maintenance in antiviral immune response. The immune homeostasis maintained during persistent infections with hepatitis viruses is analyzed by the cellular and molecular mechanisms.

  18. 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...

  19. Atypical bacterial infections explained by a concomitant virus infection.

    Science.gov (United States)

    Dagan, R; Hall, C B; Menegus, M A

    1985-09-01

    Because both viral and bacterial infections are common during early childhood, dual infections are not unexpected. However, the clinical manifestation of such combined infections may be, difficult to interpret, and they are often misdiagnosed as "atypical bacterial infection." Five patients with concomitant viral-bacterial infections are described. In all five cases, virus detection enabled the physicians to better understand an otherwise puzzling clinical presentation. In view of the recent progress in rapid viral diagnoses and the potential of antiviral drugs, the possibility of dual infection should be investigated more often.

  20. Inhibition of enveloped viruses infectivity by curcumin.

    Directory of Open Access Journals (Sweden)

    Tzu-Yen Chen

    Full Text Available Curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. Previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (HA activity. This study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. In all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. In contrast, the nonenveloped enterovirus 71 remained unaffected by curcumin treatment. We evaluated the effects of curcumin on the membrane structure using fluorescent dye (sulforhodamine B; SRB-containing liposomes that mimic the viral envelope. Curcumin treatment induced the leakage of SRB from these liposomes and the addition of the influenza virus reduced the leakage, indicating that curcumin disrupts the integrity of the membranes of viral envelopes and of liposomes. When testing liposomes of various diameters, we detected higher levels of SRB leakage from the smaller-sized liposomes than from the larger liposomes. Interestingly, the curcumin concentration required to reduce plaque formation was lower for the influenza virus (approximately 100 nm in diameter than for the pseudorabies virus (approximately 180 nm and the vaccinia virus (roughly 335 × 200 × 200 nm. These data provide insights on the molecular antiviral mechanisms of curcumin and its potential use as an antiviral agent for enveloped viruses.

  1. 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 ...

  2. Antiviral therapy in herpes- virus infections

    African Journals Online (AJOL)

    Repro

    Herpesviruses are large, enveloped DNA viruses.There are currently 8 known human herpesviruses and 1 primate species that is a rare human pathogen. Most people have been infected with sev- eral human herpesviruses. In immuno- competent individuals primary infections with herpesviruses are generally mild, self-.

  3. Characterization of antigens expressed in normal baboon trophoblast and cross-reactive with HIV/SIV antibodies.

    Science.gov (United States)

    Langat, D K; Johnson, P M; Rote, N S; Wango, E O; Owiti, G O; Isahakia, M A; Mwenda, J M

    1999-01-01

    Electron microscopic studies have revealed the presence of endogenous retroviral (ERV) particles in normal primate placental tissues. These particles have ultrastructural similarities to type C retroviral particles and are mainly associated with the trophoblast. In normal human placental tissues, they have antigenic similarity with exogenous retroviruses, such as the human immunodeficiency virus (HIV), and may have a role to play in the regulation of cellular gene expression, syncytiotrophoblast formation or pregnancy-related immunosuppression. In this study, a panel of antibodies (polyclonal and monoclonal antibodies) against viral proteins (anti-HIV and anti-SIV) and endogenous retroviral (ERV) proteins were assessed by immunohistochemistry and immunoblotting, for their cross-reactivity with ERV particles isolated from normal baboon placental tissues. The antibodies (anti-HERV-K RT, anti-ERV3 env, anti-HIV-1 p17, anti-HIV-2 gp120) reacted positively with the syncytiotrophoblast and each antibody recognized one or two proteins of molecular weights (MW) 38, 58 or 64 kDa present in the baboon placental villous tissues and SIV-infected molt-4 Cl8 cells, but not in uninfected cells. The results of this study confirm the specific expression of retroviral cross-reactive antigens in normal baboon placental tissues and suggest placental cellular proteins may have antigenic similarity with those recognized by anti-HIV/SIV antibodies. The role of these retroviral-related proteins expressed at the maternal-fetal interface remain unclear.

  4. 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....

  5. Hepatitis C Virus Infection in Nigerians | Ejiofor | Nigerian Medical ...

    African Journals Online (AJOL)

    Background: Hepatitis C virus is a chronic life long infection in the majority of patients who are infected with the virus. Not much is known and written/published about this virus in Nigeria. Objective: To asses the status of hepatitis C virus infection in Nigeria. Materials and method: Sources of information were mainly from ...

  6. 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...

  7. Animal Models of Dengue Virus Infection

    OpenAIRE

    Eva Harris; Simona Zompi

    2012-01-01

    The development of animal models of dengue virus (DENV) infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs) can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe deng...

  8. Infection of phytoplankton by aerosolized marine viruses.

    Science.gov (United States)

    Sharoni, Shlomit; Trainic, Miri; Schatz, Daniella; Lehahn, Yoav; Flores, Michel J; Bidle, Kay D; Ben-Dor, Shifra; Rudich, Yinon; Koren, Ilan; Vardi, Assaf

    2015-05-26

    Marine viruses constitute a major ecological and evolutionary driving force in the marine ecosystems. However, their dispersal mechanisms remain underexplored. Here we follow the dynamics of Emiliania huxleyi viruses (EhV) that infect the ubiquitous, bloom-forming phytoplankton E. huxleyi and show that EhV are emitted to the atmosphere as primary marine aerosols. Using a laboratory-based setup, we showed that the dynamic of EhV aerial emission is strongly coupled to the host-virus dynamic in the culture media. In addition, we recovered EhV DNA from atmospheric samples collected over an E. huxleyi bloom in the North Atlantic, providing evidence for aerosolization of marine viruses in their natural environment. Decay rate analysis in the laboratory revealed that aerosolized viruses can remain infective under meteorological conditions prevailing during E. huxleyi blooms in the ocean, allowing potential dispersal and infectivity over hundreds of kilometers. Based on the combined laboratory and in situ findings, we propose that atmospheric transport of EhV is an effective transmission mechanism for spreading viral infection over large areas in the ocean. This transmission mechanism may also have an important ecological impact on the large-scale host-virus "arms race" during bloom succession and consequently the turnover of carbon in the ocean.

  9. Overcoming maternal antibody interference by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of swine influenza virus.

    Science.gov (United States)

    Wesley, Ronald D; Lager, Kelly M

    2006-11-26

    Sows and gilts lack immunity to human adenovirus 5 (Ad-5) vectored vaccines so immunogens of swine pathogens can be expressed with these vaccines in order to immunize suckling piglets that have interfering, maternally derived antibodies. In this study 7-day-old piglets, that had suckled H3N2 infected gilts, were sham-inoculated with a non-expressing Ad-5 vector or given a primary vaccination with replication-defective Ad-5 viruses expressed the H3 hemagglutinin and the nucleoprotein of swine influenza virus (SIV) subtype H3N2. The hemagglutination inhibition (HI) titer of the sham-inoculated group (n = 12) showed continued antibody decay whereas piglets vaccinated with Ad-5 SIV (n = 23) developed an active immune response by the second week post-vaccination. At 4 weeks-of-age when the HI titer of the sham-inoculated group had decayed to 45, the sham-inoculated group and half of the Ad-5 SIV vaccinated pigs were boosted with a commercial inactivated SIV vaccine. The boosted pigs that had been primed in the presence of maternal interfering antibodies had a strong anamnestic response while sham-inoculated pigs did not respond to the commercial vaccine. Two weeks after the booster vaccination the pigs were challenged with a non-homologous H3N2 virulent SIV. The efficacy of the vaccination protocol was demonstrated by abrogation of clinical signs, by clearance of challenge virus from pulmonary lavage fluids, by markedly reduced virus shedding in nasal secretions, and by the absence of moderate or severe SIV-induced lung lesions. These recombinant Ad-5 SIV vaccines are useful for priming the immune system to override the effects of maternally derived antibodies which interfere with conventional SIV vaccines.

  10. Type I Interferon Upregulates Bak and Contributes to T Cell Loss during Human Immunodeficiency Virus (HIV) Infection

    Science.gov (United States)

    Fraietta, Joseph A.; Mueller, Yvonne M.; Yang, Guibin; Boesteanu, Alina C.; Gracias, Donald T.; Do, Duc H.; Hope, Jennifer L.; Kathuria, Noshin; McGettigan, Shannon E.; Lewis, Mark G.; Giavedoni, Luis D.; Jacobson, Jeffrey M.; Katsikis, Peter D.

    2013-01-01

    The role of Type I interferon (IFN) during pathogenic HIV and SIV infections remains unclear, with conflicting observations suggesting protective versus immunopathological effects. We therefore examined the effect of IFNα/β on T cell death and viremia in HIV infection. Ex vivo analysis of eight pro- and anti-apoptotic molecules in chronic HIV-1 infection revealed that pro-apoptotic Bak was increased in CD4+ T cells and correlated directly with sensitivity to CD95/Fas-mediated apoptosis and inversely with CD4+ T cell counts. Apoptosis sensitivity and Bak expression were primarily increased in effector memory T cells. Knockdown of Bak by RNA interference inhibited CD95/Fas-induced death of T cells from HIV-1-infected individuals. In HIV-1-infected patients, IFNα-stimulated gene expression correlated positively with ex vivo T cell Bak levels, CD95/Fas-mediated apoptosis and viremia and negatively with CD4+ T cell counts. In vitro IFNα/β stimulation enhanced Bak expression, CD95/Fas expression and CD95/Fas-mediated apoptosis in healthy donor T cells and induced death of HIV-specific CD8+ T cells from HIV-1-infected patients. HIV-1 in vitro sensitized T cells to CD95/Fas-induced apoptosis and this was Toll-like receptor (TLR)7/9- and Type I IFN-dependent. This sensitization by HIV-1 was due to an indirect effect on T cells, as it occurred in peripheral blood mononuclear cell cultures but not purified CD4+ T cells. Finally, peak IFNα levels and viral loads correlated negatively during acute SIV infection suggesting a potential antiviral effect, but positively during chronic SIV infection indicating that either the virus drives IFNα production or IFNα may facilitate loss of viral control. The above findings indicate stage-specific opposing effects of Type I IFNs during HIV-1 infection and suggest a novel mechanism by which these cytokines contribute to T cell depletion, dysregulation of cellular immunity and disease progression. PMID:24130482

  11. Uterine adenocarcinoma with feline leukemia virus infection

    OpenAIRE

    Cho, Sung-Jin; Lee, Hyun-A; Hong, SunHwa; Kim, Okjin

    2011-01-01

    Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase c...

  12. Parainfluenza virus 5 expressing the G protein of rabies virus protects mice after rabies virus infection.

    Science.gov (United States)

    Huang, Ying; Chen, Zhenhai; Huang, Junhua; Fu, ZhenFang; He, Biao

    2015-03-01

    Rabies remains a major public health threat around the world. Once symptoms appear, there is no effective treatment to prevent death. In this work, we tested a recombinant parainfluenza virus 5 (PIV5) strain expressing the glycoprotein (G) of rabies (PIV5-G) as a therapy for rabies virus infection: we have found that PIV5-G protected mice as late as 6 days after rabies virus infection. PIV5-G is a promising vaccine for prevention and treatment of rabies virus infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Protection of guinea pigs by vaccination with a recombinant swinepox virus co-expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.

    Science.gov (United States)

    Xu, Jiarong; Yang, Deji; Huang, Dongyan; Xu, Jiaping; Liu, Shichao; Lin, Huixing; Zhu, Haodan; Liu, Bao; Lu, Chengping

    2013-03-01

    Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P guinea pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

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

    NARCIS (Netherlands)

    A.C. van der Kuyl (Antoinette); R. van den Burg (Remco); M.J. Hoyer (Mark); R.A. Gruters (Rob); A.D.M.E. Osterhaus (Albert); B. Berkhout (Ben)

    2004-01-01

    textabstractA pol-fragment of simian immunodeficiency virus (SIV) that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus) was detected in two mandrills (Mandrillus sphinx) from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and

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

    NARCIS (Netherlands)

    van der Kuyl, Antoinette C.; van den Burg, Remco; Hoyer, Mark J.; Gruters, Rob A.; Osterhaus, Albert D. M. E.; Berkhout, Ben

    2004-01-01

    A pol-fragment of simian immunodeficiency virus (SIV) that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus) was detected in two mandrills (Mandrillus sphinx) from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely

  16. Drug Targets in Infections With Ebola and Marburg Viruses

    Science.gov (United States)

    2009-01-01

    Venezuelan equine encephalitis (VEE) virus -like replicon (VRP), adenovirus 5 (AdS), vesicular stomatitis virus ( VSV )-based vaccines, and virus -like... virus itself may prove to be a very effective way to clear or prevent virus infection, an inherent flaw in this method does exist for several viruses ...immunofluorescence and ELISA. Rab9 siRNA also decreased replication of HIV and measles virus . This was not observed in non~enveloped viruses , which

  17. Respiratory syncytial virus infection in children.

    Science.gov (United States)

    Dawson-Caswell, Marin; Muncie, Herbert L

    2011-01-15

    Respiratory syncytial virus (RSV) is an RNA virus that causes respiratory tract infections in children. In the North- ern Hemisphere, the peak infection season is November through April. By two years of age, most children will have had an RSV infection. Bronchiolitis, a lower respiratory tract infection, is often caused by RSV. An RSV infection is diagnosed based on patient history and physical examination. Children typically present with cough, coryza, and wheezing. Laboratory testing and chest radiography are not necessary to make the diagnosis. Serious concur- rent bacterial infections are rare. Treatment of an RSV infection is supportive, with particular attention to maintaining hydration and oxygenation. Children younger than 60 days and those with severe symptoms may require hospitalization. Neither antibiotics nor corticosteroids are helpful for bronchiolitis. A bronchodilator trial is appropriate for children with wheezing, but should not be continued unless there is a prompt favorable response. Frequent hand washing and contact isolation may prevent the spread of RSV infections. Children younger than two years at high risk of severe illness, including those born before 35 weeks of gestation and those with chronic lung or cardiac problems, may be candidates for palivizumab prophylaxis for RSV infection during the peak infection season. Most children recover uneventfully with supportive care.

  18. Borna disease virus infection in cats.

    Science.gov (United States)

    Wensman, Jonas Johansson; Jäderlund, Karin Hultin; Holst, Bodil Ström; Berg, Mikael

    2014-08-01

    Bornaviruses are known to cause neurological disorders in a number of animal species. Avian Bornavirus (ABV) causes proventricular dilatation disease (PDD) in birds and Borna disease virus (BDV) causes Borna disease in horses and sheep. BDV also causes staggering disease in cats, characterised by ataxia, behavioural changes and loss of postural reactions. BDV-infection markers in cats have been reported throughout the world. This review summarizes the current knowledge of Borna disease viruses in cats, including etiological agent, clinical signs, pathogenesis, epidemiology and diagnostics, with comparisons to Bornavirus infections in other species. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Immune Responses and Lassa Virus Infection

    Science.gov (United States)

    Russier, Marion; Pannetier, Delphine; Baize, Sylvain

    2012-01-01

    Lassa fever is a hemorrhagic fever endemic to West Africa and caused by Lassa virus, an Old World arenavirus. It may be fatal, but most patients recover from acute disease and some experience asymptomatic infection. The immune mechanisms associated with these different outcomes have not yet been fully elucidated, but considerable progress has recently been made, through the use of in vitro human models and nonhuman primates, the only relevant animal model that mimics the pathophysiology and immune responses induced in patients. We discuss here the roles of the various components of the innate and adaptive immune systems in Lassa virus infection and in the control of viral replication and pathogenesis. PMID:23202504

  20. 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 ...

  1. Plant virus infections control stomatal development

    Science.gov (United States)

    Murray, Rose R.; Emblow, Mark S. M.; Hetherington, Alistair M.; Foster, Gary D.

    2016-09-01

    Stomata are important regulators of carbon dioxide uptake and transpirational water loss. They also represent points of vulnerability as bacterial and fungal pathogens utilise this natural opening as an entry portal, and thus have an increasingly complex relationship. Unlike the situation with bacterial and fungal pathogens, we know very little about the role of stomata in viral infection. Here we report findings showing that viral infection influences stomatal development in two susceptible host systems (Nicotiana tabacum with TMV (Tobacco mosaic virus), and Arabidopsis thaliana with TVCV (Turnip vein-clearing virus)), but not in resistant host systems (Nicotiana glutinosa and Chenopodium quinoa with TMV). Virus infected plants had significantly lower stomatal indices in systemic leaves of susceptible systems; N. tabacum 9.8% reduction and A. thaliana 12.3% reduction, but not in the resistant hosts. Stomatal density in systemic leaves was also significantly reduced in virus infected A. thaliana by 19.6% but not in N. tabacum or the resistant systems. In addition, transpiration rate was significantly reduced in TMV infected N. tabacum.

  2. Marine Viruses that infect Eukaryotic Microalgae.

    Science.gov (United States)

    Kimura, Kei; Tomaru, Yuji

    2015-01-01

    Marine microalgae, in general, explain large amount of the primary productions on the planet. Their huge biomass through photosynthetic activities is significant to understand the global geochemical cycles. Many researchers are, therefore, focused on studies of marine microalgae, i.e. phytoplankton. Since the first report of high abundance of viruses in the sea at late 1980's, the marine viruses have recognized as an important decreasing factor of its host populations. They seem to be composed of diverse viruses infectious to different organism groups; most of them are considered to be phages infectious to prokaryotes, and viruses infecting microalgae might be ranked in second level. Over the last quarter of a century, the knowledge on marine microalgal viruses has been accumulated in many aspects. Until today, ca. 40 species of marine microalgal viruses have been discovered, including dsDNA, ssDNA, dsRNA and ssRNA viruses. Their features are unique and comprise new ideas and discoveries, indicating that the marine microalgal virus research is still an intriguing unexplored field. In this review, we summarize their basic biology and ecology, and discuss how and what we should research in this area for further progress.

  3. Symptoms of influenza virus infection in hospitalized patients

    NARCIS (Netherlands)

    van den Dool, C; Hak, E; Wallinga, J; van Loon, A M; Lammers, J W J; Bonten, M J M

    BACKGROUND: During influenza outbreaks, fever and cough are the most accurate symptoms in predicting influenza virus infection in the community. OBJECTIVE: To determine the usefulness of fever, cough, and other symptoms for diagnosing influenza virus infection in hospitalized patients. DESIGN:

  4. USEFULNESS OF THE GRAPEVINE VIRUS-INFECTED COLLECTION

    Directory of Open Access Journals (Sweden)

    Elena-Cocuţa Buciumeanu

    2012-04-01

    Full Text Available In order to use the virus-infected material as reference in various studies, a grapevine virus collection was established at NRDIBH Ştefănşti-Argeş. The vines are infected with 1-3 of the main specific viruses of this crop: fanleaf virus, leafroll associated virus serotypes 1+3, fleck virus and virus A. Different lots of plants belonging to the same cultivar are infected with different viruses. The own rooted or grafted potted plants are maintained in an insect-proof greenhouse. The main goals of the study of grapevine under the influence of virus infection had in view: symptoms, in vitro behaviour of virus infected grapevine, virus elimination, plant positive control in the diagnostic process. The symptoms produced by viral infection can affect the whole plant (systemic symptoms or they are visible on certain parts of the plant (local symptoms. In vitro studies of virus infected grapevines comparatively with the healthy material aimed with the quantitative and qualitative aspects of the culture: multiplication and rooting rates, shoots elongation, abnormal cuttings and vitrification phenomena. Infected grapevine cultivars and clones were subjected to virus elimination through thermotherapy, chemotherapy or electrotherapy, combined with in vitro culture. The diagnosis of leafroll, fleck, vein necrosis and corky bark diseases have been done by in vitro micrografting, as rapid biological method of virus detection. Samples collected from infected vines were used as material testing for virus detection by ELISA in inter-laboratory comparisons and Iaboratory-performed validation.

  5. Zika virus infection of Hofbauer cells.

    Science.gov (United States)

    Simoni, Michael K; Jurado, Kellie Ann; Abrahams, Vikki M; Fikrig, Erol; Guller, Seth

    2017-02-01

    Recent studies have linked antenatal infection with Zika virus (ZIKV) with major adverse fetal and neonatal outcomes, including microcephaly. There is a growing consensus for the existence of a congenital Zika syndrome (CZS). Previous studies have indicated that non-placental macrophages play a key role in the replication of dengue virus (DENV), a closely related flavivirus. As the placenta provides the conduit for vertical transmission of certain viruses, and placental Hofbauer cells (HBCs) are fetal-placental macrophages located adjacent to fetal capillaries, it is not surprising that several recent studies have examined infection of HBCs by ZIKV. In this review, we describe congenital abnormalities associated with ZIKV infection, the role of HBCs in the placental response to infection, and evidence for the susceptibility of HBCs to ZIKV infection. We conclude that HBCs may contribute to the spread of ZIKV in placenta and promote vertical transmission of ZIKV, ultimately compromising fetal and neonatal development and function. Current evidence strongly suggests that further studies are warranted to dissect the specific molecular mechanism through which ZIKV infects HBCs and its potential impact on the development of CZS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1.

    Science.gov (United States)

    Keele, Brandon F; Li, Hui; Learn, Gerald H; Hraber, Peter; Giorgi, Elena E; Grayson, Truman; Sun, Chuanxi; Chen, Yalu; Yeh, Wendy W; Letvin, Norman L; Mascola, John R; Nabel, Gary J; Haynes, Barton F; Bhattacharya, Tanmoy; Perelson, Alan S; Korber, Bette T; Hahn, Beatrice H; Shaw, George M

    2009-05-11

    We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA 1-5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1-5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV-macaque mucosal infection model for HIV-1 vaccine and microbicide research.

  7. Uterine adenocarcinoma with feline leukemia virus infection.

    Science.gov (United States)

    Cho, Sung-Jin; Lee, Hyun-A; Hong, Sunhwa; Kim, Okjin

    2011-12-01

    Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection.

  8. Hepatitis C Virus Infection In Nigerianswith Diabetesmellitus ...

    African Journals Online (AJOL)

    Background/Aims: Studies from mainly Caucasian populations have shown epidemiological evidence of an association between diabetes mellitus and Hepatitis C virus (HCV) infection. The aim of this study was to determine whether any such association exists in a black African population with diabetes mellitus. Method: ...

  9. 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...

  10. Chronic arthritis in chikungunya virus infection.

    Science.gov (United States)

    Mateo, Lourdes; Roure, Silvia

    2017-07-24

    Chikungunya virus infection causes arthralgia and arthritis in the acute phase of the disease but, in more than half of the cases, musculoskeletal manifestations can be prolonged over time and, in some cases, become chronic. Although polyarthralgia is the most frequent chronic manifestation, forms with polyarthritis, tenosynovitis and enthesopathy are also common. To analyze the clinical characteristics of patients with persistent articular manifestations after infection with the Chikungunya virus. Report of 3 cases of chronic arthritis after infection with chikungunya virus diagnosed at outpatient care in a university hospital of Catalonia, all of them imported after exposure in areas of epidemic infection between 2013-2015. All three patients had inflammatory joint pain for more than one year after acute disease (3, 2 and 1 years, respectively). In all cases, it appeared as polyarthritis with involvement of small joints of hands and feet (pseudorheumatoid arthritis-like). Laboratory tests showed a slight elevation of acute phase reactants, and analyses for immune markers were negative. Two of the patients required treatment with glucocorticoids and hydroxychloroquine. The course led to slow clinical improvement, but only one of them came to be completely asymptomatic. In the differential diagnosis of chronic polyarthritis, Chikungunya virus disease should also be considered in areas in which it is not endemic. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  11. 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 ...

  12. Mechanisms underlying Cowpea mosaic virus systemic infection

    NARCIS (Netherlands)

    Santos Silva, M.

    2004-01-01

    Systemic virus infection of plants involves; intracellularreplication, cell-to-cell movement within the inoculated leaf, and subsequently, long-distance spread to other plant parts via the vasculature (vascular movement).Cell-to-cell movement

  13. Epidemiology of Hepatitis B and Hepatitis C Virus infections among ...

    African Journals Online (AJOL)

    Hepatitis B and hepatitis C virus infection are common in Nigeria; where they are a major cause of both acute and chronic liver disease, as well as hepatocellular cancer. Persons at risk of acquisition of Human Immunodeficiency Virus (HIV) infection are also at risk of acquisition of infection with Hepatitis B virus (HBV) and ...

  14. Immunodomination during peripheral vaccinia virus infection.

    Directory of Open Access Journals (Sweden)

    Leon C W Lin

    Full Text Available Immunodominance is a fundamental property of CD8(+ T cell responses to viruses and vaccines. It had been observed that route of administration alters immunodominance after vaccinia virus (VACV infection, but only a few epitopes were examined and no mechanism was provided. We re-visited this issue, examining a panel of 15 VACV epitopes and four routes, namely intradermal (i.d., subcutaneous (s.c., intraperitoneal (i.p. and intravenous (i.v. injection. We found that immunodominance is sharpened following peripheral routes of infection (i.d. and s.c. compared with those that allow systemic virus dissemination (i.p. and i.v.. This increased immunodominance was demonstrated with native epitopes of VACV and with herpes simplex virus glycoprotein B when expressed from VACV. Responses to some subdominant epitopes were altered by as much as fourfold. Tracking of virus, examination of priming sites, and experiments restricting virus spread showed that priming of CD8(+ T cells in the spleen was necessary, but not sufficient to broaden responses. Further, we directly demonstrated that immunodomination occurs more readily when priming is mainly in lymph nodes. Finally, we were able to reduce immunodominance after i.d., but not i.p. infection, using a VACV expressing the costimulators CD80 (B7-1 and CD86 (B7-2, which is notable because VACV-based vaccines incorporating these molecules are in clinical trials. Taken together, our data indicate that resources for CD8(+ T cell priming are limiting in local draining lymph nodes, leading to greater immunodomination. Further, we provide evidence that costimulation can be a limiting factor that contributes to immunodomination. These results shed light on a possible mechanism of immunodomination and highlight the need to consider multiple epitopes across the spectrum of immunogenicities in studies aimed at understanding CD8(+ T cell immunity to viruses.

  15. West Nile Virus Infection in Sheep.

    Science.gov (United States)

    Rimoldi, G; Mete, A; Adaska, J M; Anderson, M L; Symmes, K P; Diab, S

    2017-01-01

    West Nile virus (WNV) infection has been detected in many species of birds and mammals, but scant information is available about the disease in small ruminants. West Nile virus was diagnosed in 6 sheep with neurological signs and encephalitis, in California between 2002 and 2014. All sheep had severe lymphoplasmacytic meningoencephalitis. Lymphoplasmacytic myelitis was also detected in 2 sheep where the spinal cord was examined. Brain tissue was positive for WNV detected by polymerase chain reaction in 6 of 6 sheep and by immunohistochemistry (IHC) in 5 of 6 sheep. Viral antigen was not detected by IHC in extraneural tissues in the 3 sheep examined. West Nile virus RNA was sequenced from 2 of 6 sheep, and each one clusters closely with WNV isolated from mosquito pools from nearby locations at similar times. West Nile virus was the most common cause of viral encephalitis in sheep diagnosed at this laboratory between 2002 and 2014, accounting for 6 of 9 sheep.

  16. Immunobiology of Ebola and Lassa virus infections.

    Science.gov (United States)

    Prescott, Joseph B; Marzi, Andrea; Safronetz, David; Robertson, Shelly J; Feldmann, Heinz; Best, Sonja M

    2017-03-01

    Two of the most important contemporary emerging viruses that affect human health in Africa are Ebola virus (EBOV) and Lassa virus (LASV). The 2013-2016 West African outbreak of EBOV was responsible for more than 11,000 deaths, primarily in Guinea, Sierra Leone and Liberia. LASV is constantly emerging in these and surrounding West African countries, with an estimate of more than 500,000 cases of Lassa fever, and approximately 5,000 deaths, annually. Both EBOV and LASV are zoonotic, and human infection often results in a severe haemorrhagic fever in both cases. However, the contribution of specific immune responses to disease differs between EBOV and LASV. This Review examines innate and adaptive immune responses to these viruses with the goal of delineating responses that are associated with protective versus pathogenic outcomes.

  17. Full molecular characterization of a simian immunodeficiency virus, SIVwrcpbt from Temminck's red colobus (Piliocolobus badius temminckii) from Abuko Nature Reserve, The Gambia.

    Science.gov (United States)

    Locatelli, Sabrina; Lafay, Bénédicte; Liegeois, Florian; Ting, Nelson; Delaporte, Eric; Peeters, Martine

    2008-06-20

    Simian immunodeficiency viruses (SIVs) are found in an extensive number of African primates, and humans continue to be exposed to these viruses by hunting and handling of primate bushmeat. The purpose of our study was to examine to what extent Piliocolobus badius subspecies are infected with SIV in order to better characterize SIVwrc in general and to gain further insight into the impact of geographic barriers and subspeciation on the evolution of SIVwrc. We analysed sixteen faecal samples and two tissue samples of the P. b. temminckii subspecies collected in the Abuko Nature Reserve (The Gambia, West Africa). SIV infection could only be identified in one tissue sample, and phylogenetic tree analyses of partial pol and env sequences showed that the new SIVwrcPbt virus is closely related to SIVwrcPbb strains from P. b. badius in the Taï forest (Côte d'Ivoire), thus suggesting that geographically separated subspecies are infected with a closely related virus. Molecular characterization and phylogenetic analysis of the full-length genome sequence confirmed that SIVwrcPbt is a species-specific SIV lineage, although it is distantly related to the SIVlho and SIVsun lineages across its entire genome. Characterization of additional SIVwrc viruses is needed to understand the ancestral phylogenetic relation to SIVs from l'Hoest and sun-tailed monkeys and whether recombination occurred between ancestors of the SIVwrc and SIVlho/sun lineages.

  18. 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.

  19. Hematologic manifestations of feline immunodeficiency virus infection.

    Science.gov (United States)

    Shelton, G H; Linenberger, M L; Grant, C K; Abkowitz, J L

    1990-09-15

    Studies were done on 53 cats with community-acquired infection with the feline immunodeficiency virus (FIV) to determine if hematologic abnormalities were comparable with those observed in patients seropositive for the human immunodeficiency virus (HIV). Nine cats were asymptomatic, 24 had clinical symptoms equivalent to AIDS-related complex (ARC), and 20 had AIDS-like disease. Hematologic abnormalities were detected in 75% (40 of 53) of FIV-seropositive cats, and multiple concurrent cytopenias were common. Anemia, lymphopenia, neutropenia, and thrombocytopenia occurred in 36%, 53%, 34%, and 8% of FIV-seropositive cats, respectively. Cytopenias were seen only in symptomatic (ARC or AIDS) cats. The occurrence of cytopenias and the distribution of clinical stages were similar in cats with concurrent feline leukemia virus (FeLV) infection and those with FIV alone, suggesting that these abnormalities were a direct consequence of FIV infection. In addition, abnormalities were noted in 72% of marrows from symptomatic cats and included hyperplasia of individual cell lineages and dysmorphic features. Our results demonstrate that the hematologic manifestations of FIV infection are strikingly similar to those reported in HIV-seropositive patients. Thus, FIV infection in cats is an excellent animal model to study the pathogenesis of blood and marrow abnormalities in AIDS, as well as to evaluate the hematologic toxicities of drug therapies.

  20. Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections.

    Directory of Open Access Journals (Sweden)

    Jacob D Estes

    Full Text Available The chronic phase of HIV infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or CD4(+ T cell count. Recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed tissues from SIV-infected rhesus macaques (RMs to provide direct in situ evidence for translocation of microbial constituents from the lumen of the intestine into the lamina propria and to draining and peripheral lymph nodes and liver, accompanied by local immune responses in affected tissues. In chronically SIV-infected RMs this translocation is associated with breakdown of the integrity of the epithelial barrier of the gastrointestinal (GI tract and apparent inability of lamina propria macrophages to effectively phagocytose translocated microbial constituents. By contrast, in the chronic phase of SIV infection in sooty mangabeys, we found no evidence of epithelial barrier breakdown, no increased microbial translocation and no pathological immune activation. Because immune activation is characteristic of the chronic phase of progressive HIV/SIV infections, these findings suggest that increased microbial translocation from the GI tract, in excess of capacity to clear the translocated microbial constituents, helps drive pathological immune activation. Novel therapeutic approaches to inhibit microbial translocation and/or attenuate chronic immune activation in HIV-infected individuals may complement treatments aimed at direct suppression of viral replication.

  1. Dengue Virus-Specific Antibodies Enhance Brazilian Zika Virus Infection.

    Science.gov (United States)

    Castanha, Priscila M S; Nascimento, Eduardo J M; Braga, Cynthia; Cordeiro, Marli T; de Carvalho, Otávio V; de Mendonça, Leila R; Azevedo, Elisa A N; França, Rafael F O; Dhalia, Rafael; Marques, Ernesto T A

    2017-03-01

    Anti-Flavivirus antibodies are highly cross-reactive and may facilitate Zika virus (ZIKV) infection through the antibody-dependent enhancement (ADE) mechanism. We demonstrate that dengue-specific antibodies enhance the infection of a primary Brazilian ZIKV isolate in a FcγRII-expressing K562 cell line. In addition, we demonstrate that serum samples from dengue-immune pregnant women enhanced ZIKV infection. These findings highlight the need for epidemiological studies and animal models to further confirm the role of ADE in the development of congenital and neurological complications associated with ZIKV infections. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. [Chronic active Epstein-Barr virus infection].

    Science.gov (United States)

    Kimura, Hiroshi

    2011-12-01

    The ubiquitous Epstein-Barr virus (EBV), which establishes latency after primary infection, does not cause any symptomatic diseases as long as cellular immunity is intact. In apparently immunocompetent individuals, a chronic infection can develop, and this has been called as chronic active EBV infection (CAEBV). CAEBV is characterized by chronic or recurrent infectious mononucleosis-like symptoms, such as fever, extensive lymphadenopathy, and, hepatosplenomegaly. This disease is rare but severe with high morbidity and mortality. Recently, its pathophysiology is not an infection but a clonal expansion of EBV-infected T or natural killer NK cells. In this review, I discuss our current understanding of the pathogenesis of CAEBV and summarize its clinical features, therapies, and prognosis.

  3. Bluetongue virus infection of bovine monocytes.

    Science.gov (United States)

    Whetter, L E; Maclachlan, N J; Gebhard, D H; Heidner, H W; Moore, P F

    1989-07-01

    Cultures of adherent and non-adherent bovine blood mononuclear cells were infected with bluetongue virus (BTV) serotype 10. Production of BTV proteins in mononuclear cell cultures was detected by immune precipitation of viral proteins from [35S]methionine-labelled extracts of these cells, by immunofluorescence staining of cells using monoclonal antibodies (MAbs) to BTV proteins VP7 and NS2, and by flow cytometry with MAbs to VP2, VP7, NS1 and NS2. BTV-infected cells were most numerous in cultures of adherent mononuclear cells; infected cells were initially identified as monocytes on the basis of their morphology, and size and scatter characteristics as determined by analysis with a fluorescence-activated cell sorter (FACS). The majority of adherent mononuclear cells with these scatter characteristics were confirmed to be monocytes by FACS analysis with a MAb specific for bovine monocytes. Identification of BTV-infected adherent mononuclear cells as monocytes was further established by double immunofluorescent labelling, as infected adherent cells reacted with the MAb specific for bovine monocytes, and with another MAb specific for class II antigen. Infection of adherent mononuclear cells was also confirmed by transmission electron microscopy, as BTV virions and tubules were present in lysates of cultures of BTV-infected adherent mononuclear cells and within the cytoplasm of adherent cells. In contrast, BTV proteins were detected in few cells identified as lymphocytes on the basis of their scatter characteristics, and mean fluorescence of such cells was considerably less than that of BTV-infected monocytes. Viraemia persisted until 35 days after inoculation of a colostrum-deprived calf inoculated with BTV. Virus was isolated from blood mononuclear cells at 1 week after infection of the calf, but not thereafter. BTV infection of blood mononuclear cells was demonstrated until 9 days after inoculation by indirect immunofluorescence staining of mononuclear cells. In

  4. Hepatitis C virus infection and the brain.

    Science.gov (United States)

    Weissenborn, Karin; Tryc, Anita B; Heeren, Meike; Worthmann, Hans; Pflugrad, Henning; Berding, Georg; Bokemeyer, Martin; Tillmann, Hans L; Goldbecker, Annemarie

    2009-03-01

    There is growing evidence that hepatitis C virus (HCV)-infection may affect the brain. About half of the HCV-infected patients complain of chronic fatigue irrespective of their stage of liver disease or virus replication rate. Even after successful antiviral therapy fatigue persists in about one third of the patients. Many patients, in addition, report of deficits in attention, concentration and memory, some also of depression. Psychometric testing revealed deficits in attention and verbal learning ability as characteristic for HCV-afflicted patients with normal liver function. Magnetic resonance spectroscopic studies showed alterations of the cerebral choline, N-acetyl-aspartate, and creatine content in the basal ganglia, white matter and frontal cortex, respectively. Recently, pathologic cerebral serotonin and dopamine transporter binding and regional alterations of the cerebral glucose utilisation compatible with alterations of the dopaminergic attentional system were observed. Several studies detected HCV in brain samples or cerebro-spinal fluid. Interestingly, viral sequences in the brain often differed from those in the liver, but were closely related to those found in lymphoid tissue. Therefore, the Trojan horse hypothesis emerged: HCV-infected mononuclear blood cells enter the brain, enabling the virus to reside within the brain (probably in microglia) and to infect brain cells, especially astrocytes.

  5. Virus infection, antiviral immunity, and autoimmunity.

    Science.gov (United States)

    Getts, Daniel R; Chastain, Emily M L; Terry, Rachael L; Miller, Stephen D

    2013-09-01

    As a group of disorders, autoimmunity ranks as the third most prevalent cause of morbidity and mortality in the Western World. However, the etiology of most autoimmune diseases remains unknown. Although genetic linkage studies support a critical underlying role for genetics, the geographic distribution of these disorders as well as the low concordance rates in monozygotic twins suggest that a combination of other factors including environmental ones are involved. Virus infection is a primary factor that has been implicated in the initiation of autoimmune disease. Infection triggers a robust and usually well-coordinated immune response that is critical for viral clearance. However, in some instances, immune regulatory mechanisms may falter, culminating in the breakdown of self-tolerance, resulting in immune-mediated attack directed against both viral and self-antigens. Traditionally, cross-reactive T-cell recognition, known as molecular mimicry, as well as bystander T-cell activation, culminating in epitope spreading, have been the predominant mechanisms elucidated through which infection may culminate in an T-cell-mediated autoimmune response. However, other hypotheses including virus-induced decoy of the immune system also warrant discussion in regard to their potential for triggering autoimmunity. In this review, we discuss the mechanisms by which virus infection and antiviral immunity contribute to the development of autoimmunity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Virus elimination in acute lymphocytic choriomeningitis virus infection. Correlation with virus-specific delayed-type hypersensitivity rather than cytotoxicity

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Volkert, M; Bro-Jørgensen, K

    1983-01-01

    The immunological effector mechanism responsible for the elimination of virus in murine acute non-fatal extracranial lymphocytic choriomeningitis virus infection was studied. In this infection virus clearance is generally regarded as the result of a direct action of virus-specific cytotoxic T cells...

  7. Common and cerebrospinal immunity in pantropic virus infections

    OpenAIRE

    Dubov, A.

    2009-01-01

    We are offering and developing a hypothesis on common and transbarrier (hystohematogenous barriers) cerebrospinal immunity in pantropic virus infections. Common humoral and cellular immunity does not make improbable the penetration of virulent neurotropic viruses, such as tick-borne encephalitis pathogen, through hematoencephalitic barrier and the development of acute virus infection or virus persistence with the formation of chronic or slow infection process. Makers of specific antivirus vac...

  8. Transmission of simian immunodeficiency virus carrying multiple cytotoxic T-lymphocyte escape mutations with diminished replicative ability can result in AIDS progression in rhesus macaques.

    Science.gov (United States)

    Seki, Sayuri; Kawada, Miki; Takeda, Akiko; Igarashi, Hiroko; Sata, Tetsutaro; Matano, Tetsuro

    2008-05-01

    Cytotoxic T-lymphocyte (CTL) responses frequently select for immunodeficiency virus mutations that result in escape from CTL recognition with viral fitness costs. The replication in vivo of such viruses carrying not single but multiple escape mutations in the absence of the CTL pressure has remained undetermined. Here, we have examined the replication of simian immunodeficiency virus (SIV) with five gag mutations selected in a macaque possessing the major histocompatibility complex haplotype 90-120-Ia after its transmission into 90-120-Ia-negative macaques. Our results showed that even such a "crippled" SIV infection can result in persistent viral replication, multiple reversions, and AIDS progression.

  9. Rota virus infections: prevalence, diagnosis and prevention

    Directory of Open Access Journals (Sweden)

    Padmanabhan Vidya,

    2015-12-01

    Full Text Available Background: Diarrhoea is one of the leading causes of infant mortality. Various diagnostic methods are available and there is a need to select an ideal one. The use of Vaccines, its efficacy needs to be studied. Methods: A pubmed search, pubchem assay journal of epidemiology and infection, Google search generated results were included for review, out of 900 articles generated 111 articles are studied and were included for review. Conclusion: Molecular typing methods for viruses should aim to provide clinically and biologically useful information about field viruses, particularly with regard to virulence, viral epidemiology, and virus serotype identification. These data may be important for assessing the need for introducing rotavirus surveillance and vaccines into immunization programs in India particularly Tamilnadu.

  10. Myeloradiculopathy associated with chikungunya virus infection.

    Science.gov (United States)

    Bank, Anna M; Batra, Ayush; Colorado, Rene A; Lyons, Jennifer L

    2016-02-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is endemic to parts of Africa, South and Southeast Asia, and more recently the Caribbean. Patients typically present with fever, rash, and arthralgias, though neurologic symptoms, primarily encephalitis, have been described. We report the case of a 47-year-old woman who was clinically diagnosed with CHIKV while traveling in the Dominican Republic and presented 10 days later with left lower extremity weakness, a corresponding enhancing thoracic spinal cord lesion, and positive CHIKV serologies. She initially responded to corticosteroids, followed by relapsing symptoms and gradual clinical improvement. The time lapse between acute CHIKV infection and the onset of myelopathic sequelae suggests an immune-mediated phenomenon rather than direct activity of the virus itself. Chikungunya virus should be considered in the differential diagnosis of myelopathy in endemic areas. The progression of symptoms despite corticosteroid administration suggests more aggressive immunomodulatory therapies may be warranted at disease onset.

  11. 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.

  12. Immune Responses and Lassa Virus Infection

    Directory of Open Access Journals (Sweden)

    Sylvain Baize

    2012-11-01

    Full Text Available Lassa fever is a hemorrhagic fever endemic to West Africa and caused by Lassa virus, an Old World arenavirus. It may be fatal, but most patients recover from acute disease and some experience asymptomatic infection. The immune mechanisms associated with these different outcomes have not yet been fully elucidated, but considerable progress has recently been made, through the use of in vitro human models and nonhuman primates, the only relevant animal model that mimics the pathophysiology and immune responses induced in patients. We discuss here the roles of the various components of the innate and adaptive immune systems in Lassa virus infection and in the control of viral replication and pathogenesis.

  13. Animal Models of Varicella Zoster Virus Infection

    Directory of Open Access Journals (Sweden)

    Ilhem Messaoudi

    2013-05-01

    Full Text Available Primary infection with varicella zoster virus (VZV results in varicella (chickenpox followed by the establishment of latency in sensory ganglia. Declining T cell immunity due to aging or immune suppressive treatments can lead to VZV reactivation and the development of herpes zoster (HZ, shingles. HZ is often associated with significant morbidity and occasionally mortality in elderly and immune compromised patients. There are currently two FDA-approved vaccines for the prevention of VZV: Varivax® (for varicella and Zostavax® (for HZ. Both vaccines contain the live-attenuated Oka strain of VZV. Although highly immunogenic, a two-dose regimen is required to achieve a 99% seroconversion rate. Zostavax vaccination reduces the incidence of HZ by 51% within a 3-year period, but a significant reduction in vaccine-induced immunity is observed within the first year after vaccination. Developing more efficacious vaccines and therapeutics requires a better understanding of the host response to VZV. These studies have been hampered by the scarcity of animal models that recapitulate all aspects of VZV infections in humans. In this review, we describe different animal models of VZV infection as well as an alternative animal model that leverages the infection of Old World macaques with the highly related simian varicella virus (SVV and discuss their contributions to our understanding of pathogenesis and immunity during VZV infection.

  14. Pharmacological intervention for dengue virus infection.

    Science.gov (United States)

    Lai, Jenn-Haung; Lin, Yi-Ling; Hsieh, Shie-Liang

    2017-04-01

    Dengue virus (DENV) infection has a considerable health impact in tropical and subtropical countries worldwide. Escalation of infection rates greatly increases morbidity and mortality, most commonly from deaths due to dengue hemorrhagic fever and dengue shock syndrome. Although the development of an effective, long-lasting vaccine has been a major aim for control and prevention of DENV infection, the currently licensed vaccine has limitations and is less than satisfactory. Thus, there remains an important need to identify effective and tolerable medications for treatment of DENV-infected patients both in the early phase, to prevent progression to fatal outcomes, and to minimize deaths after patients develop severe complications. This review will address several specific points, including (1) approaches to identify anti-DENV medications, (2) recent advances in the development of potential compounds targeting DENV infection, (3) experience with clinical trials of regimens for DENV infection, (4) some available medications of potential for clinical trials against DENV infection, (5) reasons for unsuccessful outcomes and challenges of anti-DENV treatments, and (6) directions for developing or selecting better anti-DENV strategies. This review provides useful guidance for clinicians selecting drugs for DENV-infected patients with severe manifestations or potential fatal disease progression, and for basic researchers seeking to develop effective anti-DENV regimens. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Mechanisms of Zika Virus Infection and Neuropathogenesis.

    Science.gov (United States)

    Olagnier, David; Muscolini, Michela; Coyne, Carolyn B; Diamond, Michael S; Hiscott, John

    2016-08-01

    A spotlight has been focused on the mosquito-borne Zika virus (ZIKV) because of its epidemic outbreak in Brazil and Latin America, as well as the severe neurological manifestations of microcephaly and Guillain-Barré syndrome associated with infection. In this review, we discuss the recent literature on ZIKV-host interactions, including new mechanistic insight concerning the basis of ZIKV-induced neuropathogenesis.

  16. Cognitive dysfunction and hepatitis C virus infection

    OpenAIRE

    Solinas, Antonio; Piras, Maria Rita; Deplano, Angelo

    2015-01-01

    Cognitive dysfunction in patients with chronic hepatitis C virus (HCV) infection is a distinct form of minimal hepatic encephalopathy (MHE). In fact, the majority of HCV-positive patients, irrespective of the grading of liver fibrosis, display alterations of verbal learning, attention, executive function, and memory when they are evaluated by suitable neuropsychological tests. Similarities between the cognitive dysfunction of HCV patients and MHE of patients with different etiologies are uncl...

  17. Influenza A virus infections in swine: pathogenesis and diagnosis.

    Science.gov (United States)

    Janke, B H

    2014-03-01

    Influenza has been recognized as a respiratory disease in swine since its first appearance concurrent with the 1918 "Spanish flu" human pandemic. All influenza viruses of significance in swine are type A, subtype H1N1, H1N2, or H3N2 viruses. Influenza viruses infect epithelial cells lining the surface of the respiratory tract, inducing prominent necrotizing bronchitis and bronchiolitis and variable interstitial pneumonia. Cell death is due to direct virus infection and to insult directed by leukocytes and cytokines of the innate immune system. The most virulent viruses consistently express the following characteristics of infection: (1) higher or more prolonged virus replication, (2) excessive cytokine induction, and (3) replication in the lower respiratory tract. Nearly all the viral proteins contribute to virulence. Pigs are susceptible to infection with both human and avian viruses, which often results in gene reassortment between these viruses and endemic swine viruses. The receptors on the epithelial cells lining the respiratory tract are major determinants of infection by influenza viruses from other hosts. The polymerases, especially PB2, also influence cross-species infection. Methods of diagnosis and characterization of influenza viruses that infect swine have improved over the years, driven both by the availability of new technologies and by the necessity of keeping up with changes in the virus. Testing of oral fluids from pigs for virus and antibody is a recent development that allows efficient sampling of large numbers of animals.

  18. 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.

  19. 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

  20. Laboratory Diagnosis of Zika Virus Infection.

    Science.gov (United States)

    Landry, Marie Louise; St George, Kirsten

    2017-01-01

    -The rapid and accurate diagnosis of Zika virus infection is an international priority. -To review current recommendations, methods, limitations, and priorities for Zika virus testing. -Sources include published literature, public health recommendations, laboratory procedures, and testing experience. -Until recently, the laboratory diagnosis of Zika infection was confined to public health or research laboratories that prepared their own reagents, and test capacity has been limited. Furthermore, Zika cross-reacts serologically with other flaviviruses, such as dengue, West Nile, and yellow fever. Current or past infection, or even vaccination with another flavivirus, will often cause false-positive or uninterpretable Zika serology results. Detection of viral RNA during acute infection using nucleic acid amplification tests provides more specific results, and a number of commercial nucleic acid amplification tests have received emergency use authorization. In addition to serum, testing of whole blood and urine is recommended because of the higher vial loads and longer duration of shedding. However, nucleic acid amplification testing has limited utility because many patients are asymptomatic or present for testing after the brief period of Zika shedding has passed. Thus, the greatest need and most difficult challenge is development of accurate antibody tests for the diagnosis of recent Zika infection. Research is urgently needed to identify Zika virus epitopes that do not cross-react with other flavivirus antigens. New information is emerging at a rapid pace and, with ongoing public-private and international collaborations and government support, it is hoped that rapid progress will be made in developing robust and widely applicable diagnostic tools.

  1. Distinct Patterns of Tryptophan Maintenance in Tissues during Kynurenine Pathway Activation in Simian Immunodeficiency Virus-Infected Macaques

    Directory of Open Access Journals (Sweden)

    Julia L Drewes

    2016-12-01

    Full Text Available Induction of the kynurenine pathway (KP of tryptophan catabolism has been proposed to contribute to T cell dysfunction during human/simian immunodeficiency virus (HIV/SIV infection via depletion of local tryptophan levels and production of immunomodulatory KP metabolites. However, while changes in tryptophan and KP metabolites have been observed in plasma, their levels in lymphoid tissues and levels of enzymes downstream of indoleamine 2,3-dioxygenase (IDO1 have been relatively unexplored. We used our SIV-infected pigtailed macaque model to analyze longitudinal changes in KP metabolites and enzymes by gas chromatography/mass spectrometry and NanoString nCounter gene expression analysis, respectively, in spleen and blood compared to changes previously established in brain and CSF. We found that tryptophan levels were remarkably stable in tissue sites despite robust depletion in the circulating plasma and CSF. We also demonstrated that intracellular tryptophan reserves were maintained in cultured cells even in the presence of depleted extracellular tryptophan levels. Kynurenine, 3-hydroxykynurenine, quinolinic acid, and the KP enzymes all displayed highly divergent patterns in the sites examined, though IDO1 expression always correlated with local kynurenine/tryptophan ratios. Finally, we demonstrated by FACS that myeloid dendritic cells (mDCs and cells of monocytic lineage were the highest producers of IDO1 in chronically infected spleens. Overall our study reveals insights into the tissue-specific regulation of KP enzymes and metabolites and, in particular, highlights the multiple mechanisms by which cells and tissues seek to prevent TRP starvation during inflammation.

  2. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel.

    Directory of Open Access Journals (Sweden)

    Martin Cranage

    2008-08-01

    Full Text Available The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT inhibitor tenofovir (PMPA, 9-[(R-2-(phosphonomethoxy propyl] adenine monohydrate, a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV in a well-established and standardised macaque model.A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50 of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC, quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA load by sensitive quantitative competitive (qc RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from infection (n = 6 or had

  3. Increased monocyte turnover from bone marrow correlates with severity of SIV encephalitis and CD163 levels in plasma.

    Directory of Open Access Journals (Sweden)

    Tricia H Burdo

    2010-04-01

    Full Text Available Cells of the myeloid lineage are significant targets for human immunodeficiency virus (HIV in humans and simian immunodeficiency virus (SIV in monkeys. Monocytes play critical roles in innate and adaptive immunity during inflammation. We hypothesize that specific subsets of monocytes expand with AIDS and drive central nervous system (CNS disease. Additionally, there may be expansion of cells from the bone marrow through blood with subsequent macrophage accumulation in tissues driving pathogenesis. To identify monocytes that recently emigrated from bone marrow, we used 5-bromo-2'-deoxyuridine (BrdU labeling in a longitudinal study of SIV-infected CD8+ T lymphocyte depleted macaques. Monocyte expansion and kinetics in blood was assessed and newly migrated monocyte/macrophages were identified within the CNS. Five animals developed rapid AIDS with differing severity of SIVE. The percentages of BrdU+ monocytes in these animals increased dramatically, early after infection, peaking at necropsy where the percentage of BrdU+ monocytes correlated with the severity of SIVE. Early analysis revealed changes in the percentages of BrdU+ monocytes between slow and rapid progressors as early as 8 days and consistently by 27 days post infection. Soluble CD163 (sCD163 in plasma correlated with the percentage of BrdU+ monocytes in blood, demonstrating a relationship between monocyte activation and expansion with disease. BrdU+ monocytes/macrophages were found within perivascular spaces and SIVE lesions. The majority (80-90% of the BrdU+ cells were Mac387+ that were not productively infected. There was a minor population of CD68+BrdU+ cells (<10%, very few of which were infected (<1% of total BrdU+ cells. Our results suggest that an increased rate of monocyte recruitment from bone marrow into the blood correlates with rapid progression to AIDS, and the magnitude of BrdU+ monocytes correlates with the severity of SIVE.

  4. Hepatitis E Virus (HEV) Infection in Ireland

    LENUS (Irish Health Repository)

    Hickey, C

    2016-09-01

    Hepatitis E virus (HEV) is a single stranded RNA virus causing infection worldwide. In developing countries HEV genotypes 1 and 2 spread faeco-orally via water. Recently, infections with HEV have been detected in Europe and North America in patients with no travel history. These are food-borne HEV genotypes 3 and 4, a pig-associated zoonosis. Most infections are asymptomatic but morbidity and chronic infection may occur with prior liver disease or immunosuppression. International seroprevalence rates vary and with improved diagnostics have increased. To determine the current prevalence in this region we studied anonymised serum samples submitted in 2015 for routine testing. We detected anti-HEV IgG in 16\\/198 (8%) individuals, highest rate in 40-59 year olds (43.8%). This is higher than reported for the same region in 1995 (0.4%) using a previous generation assay. This study provides evidence of HEV circulation in Ireland and reinforces the need for ongoing surveillance.

  5. The epidemiology of respiratory syncytial virus (RSV) infections in ...

    African Journals Online (AJOL)

    South African' or 'children' and 'respiratory syncytial virus' or 'acute respiratory tract infections' as text words were retrieved. We analysed the data on respiratory virus activity from January 1990 to June 1996. Data were obtained from the National ...

  6. Clinical studies on hepatitis B, C, and E virus infection

    NARCIS (Netherlands)

    Willemse, S.B.

    2017-01-01

    Chronic viral hepatitis is a major cause of liver-related morbidity and mortality. This thesis describes clinical aspects of hepatitis B, C, and E virus infection. Part I focuses on hepatitis B virus (HBV) infection. This part describes immune responses of patients with acute HBV-infection,

  7. KINETIC PROFILE OF INFLUENZA VIRUS INFECTION IN THREE RAT STRAINS

    Science.gov (United States)

    AbstractInfluenza infection is a respiratory disease of viral origin that can cause major epidemics in man. The influenza virus infects and damages epithelial cells of the respiratory tract and causes pneumonia. Lung lesions of mice infected with influenza virus resembl...

  8. Epitope-specific CD8+ T cell kinetics rather than viral variability determine the timing of immune escape in simian immunodeficiency virus infection.

    Science.gov (United States)

    Martyushev, Alexey P; Petravic, Janka; Grimm, Andrew J; Alinejad-Rokny, Hamid; Gooneratne, Shayarana L; Reece, Jeanette C; Cromer, Deborah; Kent, Stephen J; Davenport, Miles P

    2015-05-01

    CD8(+) T cells are important for the control of chronic HIV infection. However, the virus rapidly acquires "escape mutations" that reduce CD8(+) T cell recognition and viral control. The timing of when immune escape occurs at a given epitope varies widely among patients and also among different epitopes within a patient. The strength of the CD8(+) T cell response, as well as mutation rates, patterns of particular amino acids undergoing escape, and growth rates of escape mutants, may affect when escape occurs. In this study, we analyze the epitope-specific CD8(+) T cells in 25 SIV-infected pigtail macaques responding to three SIV epitopes. Two epitopes showed a variable escape pattern and one had a highly monomorphic escape pattern. Despite very different patterns, immune escape occurs with a similar delay of on average 18 d after the epitope-specific CD8(+) T cells reach 0.5% of total CD8(+) T cells. We find that the most delayed escape occurs in one of the highly variable epitopes, and that this is associated with a delay in the epitope-specific CD8(+) T cells responding to this epitope. When we analyzed the kinetics of immune escape, we found that multiple escape mutants emerge simultaneously during the escape, implying that a diverse population of potential escape mutants is present during immune selection. Our results suggest that the conservation or variability of an epitope does not appear to affect the timing of immune escape in SIV. Instead, timing of escape is largely determined by the kinetics of epitope-specific CD8(+) T cells. Copyright © 2015 by The American Association of Immunologists, Inc.

  9. Congenital Zika Virus Infection: Beyond Neonatal Microcephaly.

    Science.gov (United States)

    Melo, Adriana Suely de Oliveira; Aguiar, Renato Santana; Amorim, Melania Maria Ramos; Arruda, Monica B; Melo, Fabiana de Oliveira; Ribeiro, Suelem Taís Clementino; Batista, Alba Gean Medeiros; Ferreira, Thales; Dos Santos, Mayra Pereira; Sampaio, Virgínia Vilar; Moura, Sarah Rogéria Martins; Rabello, Luciana Portela; Gonzaga, Clarissa Emanuelle; Malinger, Gustavo; Ximenes, Renato; de Oliveira-Szejnfeld, Patricia Soares; Tovar-Moll, Fernanda; Chimelli, Leila; Silveira, Paola Paz; Delvechio, Rodrigo; Higa, Luiza; Campanati, Loraine; Nogueira, Rita M R; Filippis, Ana Maria Bispo; Szejnfeld, Jacob; Voloch, Carolina Moreira; Ferreira, Orlando C; Brindeiro, Rodrigo M; Tanuri, Amilcar

    2016-12-01

    Recent studies have reported an increase in the number of fetuses and neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV) during pregnancy. To our knowledge, most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects. To describe the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurological damage associated with ZIKV infection in Brazil. We observed 11 infants with congenital ZIKV infection from gestation to 6 months in the state of Paraíba, Brazil. Ten of 11 women included in this study presented with symptoms of ZIKV infection during the first half of pregnancy, and all 11 had laboratory evidence of the infection in several tissues by serology or polymerase chain reaction. Brain damage was confirmed through intrauterine ultrasonography and was complemented by magnetic resonance imaging. Histopathological analysis was performed on the placenta and brain tissue from infants who died. The ZIKV genome was investigated in several tissues and sequenced for further phylogenetic analysis. Description of the major lesions caused by ZIKV congenital infection. Of the 11 infants, 7 (63.6%) were female, and the median (SD) maternal age at delivery was 25 (6) years. Three of 11 neonates died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic perimeter at birth was 31 (3) cm, a value lower than the limit to consider a microcephaly case. In all patients, neurological impairments were identified, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence (ie, arthrogryposis). Results of limited testing for other causes of microcephaly, such as genetic disorders and viral and bacterial infections, were negative, and the ZIKV genome was found in both maternal and neonatal tissues (eg, amniotic fluid, cord blood, placenta, and

  10. Co-infections with Chikungunya and Dengue Viruses, Guatemala, 2015

    National Research Council Canada - National Science Library

    Edwards, Thomas; Signor, Leticia del Carmen Castillo; Williams, Christopher; Donis, Evelin; Cuevas, Luis E; Adams, Emily R

    2016-01-01

    ... infections and 635,000 CHIKV infections were reported in this region in 2015 (4,5). However, details of the frequency of co-infection are lacking (1), although a recent study involving 173 samples from Nicaragua that were positive for either virus found a co-infection rate of 22% (6). Co-infections might be frequently missed by surveillance ...

  11. Additive interactions of unrelated viruses in mixed infections of cowpea.

    Directory of Open Access Journals (Sweden)

    Imade Yolanda Nsa

    2015-10-01

    Full Text Available This study was carried out to determine the effects of single infections and co-infections of three unrelated viruses on three cowpea cultivars (one commercial cowpea cultivar White and 2 IITA lines; IT81D-985 and TVu76. The plants were inoculated with Cowpea aphid-borne mosaic virus (CABMV, genus Potyvirus, Cowpea mottle virus (CMeV, genus Carmovirus and Southern bean mosaic virus (SBMV, genus Sobemovirus singly and in mixture (double and triple at 10, 20 and 30 days after planting (DAP. The treated plants were assessed for susceptibility to the viruses, growth and yield. In all cases of infection, early inoculation resulted in higher disease severity compared with late infection. The virus treated cowpea plants were relatively shorter than buffer inoculated control plants except the IT81D-985 plants that were taller and produced more foliage. Single infections by CABMV, CMeV and SBMV led to a complete loss of seeds in the three cowpea cultivars at 10DAP; only cultivar White produced some seeds at 30DAP. Double and triple virus infections led to a total loss of seeds in all three cowpea cultivars. None of the virus infected IITA lines produced any seeds except IT81D-985 plants co-infected with CABMV and SBMV at 30DAP with a reduction of 80%. Overall, the commercial cultivar White was the least susceptible to the virus treatments and produced the most yield (flowers, pods and seeds. CABMV was the most aggressive of these viruses and early single inoculations with this virus resulted in the premature death of some of the seedlings. The presence of the Potyvirus, CABMV in the double virus infections did not appear to increase disease severity or yield loss. There was no strong evidence for synergistic interactions between the viruses in the double virus mixtures.

  12. Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection.

    Science.gov (United States)

    Collins, Matthew H; McGowan, Eileen; Jadi, Ramesh; Young, Ellen; Lopez, Cesar A; Baric, Ralph S; Lazear, Helen M; de Silva, Aravinda M

    2017-05-01

    Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus-specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity.

  13. Rota virus infections: prevalence, diagnosis and prevention

    National Research Council Canada - National Science Library

    Vidya, Padmanabhan; Ponnambalam, Arun; Gunasekeran, Palani; Arunagiri, Kavitha; Sambasivam, Mohana; Krishnasami, Kaveri

    2015-01-01

    ...: Molecular typing methods for viruses should aim to provide clinically and biologically useful information about field viruses, particularly with regard to virulence, viral epidemiology, and virus...

  14. Animal Models of Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Eva Harris

    2012-01-01

    Full Text Available The development of animal models of dengue virus (DENV infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines.

  15. Animal models of dengue virus infection.

    Science.gov (United States)

    Zompi, Simona; Harris, Eva

    2012-01-01

    The development of animal models of dengue virus (DENV) infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs) can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the 'vascular-leak' syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines.

  16. Animal models of respiratory syncytial virus infection.

    Science.gov (United States)

    Taylor, Geraldine

    2017-01-11

    Human respiratory syncytial virus (hRSV) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. There is no licensed hRSV vaccine or effective therapeutic agent. However, there are a growing number of hRSV vaccine candidates that have been developed targeting different populations at risk of hRSV infection. Animal models of hRSV play an important role in the preclinical testing of hRSV vaccine candidates and although many have shown efficacy in preclinical studies, few have progressed to clinical trials or they have had only limited success. This is, at least in part, due to the lack of animal models that fully recapitulate the pathogenesis of hRSV infection in humans. This review summarises the strengths and limitations of animal models of hRSV, which include those in which hRSV is used to infect non-human mammalian hosts, and those in which non-human pneumoviruses, such as bovine (b)RSV and pneumonia virus of mice (PVM) are studied in their natural host. Apart from chimpanzees, other non-human primates (NHP) are only semi-permissive for hRSV replication and experimental infection with large doses of virus result in little or no clinical signs of disease, and generally only mild pulmonary pathology. Other animal models such as cotton rats, mice, ferrets, guinea pigs, hamsters, chinchillas, and neonatal lambs are also only semi-permissive for hRSV. Nevertheless, mice and cotton rats have been of value in the development of monoclonal antibody prophylaxis for infants at high risk of severe hRSV infection and have provided insights into mechanisms of immunity to and pathogenesis of hRSV. However, the extent to which they predict hRSV vaccine efficacy and safety is unclear and several hRSV vaccine candidates that are completely protective in rodent models are poorly effective in chimpanzees and other NHP, such as African Green monkeys. Furthermore

  17. Plant RNA binding proteins for control of RNA virus infection

    Directory of Open Access Journals (Sweden)

    Sung Un eHuh

    2013-12-01

    Full Text Available Plant RNA viruses have effective strategies to infect host plants through either direct or indirect interactions with various host proteins, thus suppressing the host immune system. When plant RNA viruses enter host cells exposed RNAs of viruses are recognized by the host immune system through processes such as siRNA-dependent silencing. Interestingly, some host RNA binding proteins have been involved in the inhibition of RNA virus replication, movement, and translation through RNA-specific binding. Host plants intensively use RNA binding proteins for defense against viral infections in nature. In this mini review, we will summarize the function of some host RNA binding proteins which act in a sequence-specific binding manner to the infecting virus RNA. It is important to understand how plants effectively suppresses RNA virus infections via RNA binding proteins, and this defense system can be potentially developed as a synthetic virus defense strategy for use in crop engineering.

  18. Rota virus infections: prevalence, diagnosis and prevention

    OpenAIRE

    Padmanabhan Vidya,; Arun Ponnambalam,; Palani Gunasekeran,; Kavitha Arunagiri,; Mohana Sambasivam; Kaveri Krishnasami

    2015-01-01

    Background: Diarrhoea is one of the leading causes of infant mortality. Various diagnostic methods are available and there is a need to select an ideal one. The use of Vaccines, its efficacy needs to be studied. Methods: A pubmed search, pubchem assay journal of epidemiology and infection, Google search generated results were included for review, out of 900 articles generated 111 articles are studied and were included for review. Conclusion: Molecular typing methods for viruses should aim to ...

  19. The ecology of viruses that infect eukaryotic algae.

    Science.gov (United States)

    Short, Steven M

    2012-09-01

    Because viruses of eukaryotic algae are incredibly diverse, sweeping generalizations about their ecology are rare. These obligate parasites infect a range of algae and their diversity can be illustrated by considering that isolates range from small particles with ssRNA genomes to much larger particles with 560 kb dsDNA genomes. Molecular research has also provided clues about the extent of their diversity especially considering that genetic signatures of algal viruses in the environment rarely match cultivated viruses. One general concept in algal virus ecology that has emerged is that algal viruses are very host specific and most infect only certain strains of their hosts; with the exception of viruses of brown algae, evidence for interspecies infectivity is lacking. Although some host-virus systems behave with boom-bust oscillations, complex patterns of intraspecies infectivity can lead to host-virus coexistence obfuscating the role of viruses in host population dynamics. Within the framework of population dynamics, host density dependence is an important phenomenon that influences virus abundances in nature. Variable burst sizes of different viruses also influence their abundances and permit speculations about different life strategies, but as exceptions are common in algal virus ecology, life strategy generalizations may not be broadly applicable. Gaps in knowledge of virus seasonality and persistence are beginning to close and investigations of environmental reservoirs and virus resilience may answer questions about virus inter-annual recurrences. Studies of algal mortality have shown that viruses are often important agents of mortality reinforcing notions about their ecological relevance, while observations of the surprising ways viruses interact with their hosts highlight the immaturity of our understanding. Considering that just two decades ago algal viruses were hardly acknowledged, recent progress affords the optimistic perspective that future studies

  20. Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys

    NARCIS (Netherlands)

    Liu, J.; O'Brien, K.L.; Lynch, D.M.; Simmons, N.L.; Porte, A. La; Riggs, A.M.; Abbink, P.; Coffey, R.T.; Grandpre, L.E.; Seaman, M.S.; Landucci, G.; Forthal, D.N.; Montefiori, D.C.; Carville, A.; Mansfield, K.G.; Havenga, M.J.; Pau, M.G.; Goudsmit, J.; Barouch, D.H.

    2009-01-01

    A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or

  1. Zika virus infections in pregnancy: epidemics and case management

    Directory of Open Access Journals (Sweden)

    Fatih sahiner

    2016-03-01

    Full Text Available Zika virus is an RNA virus belonging to the Flaviviridae family, and is primarily transmitted by Aedes mosquitoes. Only a small number of cases had been described until 2007 when the first major Zika virus outbreak occurred on Yap Island, Micronesia. Approximately 80% of people infected with Zika virus do not exhibit any symptoms. Symptomatic infections are generally moderate and characterized by acute onset of fever, maculopapular rash, arthralgia, or conjunctivitis. The virus has recently attracted a broad interest due to the emerging cases of microcephaly that are possibly associated with mothers infected by the Zika virus during pregnancy, and the regional increases in the incidence of Guillain-Barre syndrome during the epidemic periods. Although the relationship between Zika virus infection and these abnormalities is not obviously understood yet, Zika virus testing is recommended for infants with microcephaly or intracranial calcifications whose mothers were potentially infected with the Zika virus during pregnancy. Every day, new reports are being published about the outbreaks associated with this virus; nevertheless, no new cases of this virus have been reported in Turkey. Despite this, we cannot currently exclude the possibility of the encounter with the virus because of the presence of Aedes mosquitoes, which are responsible for the spread of the virus, are prevalent in Turkey, and an increasing number of travel-related cases are being reported from different countries. In the light of the current knowledge on this virus, this review aims to discuss the course of Zika virus infections in detail, especially congenital infection, and presenting current information about the case management and preventive measures. [Cukurova Med J 2016; 41(1.000: 143-151

  2. Evaluation of the zoonotic potential of a novel reassortant H1N2 swine influenza virus with gene constellation derived from multiple viral sources.

    Science.gov (United States)

    Lee, Jee Hoon; Pascua, Philippe Noriel Q; Decano, Arun G; Kim, Se Mi; Park, Su-Jin; Kwon, Hyeok-Il; Kim, Eun-Ha; Kim, Young-Il; Kim, HyongKyu; Kim, Seok-Yong; Song, Min-Suk; Jang, Hyung-Kwan; Park, Bong Kyun; Choi, Young Ki

    2015-08-01

    In 2011-2012, contemporary North American-like H3N2 swine influenza viruses (SIVs) possessing the 2009 pandemic H1N1 matrix gene (H3N2pM-like virus) were detected in domestic pigs of South Korea where H1N2 SIV strains are endemic. More recently, we isolated novel reassortant H1N2 SIVs bearing the Eurasian avian-like swine H1-like hemagglutinin and Korean swine H1N2-like neuraminidase in the internal gene backbone of the H3N2pM-like virus. In the present study, we clearly provide evidence on the genetic origins of the novel H1N2 SIVs virus through genetic and phylogenetic analyses. In vitro studies demonstrated that, in comparison with a pre-existing 2012 Korean H1N2 SIV [A/swine/Korea/CY03-11/2012 (CY03-11/2012)], the 2013 novel reassortant H1N2 isolate [A/swine/Korea/CY0423/2013 (CY0423-12/2013)] replicated more efficiently in differentiated primary human bronchial epithelial cells. The CY0423-12/2013 virus induced higher viral titers than the CY03-11/2012 virus in the lungs and nasal turbinates of infected mice and nasal wash samples of ferrets. Moreover, the 2013 H1N2 reassortant, but not the intact 2012 H1N2 virus, was transmissible to naïve contact ferrets via respiratory-droplets. Noting that the viral precursors have the ability to infect humans, our findings highlight the potential threat of a novel reassortant H1N2 SIV to public health and underscore the need to further strengthen influenza surveillance strategies worldwide, including swine populations. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Oxidative stress in Mayaro virus infection.

    Science.gov (United States)

    Camini, Fernanda Caetano; da Silva Caetano, Camila Carla; Almeida, Letícia Trindade; da Costa Guerra, Joyce Ferreira; de Mello Silva, Breno; de Queiroz Silva, Silvana; de Magalhães, José Carlos; de Brito Magalhães, Cintia Lopes

    2017-05-15

    Mayaro virus (MAYV) is a neglected tropical arbovirus that causes a febrile syndrome that is sometimes accompanied by incapacitating arthritis/arthralgia. The pathogenesis of MAYV has not been completely defined and oxidative stress mediated by an increase in reactive oxygen species (ROS) and/or depletion of antioxidant defences has been found to contribute to several aspects of viral disease. To investigate whether MAYV induced oxidative stress in host cells, we monitored ROS production, oxidative stress markers and antioxidant defences at different time points after infection. Our results show that MAYV induced significant oxidative stress in infected HepG2 cells, as indicated by the increase of malondialdehyde (MDA) and protein carbonyl levels, and by a significant decrease of the reduced versus oxidized glutathione (GSH/GSSG) ratio. Generally, MAYV-infected HepG2 cells also showed an increase in antioxidant defences. We observed an increase in the superoxide dismutase (SOD) and catalase (CAT) activities and the total glutathione content. To determine whether similar effects occurred in other cell types, we evaluated the ROS, MDA and SOD activity levels in J774 cells after MAYV infection. Similar to our observations in HepG2 cells, the J774 cells showed an increase in ROS, MDA and total SOD activity following MAYV infection. Thus, since the cellular redox environment is influenced by the production and removal of ROS, we hypothesize that the overproduction of ROS was responsible for the oxidative stress in response to the MAYV infection despite the increase in the antioxidant status. This study is the first report on the involvement of oxidative stress during MAYV infection. Collectively, our data shed light on some mechanisms that are operational in host cells following exposure to MAYV. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Polysulfonate suramin inhibits Zika virus infection.

    Science.gov (United States)

    Tan, Chee Wah; Sam, I-Ching; Chong, Wei Lim; Lee, Vannajan Sanghiran; Chan, Yoke Fun

    2017-07-01

    Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log 10  PFU viral reduction with IC 50 value of ∼2.5-5 μg/ml (1.93 μM-3.85 μM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Hepatitis B virus infection in Indonesia.

    Science.gov (United States)

    Yano, Yoshihiko; Utsumi, Takako; Lusida, Maria Inge; Hayashi, Yoshitake

    2015-10-14

    Approximately 240 million people are chronically infected with hepatitis B virus (HBV), 75% of whom reside in Asia. Approximately 600000 of infected patients die each year due to HBV-related diseases or hepatocellular carcinoma (HCC). The endemicity of hepatitis surface antigen in Indonesia is intermediate to high with a geographical difference. The risk of HBV infection is high in hemodialysis (HD) patients, men having sex with men, and health care workers. Occult HBV infection has been detected in various groups such as blood donors, HD patients, and HIV-infected individuals and children. The most common HBV subgenotype in Indonesia is B3 followed by C1. Various novel subgenotypes of HBV have been identified throughout Indonesia, with the novel HBV subgenotypes C6-C16 and D6 being successfully isolated. Although a number of HBV subgenotypes have been discovered in Indonesia, genotype-related pathogenicity has not yet been elucidated in detail. Therefore, genotype-related differences in the prognosis of liver disease and their effects on treatments need to be determined. A previous study conducted in Indonesia revealed that hepatic steatosis was associated with disease progression. Pre-S2 mutations and mutations at C1638T and T1753V in HBV/B3 have been associated with advanced liver diseases including HCC. However, drug resistance to lamivudine, which is prominent in Indonesia, remains obscure. Although the number of studies on HBV in Indonesia has been increasing, adequate databases on HBV infection are limited. We herein provided an overview of the epidemiology and clinical characteristics of HBV infection in Indonesia.

  6. Perinatal Chicken Pox (Varicella Zoster Virus Infection

    Directory of Open Access Journals (Sweden)

    Ali Annagur

    2013-04-01

    Full Text Available Chickenpox is due to infection with the varicella zoster virus (VZV, a human alphaherpervirus found worldwide. Classically, the cinical disease is a febrile illness with a pruritic vesicular rash. Maternal chickenpox between 5 days before delivery to 2 days after delivery (perinatal varicella can cause severe and even fatal illness in the newborn. A 7-day old girl baby presented on day 4 of postnatal with the complaints of widespread vesicular rash and non-suckling. Mother of the baby also had a similar eruption four day prior to delivery, which was clinically characteristic of varicella. Considering history and clinical presentation, a diagnosis of perinatal chickenpox was considered and the baby was treated with acyclovir which she responded and recovered. Herein, the clinical feasures and treatment of chickenpox infection in the perinatal period have been emphasized with this case report. [Cukurova Med J 2013; 38(2.000: 311-314

  7. Encephalomyocarditis virus infection in an Italian zoo

    Directory of Open Access Journals (Sweden)

    Pascotto Ernesto

    2010-03-01

    Full Text Available Abstract A fatal Encephalomyocarditis virus (EMCV infection epidemic involving fifteen primates occurred between October 2006 and February 2007 at the Natura Viva Zoo. This large open-field zoo park located near Lake Garda in Northern Italy hosts one thousand animals belonging to one hundred and fifty different species, including various lemur species. This lemur collection is the most relevant and rich in Italy. A second outbreak between September and November 2008 involved three lemurs. In all cases, the clinical signs were sudden deaths generally without any evident symptoms or only with mild unspecific clinical signs. Gross pathologic changes were characterized by myocarditis (diffuse or focal pallor of the myocardium, pulmonary congestion, emphysema, oedema and thoracic fluid. The EMCV was isolated and recognized as the causative agent of both outbreaks. The first outbreak in particular was associated with a rodent plague, confirming that rats are an important risk factor for the occurrence of the EMCV infection.

  8. 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...

  9. Diagnosis and Management of Paediatric Hepatitis C Virus Infection ...

    African Journals Online (AJOL)

    Diagnosis and Management of Paediatric Hepatitis C Virus Infection. ... Without accurate diagnosis and follow up, these children cannot be offered optimal care, and are at risk ... Keywords:Acute infective hepatitis;Catalase; LiverFunction Tests ...

  10. Response of cattle persistently infected with bovine virus diarrhoea virus to bovine leukosis virus.

    Science.gov (United States)

    Roberts, D H; Lucas, M H; Wibberley, G; Westcott, D

    1988-03-26

    Six cattle persistently infected with bovine virus diarrhoea virus (BVDV) and seronegative, and two control, virus negative seropositive cattle were inoculated with lymphocytes infected with bovine leukosis virus (BLV). The two controls produced a normal immune response to BLV, developing antibodies at four and five weeks after inoculation. Two of the six cattle persistently infected with BVDV developed a strong antibody response by six weeks after inoculation with BLV. Four developed a depressed response to BLV, characterised in three by a 'hooking' reaction in the immunodiffusion test which persisted in successive bleedings but was interspersed occasionally by a weak positive reaction. In one of these animals, a series of 'hooking' reactions was followed by a number of negative results. The fourth animal remained serologically negative until 16 weeks after inoculation when a 'hooking' reaction was observed followed by a series of negative results. BLV was isolated from all the cattle persistently infected with BVDV at 42 or 58 weeks after inoculation regardless of whether the serum samples gave negative, 'hooking', weak positive or positive reactions in the immunodiffusion test. BLV was consistently isolated from the nasal secretions of a steer which was BVDV negative but seropositive. The possibility of decreased immune responsiveness to BLV in animals persistently infected with BVDV should be considered when formulating regulations governing the testing of animals for freedom from BLV.

  11. Honey Bee Infecting Lake Sinai Viruses

    Directory of Open Access Journals (Sweden)

    Katie F. Daughenbaugh

    2015-06-01

    Full Text Available Honey bees are critical pollinators of important agricultural crops. Recently, high annual losses of honey bee colonies have prompted further investigation of honey bee infecting viruses. To better characterize the recently discovered and very prevalent Lake Sinai virus (LSV group, we sequenced currently circulating LSVs, performed phylogenetic analysis, and obtained images of LSV2. Sequence analysis resulted in extension of the LSV1 and LSV2 genomes, the first detection of LSV4 in the US, and the discovery of LSV6 and LSV7. We detected LSV1 and LSV2 in the Varroa destructor mite, and determined that a large proportion of LSV2 is found in the honey bee gut, suggesting that vector-mediated, food-associated, and/or fecal-oral routes may be important for LSV dissemination. Pathogen-specific quantitative PCR data, obtained from samples collected during a small-scale monitoring project, revealed that LSV2, LSV1, Black queen cell virus (BQCV, and Nosema ceranae were more abundant in weak colonies than strong colonies within this sample cohort. Together, these results enhance our current understanding of LSVs and illustrate the importance of future studies aimed at investigating the role of LSVs and other pathogens on honey bee health at both the individual and colony levels.

  12. Honey Bee Infecting Lake Sinai Viruses.

    Science.gov (United States)

    Daughenbaugh, Katie F; Martin, Madison; Brutscher, Laura M; Cavigli, Ian; Garcia, Emma; Lavin, Matt; Flenniken, Michelle L

    2015-06-23

    Honey bees are critical pollinators of important agricultural crops. Recently, high annual losses of honey bee colonies have prompted further investigation of honey bee infecting viruses. To better characterize the recently discovered and very prevalent Lake Sinai virus (LSV) group, we sequenced currently circulating LSVs, performed phylogenetic analysis, and obtained images of LSV2. Sequence analysis resulted in extension of the LSV1 and LSV2 genomes, the first detection of LSV4 in the US, and the discovery of LSV6 and LSV7. We detected LSV1 and LSV2 in the Varroa destructor mite, and determined that a large proportion of LSV2 is found in the honey bee gut, suggesting that vector-mediated, food-associated, and/or fecal-oral routes may be important for LSV dissemination. Pathogen-specific quantitative PCR data, obtained from samples collected during a small-scale monitoring project, revealed that LSV2, LSV1, Black queen cell virus (BQCV), and Nosema ceranae were more abundant in weak colonies than strong colonies within this sample cohort. Together, these results enhance our current understanding of LSVs and illustrate the importance of future studies aimed at investigating the role of LSVs and other pathogens on honey bee health at both the individual and colony levels.

  13. Spatiotemporal Dynamics of Virus Infection Spreading in Tissues

    Science.gov (United States)

    Meyerhans, Andreas; Bessonov, Nickolai; Trofimchuk, Sergei; Volpert, Vitaly

    2016-01-01

    Virus spreading in tissues is determined by virus transport, virus multiplication in host cells and the virus-induced immune response. Cytotoxic T cells remove infected cells with a rate determined by the infection level. The intensity of the immune response has a bell-shaped dependence on the concentration of virus, i.e., it increases at low and decays at high infection levels. A combination of these effects and a time delay in the immune response determine the development of virus infection in tissues like spleen or lymph nodes. The mathematical model described in this work consists of reaction-diffusion equations with a delay. It shows that the different regimes of infection spreading like the establishment of a low level infection, a high level infection or a transition between both are determined by the initial virus load and by the intensity of the immune response. The dynamics of the model solutions include simple and composed waves, and periodic and aperiodic oscillations. The results of analytical and numerical studies of the model provide a systematic basis for a quantitative understanding and interpretation of the determinants of the infection process in target organs and tissues from the image-derived data as well as of the spatiotemporal mechanisms of viral disease pathogenesis, and have direct implications for a biopsy-based medical testing of the chronic infection processes caused by viruses, e.g. HIV, HCV and HBV. PMID:27997613

  14. Encephalomyocarditis virus infections in an Australian zoo.

    Science.gov (United States)

    Reddacliff, L A; Kirkland, P D; Hartley, W J; Reece, R L

    1997-06-01

    Fatal encephalomyocarditis virus (EMCV) infections in a ring-tailed lemur (Lemur catta), a squirrel monkey (Saimiri sciureus), three mandrills (Mandrillus sphinx), a chimpanzee (Pan troglodytes), a pygmy hippopotamus (Choeropsis liberiensis), and two Goodfellows tree kangaroos (Dendrolagus goodfellowi) occurred at Taronga Zoo. This is the first description of EMCV in a zoological collection outside of the United States. Regardless of species, the most common clinical presentation was sudden death. The gross pathologic changes were diffuse or focal pallor of the myocardium with occasional marked pulmonary congestion. Necrotizing nonsuppurative myocarditis was consistently present. EMCV was isolated from only one of 54 feral rodents examined. No antibodies to EMCV were detected with a serum neutralization test in 79 stored sera from a wide variety of zoo mammals. Titers of 1:16, 1:16, and 1:4 were recorded for a spider monkey (Aeteles geoffroyi), a lion (Panthera leo), and an orangutan (Pongo pygmaeus), respectively. Of seven mandrills tested in 1988, six had measurable virus titers. Later testing indicated that these titers did not persist, and one mandrill with a titer > 1:128 in 1988 subsequently succumbed to EMCV infection in 1991.

  15. Seroprevalence of Toscana virus infection in Tunisia.

    Science.gov (United States)

    Fezaa, Ons; Bahri, Olfa; Alaya Bouafif, Nissaf Ben; Triki, Henda; Bouattour, Ali

    2013-12-01

    The main objective of this study was to assess the prevalence of IgG antibodies against Toscana virus (TOSV) by an ELISA test and to determine the extent of its circulation in Tunisia. An indirect ELISA test was performed to detect anti-TOSV IgG. The results were compared to those of an indirect fluorescent antibody (IFA) test. The survey tested 494 healthy people from various regions of Tunisia by ELISA for anti-TOSV IgG; 47 people (9.5%) were found to be positive. Seroprevalence varied by bioclimatic region and gender. Two hundred and twelve samples, randomly chosen from the same selected population and tested with ELISA, were retested using an IFA for IgG antibodies. An 85% concordance between the IFA and ELISA was obtained (kappa=0.650). These serological data confirm the circulation of TOSV in different bioclimatic zones in Tunisia where the vector sand flies are found. The detection of IgG against TOSV suggests that the diagnosis of TOSV infection is often neglected, as this virus often causes asymptomatic infections, with only a few patients developing severe illnesses involving neurological manifestations. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  16. Oral manifestations of hepatitis C virus infection

    Science.gov (United States)

    Carrozzo, Marco; Scally, Kara

    2014-01-01

    Extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection can affect a variety of organ systems with significant morbidity and mortality. Some of the most frequently reported EHM of HCV infection, involve the oral region predominantly or exclusively. Oral lichen planus (OLP) is a chronic inflammatory condition that is potentially malignant and represents cell-mediated reaction to a variety of extrinsic antigens, altered self-antigens, or super antigens. Robust epidemiological evidence support the link between OLP and HCV. As the virus may replicate in the oral mucosa and attract HCV-specific T lymphocytes, HCV may be implicated in OLP pathogenesis. Sjögren syndrome (SjS) is an autoimmune exocrinopathy, characterized by dryness of the mouth and eyes and a multitude of other systemic signs and symptoms. SjS patients have also an increased risk of non-Hodgkin lymphoma. Patients with chronic hepatitis C do frequently have histological signs of Sjögren-like sialadenitis with mild or even absent clinical symptoms. However, it is still unclear if HCV may cause a disease mimicking SjS or it is directly responsible for the development of SjS in a specific subset of patients. Oral squamous cell carcinoma is the most common oral malignant tumour and at least in some part of the world could be linked to HCV. PMID:24976694

  17. Hair Loss after Varicella Zoster Virus Infection

    Directory of Open Access Journals (Sweden)

    Lara El Hayderi

    2013-02-01

    Full Text Available Varicella zoster virus (VZV cutaneous infection occurs predominantly in epidermal and infundibular keratinocytes and accessorily in dermal dendritic cells. These latter cells play a role in cicatricial processes. Two patients are presented with localized alopecia after VZV infection. A 4-year-old girl presented localized hair loss affecting about 20% of her upper right eyelash immediately following the resolution of the varicella skin lesions. No regrowth was observed after 3 months. An 80-year-old woman with a prior history of localized alopecia areata of the left occipital area presented severe left herpes zoster affecting the V1 and V2 dermatomes. At precisely the same site of the previous episode, a localized plaque of alopecia areata recurred. After topical corticosteroid therapy, a progressive hair regrowth occurred after about 3 months. These case reports are the first relating cutaneous VZV infection as the origin for permanent cicatricial alopecia and transitory alopecia areata. Localized hair loss should be added to the cutaneous complications of VZV skin infection.

  18. Expression of CD154 by a Simian Immunodeficiency Virus Vector Induces Only Transitory Changes in Rhesus Macaques

    OpenAIRE

    Vida L. Hodara; Velasquillo, M. Cristina; Parodi, Laura M.; Giavedoni, Luis D.

    2005-01-01

    Human immunodeficiency virus infection is characterized by dysregulation of antigen-presenting cell function and defects in cell-mediated immunity. Recent evidence suggests that impaired ability of CD4+ T cells to upregulate the costimulatory molecule CD154 is at the core of this dysregulation. To test the hypothesis that increased expression of CD154 on infected CD4+ T cells could modulate immune function, we constructed a replication-competent simian immunodeficiency virus (SIV) vector that...

  19. Chronic Δ9-Tetrahydrocannabinol Administration May Not Attenuate Simian Immunodeficiency Virus Disease Progression in Female Rhesus Macaques

    Science.gov (United States)

    Amedee, Angela M.; Nichols, Whitney A.; LeCapitaine, Nicole J.; Stouwe, Curtis Vande; Birke, Leslie L.; Lacour, Nedra; Winsauer, Peter J.

    2014-01-01

    Abstract Persons living with HIV/AIDS (PLWHA) frequently use cannabinoids, either recreationally by smoking marijuana or therapeutically (delta-9-tetrahydrocannabinol; Δ9-THC dronabinol). Previously, we demonstrated that chronic Δ9-THC administration decreases early mortality in male simian immunodeficiency virus (SIV)-infected macaques. In this study, we sought to examine whether similar protective effects resulted from chronic cannabinoid administration in SIV-infected female rhesus macaques. Clinical and viral parameters were evaluated in eight female rhesus macaques that received either Δ9-THC (0.18–0.32 mg/kg, intramuscularly, twice daily) or vehicle (VEH) starting 28 days prior to intravenous inoculation with SIVmac251. SIV disease progression was assessed by changes in body weight, mortality, viral levels in plasma and mucosal sites, and lymphocyte subsets. In contrast to our results in male animals, chronic Δ9-THC did not protect SIV-infected female rhesus macaques from early mortality. Markers of SIV disease, including viral load and CD4+/CD8+ ratio, were not altered by Δ9-THC compared to control females; however, females that received chronic Δ9-THC did not gain as much weight as control animals. In addition, Δ9-THC administration increased total CXCR4 expression in both peripheral and duodenal CD4+ and CD8+ T lymphocytes prior to SIV inoculation. Although protection from early mortality was not evident, chronic Δ9-THC did not affect clinical markers of SIV disease progression. The contrasting effects of chronic Δ9-THC in males versus females remain to be explained, but highlight the need for further studies to explore the sex-dependent effects of Δ9-THC and other cannabinoids on the HIV disease course and their implications for virus transmission. PMID:25113915

  20. Stability of RNA silencing-based traits after virus infection

    DEFF Research Database (Denmark)

    Jørgensen, Bodil; Albrechtsen, Merete

    2007-01-01

    engineered virus resistance based on either a simple sense or an inverted repeat construct. We decided to use genetically engineered virus resistance in potato as a model system for further studies of the effect of virus infection on genetically engineered traits. We present for the first time a comparison...

  1. Transmission potential of Zika virus infection in the South Pacific

    Directory of Open Access Journals (Sweden)

    Hiroshi Nishiura

    2016-04-01

    Conclusions: The transmissibility of Zika virus infection appears to be comparable to those of dengue and chikungunya viruses. Considering that Aedes species are a shared vector, this finding indicates that Zika virus replication within the vector is perhaps comparable to dengue and chikungunya.

  2. 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.

  3. Persistent, triple-virus co-infections in mosquito cells

    Directory of Open Access Journals (Sweden)

    Malasit Prida

    2010-01-01

    Full Text Available Abstract Background It is known that insects and crustaceans can carry simultaneous, active infections of two or more viruses without showing signs of disease, but it was not clear whether co-infecting viruses occupied the same cells or different cells in common target tissues. Our previous work showed that successive challenge of mosquito cell cultures followed by serial, split-passage resulted in stabilized cultures with 100% of the cells co-infected with Dengue virus (DEN and an insect parvovirus (densovirus (DNV. By addition of Japanese encephalitis virus (JE, we tested our hypothesis that stable, persistent, triple-virus co-infections could be obtained by the same process. Results Using immunocytochemistry by confocal microscopy, we found that JE super-challenge of cells dually infected with DEN and DNV resulted in stable cultures without signs of cytopathology, and with 99% of the cells producing antigens of the 3 viruses. Location of antigens for all 3 viruses in the triple co-infections was dominant in the cell nuclei. Except for DNV, this differed from the distribution in cells persistently infected with the individual viruses or co-infected with DNV and DEN. The dependence of viral antigen distribution on single infection or co-infection status suggested that host cells underwent an adaptive process to accommodate 2 or more viruses. Conclusions Individual mosquito cells can accommodate at least 3 viruses simultaneously in an adaptive manner. The phenomenon provides an opportunity for genetic exchange between diverse viruses and it may have important medical and veterinary implications for arboviruses.

  4. Negative-strand RNA viruses: The plant-infecting counterparts

    NARCIS (Netherlands)

    Kormelink, R.J.M.; Garcia, M.L.; Goodin, M.; Sasaya, T.; Haenni, A.L.

    2011-01-01

    While a large number of negative-strand (-)RNA viruses infect animals and humans, a relative small number have plants as their primary host. Some of these have been classified within families together with animal/human infecting viruses due to similarities in particle morphology and genome

  5. Hepatitis C virus infection and risk of coronary artery disease

    DEFF Research Database (Denmark)

    Roed, Torsten; Lebech, Anne-Mette; Kjaer, Andreas

    2012-01-01

    Several chronic infections have been associated with cardiovascular diseases, including Chlamydia pneumoniae, human immunodeficiency virus and viral hepatitis. This review evaluates the literature on the association between chronic hepatitis C virus (HCV) infection and the risk of coronary artery...... disease (CAD)....

  6. Seroprevalence of hepatitis B virus infection among pregnant ...

    African Journals Online (AJOL)

    2015-06-03

    Jun 3, 2015 ... Objectives: The objectives were to determine the seroprevalence of hepatitis B virus (HBV) infection and assess the major risk factors among ... Key words: Hepatitis B surface antigen, hepatitis B virus, infectivity, Lagos, Nigeria, seroprevalence .... Z is the unit normal deviate corresponding to the desired.

  7. Phyllanthus species for chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Yun, Xia; Luo, Hui; Liu, Jian Ping

    2011-01-01

    Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists.......Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists....

  8. Herpes Simplex Virus type 2 Infection among Females in Enugu ...

    African Journals Online (AJOL)

    BACKGROUND: Herpes simplex virus type 2 infection is life long with manifestation in a small proportion of those infected. It has presented public health concern because of its progressively increasing prevalence which some authorities say is of epidemic proportion in developing countries. Herpes simplex virus type 2 has ...

  9. Co-infections with Chikungunya and Dengue Viruses, Guatemala, 2015.

    Science.gov (United States)

    Edwards, Thomas; Signor, Leticia Del Carmen Castillo; Williams, Christopher; Donis, Evelin; Cuevas, Luis E; Adams, Emily R

    2016-11-01

    We screened serum samples referred to the national reference laboratory in Guatemala that were positive for chikungunya or dengue viruses in June 2015. Co-infection with both viruses was detected by reverse transcription PCR in 46 (32%) of 144 samples. Specimens should be tested for both arboviruses to detect co-infections.

  10. Co-infections with Chikungunya and Dengue Viruses, Guatemala, 2015

    OpenAIRE

    Edwards, Thomas; Signor, Leticia del Carmen Castillo; Williams, Chris; Donis, Evelin; Cuevas, Luis; Adams, Emily

    2016-01-01

    We screened serum samples referred to the national reference laboratory in Guatemala that were positive for chikungunya or dengue viruses in June 2015. Co-infection with both viruses was detected by reverse transcription PCR in 46 (32%) of 144 samples. Specimens should be tested for both arboviruses to detect co-infections.

  11. 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 ...

  12. 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.

  13. Comparison of CIV, SIV and AIV using Decision Tree and SVM

    Directory of Open Access Journals (Sweden)

    Park Hyorin

    2016-01-01

    Full Text Available The H3N2, the canine influenza virus has numerous types of animal hosts that can live and reproduce on. They mostly settle on pigs and birds. However, some concerned voices are rising that there is high possibility that humans could be an additional victim for the canine flu. Consequently, our project group expect that the information about the H3N2’s DNA are valuable, since the information could attribute to development of vaccine and medicine. In the experiments of analysing the properties of CIV, Canine Influenza Virus with the comparison of SIV, Swine Influenza Virus and AIV, Avian Influenza Virus with the decision tree and SVM, Support Vector Machine. The result came out that CIV, SIV and AIV are alike but also different in some aspects.

  14. Bovine respiratory disease model based on dual infections with infection with bovine viral diarrhea virus and bovine corona virus

    Science.gov (United States)

    Bovine respiratory disease complex (BRDC) is the leading cause of economic loss in the U.S. cattle industry. BRDC likely results from simultaneous or sequential infections with multiple pathogens including both viruses and bacteria. Bovine viral diarrhea virus (BVDV) and bovine corona virus (BoCV...

  15. Virus-Bacteria Interactions: An Emerging Topic in Human Infection

    OpenAIRE

    Almand, Erin A.; Moore, Matthew D.; Jaykus, Lee-Ann

    2017-01-01

    Bacteria and viruses often occupy the same niches, however, interest in their potential collaboration in promoting wellness or disease states has only recently gained traction. While the interaction of some bacteria and viruses is well characterized (e.g., influenza virus), researchers are typically more interested in the location of the infection than the manner of cooperation. There are two overarching types of bacterial-virus disease causing interactions: direct interactions that in some w...

  16. Electron microscope evidence of virus infection in cultured marine fish

    Science.gov (United States)

    Sun, Xiu-Qin; Zhang, Jin-Xing; Qu, Ling-Yun

    2000-09-01

    Electron microscope investigation on the red sea bream ( Pagrosomus major), bastard halibut ( Paralichthys olivaceus) and stone flounder ( Kareius bicoloratus) in North China revealed virus infection in the bodies of the dead and diseased fish. These viruses included the lymphocystis disease virus (LDV), parvovirus, globular virus, and a kind of baculavirus which was not discovered and reported before and is now tentatively named baculavirus of stone flounder ( Kareius bicoloratus).

  17. 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.

  18. Hepatitis B virus infection in children.

    LENUS (Irish Health Repository)

    O'Gorman, C S

    2012-02-01

    Recent increases in Hepatitis B virus (HBV) infection prompted us to characterize HBV-infected children in Ireland and to audit management, by reviewing prospectively gathered data. Of 46 children (29 [63%] male), median age at presentation was 8.1 years (range 0.6-17.6), monitoring duration was 22.5 months (range 1-101), 23\\/46 (50%) were European (including 9 [19.6%] Irish), 15 (32.6%) African and 9 (19.6%) Asian. Acquisition was vertical (25\\/46 [54.3%]), horizontal (5\\/46 [10.9%]), unknown (16\\/46 [34.8%]). HBV-DNA was >100,000,000 cpm in 20\\/32 (62.5%) with chronic infection. Hepatitis B e antigen (HBeAg) was detected in 32\\/44 (72.7%). We estimate that universal neonatal vaccination (UNV-HBV) could have prevented 22% of cases, and could limit further horizontal HBV spread. This supports the recent introduction of UNV-HBV.

  19. 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.

  20. Dengue Virus Coinfection in Human Immunodeficiency Virus-1-Infected Patients on the West Coast of Mexico.

    Science.gov (United States)

    Espinoza-Gómez, Francisco; Delgado-Enciso, Iván; Valle-Reyes, Salvador; Ochoa-Jiménez, Rodolfo; Arechiga-Ramírez, Conrado; Gámez-Arroyo, José L; Vázquez-Campuzano, Roberto; Guzmán-Bracho, Carmen; Vásquez, Clemente; López-Lemus, Uriel A

    2017-09-01

    Dengue virus infection in human immunodeficiency virus (HIV)-positive patients is not well studied. Previous reports suggest a transitory inhibition of the HIV-1 viral load, as well as a benign clinical progression of dengue. The follow-up of six HIV-1-infected patients, diagnosed and hospitalized with dengue virus infection in the State of Colima, Mexico, was carried out to analyze the progression of this viral coinfection. The presence of dengue virus serotype 1 was confirmed through molecular tests. No severe complications were observed in any of the patients during dengue virus infection. Significant alteration of the HIV-1 viral loads was not observed during dengue virus infection and 6 months after coinfection. Further studies are required to understand the pathology, as well as the clinical course, of these viral coinfections.

  1. 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

  2. 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

  3. Hepatitis B virus infection in dentistry: a forgotten topic.

    Science.gov (United States)

    Mahboobi, N; Agha-Hosseini, F; Mahboobi, N; Safari, S; Lavanchy, D; Alavian, S-M

    2010-05-01

    More than two billion people have been infected with hepatitis B virus (HBV). Globally, 350-400 million suffer from chronic HBV infection. It is postulated that dentists and dental staff are infected and transmit the virus to their patients more than any other occupation. The aim of this article is to review the HBV incidence in dental society, the points of view of dentists and their patients regarding transmission of the virus during dental procedures, the occurrence of HBV outbreaks in dental clinics and the importance of methods of preventing HBV infection in dentistry.

  4. Diagnosis of Zika virus infection on a nanotechnology platform.

    Science.gov (United States)

    Zhang, Bo; Pinsky, Benjamin A; Ananta, Jeyarama S; Zhao, Su; Arulkumar, Shylaja; Wan, Hao; Sahoo, Malaya K; Abeynayake, Janaki; Waggoner, Jesse J; Hopes, Clay; Tang, Meijie; Dai, Hongjie

    2017-05-01

    We developed a multiplexed assay on a plasmonic-gold platform for measuring IgG and IgA antibodies and IgG avidity against both Zika virus (ZIKV) and dengue virus (DENV) infections. In contrast to IgM cross-reactivity, IgG and IgA antibodies against ZIKV nonstructural protein 1 (NS1) antigen were specific to ZIKV infection, and IgG avidity revealed recent ZIKV infection and past DENV-2 infection in patients in dengue-endemic regions. This assay could enable specific diagnosis of ZIKV infection over other flaviviral infections.

  5. Epidemiological and Virological Characterization of Influenza B Virus Infections.

    Directory of Open Access Journals (Sweden)

    Sivan Sharabi

    Full Text Available While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011-2014, in hospitalized and in non-hospitalized (community influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections.

  6. Estimating infectivity rates and attack windows for two viruses.

    Science.gov (United States)

    Zhang, J; Noe, D A; Wu, J; Bailer, A J; Wright, S E

    2012-12-01

    Cells exist in an environment in which they are simultaneously exposed to a number of viral challenges. In some cases, infection by one virus may preclude infection by other viruses. Under the assumption of independent times until infection by two viruses, a procedure is presented to estimate the infectivity rates along with the time window during which a cell might be susceptible to infection by multiple viruses. A test for equal infectivity rates is proposed and interval estimates of parameters are derived. Additional hypothesis tests of potential interest are also presented. The operating characteristics of these tests and the estimation procedure are explored in simulation studies. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Phenotypic changes in the brain of SIV-infected macaques exposed to methamphetamine parallel macrophage activation patterns induced by the common gamma-chain cytokine system

    Directory of Open Access Journals (Sweden)

    Nikki eBortell

    2015-09-01

    Full Text Available One factor in the development of neuroAIDS is the increase in the migration of pro-inflammatory CD8 T cells across the Blood Brain Barrier. Typically these cells are involved with keeping the viral load down. However, the persistence of above average numbers of CD8 T cells in the brain, not necessarily specific to viral peptides, is facilitated by the upregulation of IL15 from astrocytes, in the absence of IL2, in the brain environment. Both IL15 and IL2 are common gamma chain (γc cytokines. Here, using the non-human primate model of neuroAIDS, we have demonstrated that exposure to Methamphetamine, a powerful illicit drug that has been associated with HIV exposure and neuroAIDS severity, can cause an increase in molecules of the γc system. Among these molecules, IL15, which is upregulated in astrocytes by Methamphetamine, and that induces the proliferation of T cells, may also be involved in driving an inflammatory phenotype in innate immune cells of the brain. Therefore, Methamphetamine and IL15 may be critical in the development and aggravation of Central Nervous System immune-mediated inflammatory pathology in HIV-infected drug abusers.

  8. Respiratory syncytial virus: co-infection and paediatric lower respiratory tract infections.

    Science.gov (United States)

    Yoshida, Lay-Myint; Suzuki, Motoi; Nguyen, Hien Anh; Le, Minh Nhat; Dinh Vu, Thiem; Yoshino, Hiroshi; Schmidt, Wolf-Peter; Nguyen, Thi Thuy Ai; Le, Huu Tho; Morimoto, Konosuke; Moriuchi, Hiroyuki; Dang, Duc Anh; Ariyoshi, Koya

    2013-08-01

    Comprehensive population-based data on the role of respiratory viruses in the development of lower respiratory tract infections (LRTIs) remain unclear. We investigated the incidence and effect of single and multiple infections with respiratory viruses on the risk of LRTIs in Vietnam. Population-based prospective surveillance and a case-control study of hospitalised paediatric patients with acute respiratory infection (ARI) were conducted from April 2007 through to March 2010. Healthy controls were randomly recruited from the same community. Nasopharyngeal samples were collected and tested for 13 respiratory viruses using multiplex PCRs. 1992 hospitalised ARI episodes, including 397 (19.9%) with LRTIs, were enrolled. Incidence of hospitalised LRTIs among children aged respiratory syncytial virus (20.1%) and influenza A virus (12.0%) were the most common and 9.5% had multiple-viral infections. Respiratory syncytial virus and human metapneumovirus infections independently increased the risk of LRTIs. Respiratory syncytial virus further increased the risk, when co-infected with human rhinovirus, human metapneumovirus and parainfluenza virus-3 but not with influenza A virus. The case-control analysis revealed that respiratory syncytial virus and influenza A virus increased the risk of ARI hospitalisation but not human rhinovirus. Respiratory syncytial virus is the leading pathogen associated with risk of ARI hospitalisation and LRTIs in Vietnam.

  9. Western flower thrips can transmit Tomato spotted wilt virus from virus-infected tomato fruits

    Science.gov (United States)

    Acquisition and transmission of Tomato spotted wilt virus from symptomatic tomato fruits by western flower thrips was demonstrated for the first time. This suggests that infected tomato fruits may be a source of virus and also provide an additional means of virus movement between geographic areas....

  10. «I Am Legend»: comparison of the fictional virus infection and Rabies virus

    Directory of Open Access Journals (Sweden)

    José Francisco CAMACHO AGUILERA

    2016-04-01

    Full Text Available Using the movie I am legend (2007 by, the rabies virus infection is reviewed in this article, given its strong resemblance to the fictional disease created in this film caused by the virus Krippin. A review of history, virus characteristics, viral transmission, clinical manifestations, diagnostics, mortality, treatment and prevention, are presented and are contrasted with the film.

  11. West Nile virus meningitis in a patient with human immunodeficiency virus type 1 infection

    Directory of Open Access Journals (Sweden)

    D. Pilalas

    2017-09-01

    Full Text Available The emergence of West Nile virus lineage 2 in central Macedonia, Greece, in 2010 resulted in large outbreaks for 5 consecutive years. We report a case of viral meningitis in an individual infected with human immunodeficiency virus type 1, which preceded the recognition of the outbreak and was confirmed retrospectively as West Nile virus neuroinvasive disease.

  12. Unfolded protein response in hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Shiu-Wan eChan

    2014-05-01

    Full Text Available Hepatitis C virus (HCV is a single-stranded, positive-sense RNA virus of clinical importance. The virus establishes a chronic infection and can progress from chronic hepatitis, steatosis to fibrosis, cirrhosis and hepatocellular carcinoma. The mechanisms of viral persistence and pathogenesis are poorly understood. Recently the unfolded protein response (UPR, a cellular homeostatic response to endoplasmic reticulum (ER stress, has emerged to be a major contributing factor in many human diseases. It is also evident that viruses interact with the host UPR in many different ways and the outcome could be pro-viral, anti-viral or pathogenic, depending on the particular type of infection. Here we present evidence for the elicitation of chronic ER stress in HCV infection. We analyze the UPR signaling pathways involved in HCV infection, the various levels of UPR regulation by different viral proteins and finally, we propose several mechanisms by which the virus provokes the UPR.

  13. Antibody dependent enhancement of frog virus 3 infection

    Directory of Open Access Journals (Sweden)

    Penny Emily

    2010-02-01

    Full Text Available Abstract Background Viruses included in the family Iridoviridae are large, icosahedral, dsDNA viruses that are subdivided into 5 genera. Frog virus 3 (FV3 is the type species of the genus Ranavirus and the best studied iridovirus at the molecular level. Typically, antibodies directed against a virus act to neutralize the virus and limit infection. Antibody dependent enhancement occurs when viral antibodies enhance infectivity of the virus rather than neutralize it. Results Here we show that anti-FV3 serum present at the time of FV3 infection enhances infectivity of the virus in two non-immune teleost cell lines. We found that antibody dependent enhancement of FV3 was dependent on the Fc portion of anti-FV3 antibodies but not related to complement. Furthermore, the presence of anti-FV3 serum during an FV3 infection in a non-immune mammalian cell line resulted in neutralization of the virus. Our results suggest that a cell surface receptor specific to teleost cell lines is responsible for the enhancement. Conclusions This report represents the first evidence of antibody dependent enhancement in iridoviruses. The data suggests that anti-FV3 serum can either neutralize or enhance viral infection and that enhancement is related to a novel antibody dependent enhancement pathway found in teleosts that is Fc dependent.

  14. A novel single virus infection system reveals that influenza virus preferentially infects cells in g1 phase.

    Directory of Open Access Journals (Sweden)

    Ryuta Ueda

    Full Text Available BACKGROUND: Influenza virus attaches to sialic acid residues on the surface of host cells via the hemagglutinin (HA, a glycoprotein expressed on the viral envelope, and enters into the cytoplasm by receptor-mediated endocytosis. The viral genome is released and transported in to the nucleus, where transcription and replication take place. However, cellular factors affecting the influenza virus infection such as the cell cycle remain uncharacterized. METHODS/RESULTS: To resolve the influence of cell cycle on influenza virus infection, we performed a single-virus infection analysis using optical tweezers. Using this newly developed single-virus infection system, the fluorescence-labeled influenza virus was trapped on a microchip using a laser (1064 nm at 0.6 W, transported, and released onto individual H292 human lung epithelial cells. Interestingly, the influenza virus attached selectively to cells in the G1-phase. To clarify the molecular differences between cells in G1- and S/G2/M-phase, we performed several physical and chemical assays. Results indicated that: 1 the membranes of cells in G1-phase contained greater amounts of sialic acids (glycoproteins than the membranes of cells in S/G2/M-phase; 2 the membrane stiffness of cells in S/G2/M-phase is more rigid than those in G1-phase by measurement using optical tweezers; and 3 S/G2/M-phase cells contained higher content of Gb3, Gb4 and GlcCer than G1-phase cells by an assay for lipid composition. CONCLUSIONS: A novel single-virus infection system was developed to characterize the difference in influenza virus susceptibility between G1- and S/G2/M-phase cells. Differences in virus binding specificity were associated with alterations in the lipid composition, sialic acid content, and membrane stiffness. This single-virus infection system will be useful for studying the infection mechanisms of other viruses.

  15. 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.

  16. Immune regulation in chronic hepatitis C virus infection

    DEFF Research Database (Denmark)

    Hartling, Hans Jakob; Ballegaard, Vibe Cecilie; Nielsen, Nick Schou

    2016-01-01

    The immunological result of infection with Hepatitis C virus (HCV) depends on the delicate balance between a vigorous immune response that may clear the infection, but with a risk of unspecific inflammation and, or a less inflammatory response that leads to chronic infection. In general, exhaustion...... of epigenetic changes in chronic HCV infection. A vast amount of studies have revealed the complexity of immune regulation in chronic HCV infection, but the interplay between immune regulation in virus and host remains incompletely understood. This review provides an overview of regulatory functions of HCV...

  17. Reference gene selection for quantitative real-time PCR analysis in virus infected cells: SARS corona virus, Yellow fever virus, Human Herpesvirus-6, Camelpox virus and Cytomegalovirus infections

    Directory of Open Access Journals (Sweden)

    Müller Marcel A

    2005-02-01

    Full Text Available Abstract Ten potential reference genes were compared for their use in experiments investigating cellular mRNA expression of virus infected cells. Human cell lines were infected with Cytomegalovirus, Human Herpesvirus-6, Camelpox virus, SARS coronavirus or Yellow fever virus. The expression levels of these genes and the viral replication were determined by real-time PCR. Genes were ranked by the BestKeeper tool, the GeNorm tool and by criteria we reported previously. Ranking lists of the genes tested were tool dependent. However, over all, β-actin is an unsuitable as reference gene, whereas TATA-Box binding protein and peptidyl-prolyl-isomerase A are stable reference genes for expression studies in virus infected cells.

  18. Prevalence of Hepatitis B virus infection amongst parturients in the ...

    African Journals Online (AJOL)

    Background: Hepatitis B virus (HBV) infection is endemic in Nigeria and indeed the whole of Sub-Saharan Africa. The Society of Gastroenterology and Hepatology in Nigeria (SOGHIN) recommends HBV screening for all Nigerians to pave way for early detection and treatment of the infection in those who are infected and ...

  19. Influenza virus infection during pregnancy and in specific populations

    NARCIS (Netherlands)

    Meijer, WJ

    2016-01-01

    Influenza virus infection causes approximately 1 billion infections worldwide each year. These infections are usually self-limiting, but serious complications may occur, in particular in adults aged 65 years or older, patients with cardiovascular disease, asthma or autoimmune disorders and pregnant

  20. Dynamics of viral spread in bluetongue virus infected calves.

    Science.gov (United States)

    Barratt-Boyes, S M; MacLachlan, N J

    1994-06-01

    The kinetics of viremia and sites of viral replication in bluetongue virus (BTV) infected calves were characterized by virus isolation, serology and immunofluorescence staining procedures. In addition, the role of the regional lymph node and lymphatics draining inoculated skin in the pathogenesis of BTV infection was determined by analyzing efferent lymph collected from indwelling cannulas. Viremia persisted for 35 to 42 days after inoculation (DAI) and virus co-circulated with neutralizing antibodies for 23 to 26 days. Virus was first isolated from peripheral blood mononuclear (PBM) cells at 3 DAI, after stimulation of PBM cells with interleukin 2 and mitogen. BTV was frequently isolated from erythrocytes, platelets and stimulated PBM cells but never from granulocytes and rarely from plasma during viremia. Virus was consistently isolated from erythrocytes late in the course of viremia. Interruption of efferent lymph flow by cannulation delayed the onset of viremia to 7 DAI. BTV was infrequently isolated from lymph cells, and few fluorescence positive cells were observed after lymph and PBM cells were labelled with a BTV-specific monoclonal antibody. Virus was isolated from spleen by 4 DAI and most tissues by 6 DAI, whereas virus was isolated from bone marrow only at 10 DAI. Virus was not isolated from any tissue after termination of viremia. It is concluded that primary viral replication occurred in the local lymph node and BTV then was transported in low titer to secondary sites of replication via infected lymph and PBM cells. We speculate that virus replication in spleen resulted in release of virus into the circulation and non-selective infection of blood cells which disseminated BTV to other tissues. Virus association with erythrocytes likely was responsible for prolonged viremia, although infected erythrocytes eventually were cleared from the circulation and persistent BTV infection of calves did not occur.

  1. Prenatal brain MRI of fetuses with Zika virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Guillemette-Artur, Prisca [Centre Hospitalier de Polynesie Francaise, Service de Radiologie, Pirae, Tahiti (Country Unknown); Besnard, Marianne [Centre Hospitalier de Polynesie Francaise, Service de Reanimation Neo-natale, Pirae, Tahiti (Country Unknown); Eyrolle-Guignot, Dominique [Centre Hospitalier de Polynesie Francaise, Service d' Obstetrique, Pirae, Tahiti (Country Unknown); Jouannic, Jean-Marie [Universite Pierre et Marie Curie, Service de Medecine Foetale, Hopital d' Enfants Armand-Trousseau, Paris (France); Garel, Catherine [Hopital d' Enfants Armand-Trousseau, Department of Radiology, Paris (France)

    2016-06-15

    An outbreak of Zika virus was observed in French Polynesia in 2013-2014. Maternal Zika virus infection has been associated with fetal microcephaly and severe cerebral damage. To analyze the MRI cerebral findings in fetuses with intrauterine Zika virus infection. We retrospectively analyzed prospectively collected data. Inclusion criteria comprised cases with (1) estimated conception date between June 2013 and May 2014, (2) available US and MRI scans revealing severe fetal brain lesions and (3) positive polymerase chain reaction for Zika virus in the amniotic fluid. We recorded pregnancy history of Zika virus infection and analyzed US and MRI scans. Three out of 12 cases of severe cerebral lesions fulfilled all inclusion criteria. History of maternal Zika virus infection had been documented in two cases. Calcifications and ventriculomegaly were present at US in all cases. MRI showed micrencephaly (n = 3), low cerebellar biometry (n = 2), occipital subependymal pseudocysts (n = 2), polymicrogyria with laminar necrosis and opercular dysplasia (n = 3), absent (n = 1) or hypoplastic (n = 1) corpus callosum and hypoplastic brainstem (n = 1). Severe cerebral damage was observed in our series, with indirect findings suggesting that the germinal matrix is the principal target for Zika virus. The lesions are very similar to severe forms of congenital cytomegalovirus and lymphocytic choriomeningitis virus infections. (orig.)

  2. Prenatal brain MRI of fetuses with Zika virus infection.

    Science.gov (United States)

    Guillemette-Artur, Prisca; Besnard, Marianne; Eyrolle-Guignot, Dominique; Jouannic, Jean-Marie; Garel, Catherine

    2016-06-01

    An outbreak of Zika virus was observed in French Polynesia in 2013-2014. Maternal Zika virus infection has been associated with fetal microcephaly and severe cerebral damage. To analyze the MRI cerebral findings in fetuses with intrauterine Zika virus infection. We retrospectively analyzed prospectively collected data. Inclusion criteria comprised cases with (1) estimated conception date between June 2013 and May 2014, (2) available US and MRI scans revealing severe fetal brain lesions and (3) positive polymerase chain reaction for Zika virus in the amniotic fluid. We recorded pregnancy history of Zika virus infection and analyzed US and MRI scans. Three out of 12 cases of severe cerebral lesions fulfilled all inclusion criteria. History of maternal Zika virus infection had been documented in two cases. Calcifications and ventriculomegaly were present at US in all cases. MRI showed micrencephaly (n = 3), low cerebellar biometry (n = 2), occipital subependymal pseudocysts (n = 2), polymicrogyria with laminar necrosis and opercular dysplasia (n = 3), absent (n = 1) or hypoplastic (n = 1) corpus callosum and hypoplastic brainstem (n = 1). Severe cerebral damage was observed in our series, with indirect findings suggesting that the germinal matrix is the principal target for Zika virus. The lesions are very similar to severe forms of congenital cytomegalovirus and lymphocytic choriomeningitis virus infections.

  3. 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.

  4. Virus-Bacteria Interactions: An Emerging Topic in Human Infection

    Science.gov (United States)

    Almand, Erin A.; Moore, Matthew D.; Jaykus, Lee-Ann

    2017-01-01

    Bacteria and viruses often occupy the same niches, however, interest in their potential collaboration in promoting wellness or disease states has only recently gained traction. While the interaction of some bacteria and viruses is well characterized (e.g., influenza virus), researchers are typically more interested in the location of the infection than the manner of cooperation. There are two overarching types of bacterial-virus disease causing interactions: direct interactions that in some way aid the viruses, and indirect interactions aiding bacteria. The virus-promoting direct interactions occur when the virus exploits a bacterial component to facilitate penetration into the host cell. Conversely, indirect interactions result in increased bacterial pathogenesis as a consequence of viral infection. Enteric viruses mainly utilize the direct pathway, while respiratory viruses largely affect bacteria in an indirect fashion. This review focuses on some key examples of how virus-bacteria interactions impact the infection process across the two organ systems, and provides evidence supporting this as an emerging theme in infectious disease. PMID:28335562

  5. Virus-Bacteria Interactions: An Emerging Topic in Human Infection.

    Science.gov (United States)

    Almand, Erin A; Moore, Matthew D; Jaykus, Lee-Ann

    2017-03-21

    Bacteria and viruses often occupy the same niches, however, interest in their potential collaboration in promoting wellness or disease states has only recently gained traction. While the interaction of some bacteria and viruses is well characterized (e.g., influenza virus), researchers are typically more interested in the location of the infection than the manner of cooperation. There are two overarching types of bacterial-virus disease causing interactions: direct interactions that in some way aid the viruses, and indirect interactions aiding bacteria. The virus-promoting direct interactions occur when the virus exploits a bacterial component to facilitate penetration into the host cell. Conversely, indirect interactions result in increased bacterial pathogenesis as a consequence of viral infection. Enteric viruses mainly utilize the direct pathway, while respiratory viruses largely affect bacteria in an indirect fashion. This review focuses on some key examples of how virus-bacteria interactions impact the infection process across the two organ systems, and provides evidence supporting this as an emerging theme in infectious disease.

  6. Turnover rates of B cells, T cells, and NK cells in simian immunodeficiency virus-infected and uninfected rhesus macaques

    NARCIS (Netherlands)

    Boer, R.J. de; Mohri, H.; Ho, D.D.; Perelson, A.S.

    2003-01-01

    We determined average cellular turnover rates by fitting mathematical models to 5-bromo-2'-deoxyuridine measurements in SIV-infected and uninfected rhesus macaques. The daily turnover rates of CD4(+) T cells, CD4(-) T cells, CD20(+) B cells, and CD16(+) NK cells in normal uninfected rhesus macaques

  7. Feline immunodeficiency virus cross-species transmission: Implications for emergence of new lentiviral infections

    Science.gov (United States)

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

    2016-01-01

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

  8. Depletion of CD8+ cells does not affect the lifespan of productively infected cells during pathogenic sivmac239 infection of rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Shudo, Emi [Los Alamos National Laboratory; Ribeiro, Ruy M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

    2008-01-01

    While CD8+ T cell responses are clearly important in anti-viral immunity during HIV/SIV infection, the mechanisms by which CD8+ T cells induce this effect remain poorly understood, as emphasized by the failure of the Merck adenovirus-based, cytotoxic T lymphocyte (CTL)-inducing AIDS vaccine in a large phase IIb clinical trial. In this study, we measured the in vivo effect of CD8+ lymphocytes on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques by treating two groups of animals (i.e., CD8+ lymphocyte-depleted or controls) with antiretroviral therapy (PMPA and FTC). The lifespan of productively infected cells was calculated based on the slope of the decline of SIV plasma viremia using a well-accepted mathematical model. We found that, in both early (i.e., day 57 post-inoculation) and late (i.e., day 177 post-inoculation) chronic SIV infection, depletion of CD8+ lymphocytes did not result in an increased lifespan of productively infected cells in vivo. This result indicates that direct killing of cells producing virus is unlikely to be a major mechanism underlying the anti-viral effect of CD8+ T cells during SIV infection. These results have profound implications for the development of AIDS vaccines.

  9. Awareness of students graduation classes about how HPV infection viruses.

    OpenAIRE

    Jelínková, Martina

    2013-01-01

    v anglickém jazyce The thesis is dedicated to the awareness of students about the possibilities of graduation classes have HPV viruses. Introduction is devoted to the description of the theoretical and empirical chapters and a brief explanation of the issue of HPV viruses. In the beginning of the theoretical part presents brief characteristics of HPV viruses along with the history of HPV research, the incidence of disease caused due to HPV infection and disease transmission. In other chapters...

  10. Seroprevalence of Ebola virus infection in Bombali District, Sierra Leone

    Directory of Open Access Journals (Sweden)

    Nadege Goumkwa Mafopa

    2017-12-01

    Full Text Available A serosurvey of anti-Ebola Zaire virus nucleoprotein IgG prevalence was carried out among Ebola virus disease survivors and their Community Contacts in Bombali District, Sierra Leone. Our data suggest that the specie of Ebola virus (Zaire responsible of the 2013-2016 epidemic in West Africa may cause mild or asymptomatic infection in a proportion of cases, possibly due to an efficient immune response.

  11. 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...

  12. Respiratory Syncytial Virus Infection (RSV): Transmission and Prevention

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Respiratory Syncytial Virus Infection (RSV) Note: Javascript is disabled ... Infants Multimedia References & Resources Infographic Related Links Unexplained Respiratory Disease Outbreaks Red Book® Online RSV Transmission Recommend ...

  13. Schmallenberg virus infection of ruminants: challenges and opportunities for veterinarians

    Directory of Open Access Journals (Sweden)

    Claine F

    2015-06-01

    Full Text Available François Claine, Damien Coupeau, Laetitia Wiggers, Benoît Muylkens, Nathalie Kirschvink Veterinary Department, Faculty of Sciences, Namur Research Institute for Life Sciences (NARILIS, University of Namur (UNamur, Namur, Belgium Abstract: In 2011, European ruminant flocks were infected by Schmallenberg virus (SBV leading to transient disease in adult cattle but abortions and congenital deformities in calves, lambs, and goat kids. SBV belonging to the Simbu serogroup (family Bunyaviridae and genus Orthobunyavirus was first discovered in the same region where bluetongue virus serotype 8 (BTV-8 emerged 5 years before. Both viruses are transmitted by biting midges (Culicoides spp. and share several similarities. This paper describes the current knowledge of temporal and geographical spread, molecular virology, transmission and susceptible species, clinical signs, diagnosis, prevention and control, impact on ruminant health, and productivity of SBV infection in Europe, and compares SBV infection with BTV-8 infection in ruminants. Keywords: Schmallenberg virus, Europe, ruminants, review

  14. NNDSS - Table II. Cryptosporidiosis to Dengue virus infection

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue virus infection - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported...

  15. Genus Phyllanthus for chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Liu, J; Lin, Haili; McIntosh, H

    2001-01-01

    To evaluate the efficacy and safety of genus Phyllanthus for chronic hepatitis B virus (HBV) infection we performed a systematic review of randomized clinical trials. Randomized trials comparing genus Phyllanthus vs. placebo, no intervention, general nonspecific treatment, other herbal medicine...

  16. Hepatitis C virus infection of cholangiocarcinoma cell lines

    NARCIS (Netherlands)

    Fletcher, Nicola F.; Humphreys, Elizabeth; Jennings, Elliott; Osburn, William; Lissauer, Samantha; Wilson, Garrick K.; van Ijzendoorn, Sven C. D.; Baumert, Thomas F.; Balfe, Peter; Afford, Simon; McKeating, Jane A.

    Hepatitis C virus (HCV) infects the liver and hepatocytes are the major cell type supporting viral replication. Hepatocytes and cholangiocytes derive from a common hepatic progenitor cell that proliferates during inflammatory conditions, raising the possibility that cholangiocytes may support HCV

  17. Infection of Avian Pox Virus in Oriental Turtle-Doves

    Directory of Open Access Journals (Sweden)

    Kyung-Yeon Eo1, Young-Hoan Kim2, Kwang-Hyun Cho3, Jong-Sik Jang4, Tae-Hwan Kim5, Dongmi Kwak5 and Oh-Deog Kwon5*

    2011-10-01

    Full Text Available Three Oriental Turtle-doves (Streptopelia orientalis exhibiting lethargy, dyspnea, poor physical condition, and poor flight endurance, were rescued and referred to the Animal Health Center, Seoul Zoo, Korea. The doves had wart-like lesions on the legs and head. All of them died the following day after arrival, with the exception of one that survived for 6 days. Diphtheritic membranes on the tongue and oral mucosa were apparent at necropsy. Avian pox virus infection was suspected based on the proliferative skin lesions and oral diphtheritic lesions. Infection of the avian pox virus was confirmed by PCR using primers specific to the 4b core protein gene of avian pox virus. All cases were diagnosed with avian pox virus infection. This is believed to be the first description on natural infection of avian pox in Oriental Turtle-doves in Korea.

  18. Easy and Rapid Detection of Mumps Virus by Live Fluorescent Visualization of Virus-Infected Cells.

    Science.gov (United States)

    Takahashi, Tadanobu; Agarikuchi, Takashi; Kurebayashi, Yuuki; Shibahara, Nona; Suzuki, Chihiro; Kishikawa, Akiko; Fukushima, Keijo; Takano, Maiko; Suzuki, Fumie; Wada, Hirohisa; Otsubo, Tadamune; Ikeda, Kiyoshi; Minami, Akira; Suzuki, Takashi

    2015-01-01

    Mumps viruses show diverse cytopathic effects (CPEs) of infected cells and viral plaque formation (no CPE or no plaque formation in some cases) depending on the viral strain, highlighting the difficulty in mumps laboratory studies. In our previous study, a new sialidase substrate, 2-(benzothiazol-2-yl)-4-bromophenyl 5-acetamido-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosidonic acid (BTP3-Neu5Ac), was developed for visualization of sialidase activity. BTP3-Neu5Ac can easily and rapidly perform histochemical fluorescent visualization of influenza viruses and virus-infected cells without an antiviral antibody and cell fixation. In the present study, the potential utility of BTP3-Neu5Ac for rapid detection of mumps virus was demonstrated. BTP3-Neu5Ac could visualize dot-blotted mumps virus, virus-infected cells, and plaques (plaques should be called focuses due to staining of infected cells in this study), even if a CPE was not observed. Furthermore, virus cultivation was possible by direct pick-up from a fluorescent focus. In conventional methods, visible appearance of the CPE and focuses often requires more than 6 days after infection, but the new method with BTP3-Neu5Ac clearly visualized infected cells after 2 days and focuses after 4 days. The BTP3-Neu5Ac assay is a precise, easy, and rapid assay for confirmation and titration of mumps virus.

  19. Easy and Rapid Detection of Mumps Virus by Live Fluorescent Visualization of Virus-Infected Cells.

    Directory of Open Access Journals (Sweden)

    Tadanobu Takahashi

    Full Text Available Mumps viruses show diverse cytopathic effects (CPEs of infected cells and viral plaque formation (no CPE or no plaque formation in some cases depending on the viral strain, highlighting the difficulty in mumps laboratory studies. In our previous study, a new sialidase substrate, 2-(benzothiazol-2-yl-4-bromophenyl 5-acetamido-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosidonic acid (BTP3-Neu5Ac, was developed for visualization of sialidase activity. BTP3-Neu5Ac can easily and rapidly perform histochemical fluorescent visualization of influenza viruses and virus-infected cells without an antiviral antibody and cell fixation. In the present study, the potential utility of BTP3-Neu5Ac for rapid detection of mumps virus was demonstrated. BTP3-Neu5Ac could visualize dot-blotted mumps virus, virus-infected cells, and plaques (plaques should be called focuses due to staining of infected cells in this study, even if a CPE was not observed. Furthermore, virus cultivation was possible by direct pick-up from a fluorescent focus. In conventional methods, visible appearance of the CPE and focuses often requires more than 6 days after infection, but the new method with BTP3-Neu5Ac clearly visualized infected cells after 2 days and focuses after 4 days. The BTP3-Neu5Ac assay is a precise, easy, and rapid assay for confirmation and titration of mumps virus.

  20. Prevalence of viruses infecting cowpea in Uganda and their ...

    African Journals Online (AJOL)

    The main areas for cowpea cultivation in Uganda were surveyed in June and October 2006 for viruses affecting the crop. Seed and leaf samples from symptomatic and asymptomatic plants were collected from farmers' fields and analysed for infecting viruses using double antibody sandwich enzyme-linked immunosorbent ...

  1. 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 ...

  2. Proteins synthesized in tobacco mosaic virus infected protoplasts

    NARCIS (Netherlands)

    Huber, R.

    1979-01-01

    The study described here concerns the proteins, synthesized as a result of tobacco mosaic virus (TMV) multiplication in tobacco protoplasts and in cowpea protoplasts. The identification of proteins involved in the TMV infection, for instance in the virus RNA replication, helps to elucidate

  3. Viral protein synthesis in cowpea mosaic virus infected protoplasts

    NARCIS (Netherlands)

    Rottier, P.

    1980-01-01

    In contrast to the situation concerning bacterial and, to a lesser extent, animal RNA viruses, little is known about the biochemical processes occurring in plant cells due to plant RNA virus infection. Such processes are difficult to study using intact plants or leaves. Great effort has

  4. 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.

  5. Viral microRNAs targeting virus genes promote virus infection in shrimp in vivo.

    Science.gov (United States)

    He, Yaodong; Yang, Kai; Zhang, Xiaobo

    2014-01-01

    Viral microRNAs (miRNAs), most of which are characterized in cell lines, have been found to play important roles in the virus life cycle to avoid attack by the host immune system or to keep virus in the latency state. Viral miRNAs targeting virus genes can inhibit virus infection. In this study, in vivo findings in Marsupenaeus japonicus shrimp revealed that the viral miRNAs could target virus genes and further promote the virus infection. The results showed that white spot syndrome virus (WSSV)-encoded miRNAs WSSV-miR-66 and WSSV-miR-68 were transcribed at the early stage of WSSV infection. When the expression of WSSV-miR-66 and WSSV-miR-68 was silenced with sequence-specific anti-miRNA oligonucleotides (AMOs), the number of copies of WSSV and the WSSV-infected shrimp mortality were significantly decreased, indicating that the two viral miRNAs had a great effect on virus infection. It was revealed that the WSSV wsv094 and wsv177 genes were the targets of WSSV-miR-66 and that the wsv248 and wsv309 genes were the targets of WSSV-miR-68. The data demonstrate that the four target genes play negative roles in the WSSV infection. The targeting of the four virus genes by WSSV-miR-66 and WSSV-miR-68 led to the promotion of virus infection. Therefore, our in vivo findings show a novel aspect of viral miRNAs in virus-host interactions.

  6. Background review for diagnostic test development for Zika virus infection.

    Science.gov (United States)

    Charrel, Rémi N; Leparc-Goffart, Isabelle; Pas, Suzan; de Lamballerie, Xavier; Koopmans, Marion; Reusken, Chantal

    2016-08-01

    To review the state of knowledge about diagnostic testing for Zika virus infection and identify areas of research needed to address the current gaps in knowledge. We made a non-systematic review of the published literature about Zika virus and supplemented this with information from commercial diagnostic test kits and personal communications with researchers in European preparedness networks. The review covered current knowledge about the geographical spread, pathogen characteristics, life cycle and infection kinetics of the virus. The available molecular and serological tests and biosafety issues are described and discussed in the context of the current outbreak strain. We identified the following areas of research to address current knowledge gaps: (i) an urgent assessment of the laboratory capacity and capability of countries to detect Zika virus; (ii) rapid and extensive field validation of the available molecular and serological tests in areas with and without Zika virus transmission, with a focus on pregnant women; (iii) monitoring the genomic diversity of circulating Zika virus strains; (iv) prospective studies into the virus infection kinetics, focusing on diagnostic sampling (specimen types, combinations and timings); and (v) developing external quality assessments for molecular and serological testing, including differential diagnosis for similar viruses and symptom clusters. The availability of reagents for diagnostic development (virus strains and antigens, quantified viral ribonucleic acid) needs to be facilitated. An international laboratory response is needed, including preparation of protocols for prospective studies to address the most pressing information needs.

  7. Mitigating Prenatal Zika Virus Infection in the Americas.

    Science.gov (United States)

    Ndeffo-Mbah, Martial L; Parpia, Alyssa S; Galvani, Alison P

    2016-10-18

    Because of the risk for Zika virus infection in the Americas and the links between infection and microcephaly, other serious neurologic conditions, and fetal death, health ministries across the region have advised women to delay pregnancy. However, the effectiveness of this policy in reducing prenatal Zika virus infection has yet to be quantified. To evaluate the effectiveness of pregnancy-delay policies on the incidence and prevalence of prenatal Zika virus infection. Vector-borne Zika virus transmission model fitted to epidemiologic data from 2015 to 2016 on Zika virus infection in Colombia. Colombia, August 2015 to July 2017. Population of Colombia, stratified by sex, age, and pregnancy status. Recommendations to delay pregnancy by 3, 6, 9, 12, or 24 months, at different levels of adherence. Weekly and cumulative incidence of prenatal infections and microcephaly cases. With 50% adherence to recommendations to delay pregnancy by 9 to 24 months, the cumulative incidence of prenatal Zika virus infections is likely to decrease by 17% to 44%, whereas recommendations to delay pregnancy by 6 or fewer months are likely to increase prenatal infections by 2% to 7%. This paradoxical exacerbation of prenatal Zika virus exposure is due to an elevated risk for pregnancies to shift toward the peak of the outbreak. Sexual transmission was not explicitly accounted for in the model because of limited data but was implicitly subsumed within the overall transmission rate, which was calibrated to observed incidence. Pregnancy delays can have a substantial effect on reducing cases of microcephaly but risks exacerbating the Zika virus outbreak if the duration is not sufficient. Duration of the delay, population adherence, and the timing of initiation of the intervention must be carefully considered. National Institutes of Health.

  8. Seroprevalence and Correlates of Hepatitis C Virus Infection in ...

    African Journals Online (AJOL)

    Hepatitis C virus (HCV) is a hepatotropic virus and the cause of the majority of the cases of the formerly called. “transfusion – related non-A, non-B hepatitis” with profound effect in the liver.[1,2] HCV infection is one of the leading public health challenges globally accounting for about 115 million infections; 11 million of whom ...

  9. Varicella-zoster virus infections – antiviral therapy and diagnosis

    Directory of Open Access Journals (Sweden)

    Sauerbrei, Andreas

    2016-02-01

    Full Text Available Varicella-zoster virus is an important human pathogen that causes varicella after primary infection and zoster after recurrence. Following primary infection, the virus remains latently for life in dorsal root and cranial nerve ganglia. Varicella and zoster are worldwide widespread diseases and may be associated with significant complications. This manuscript presents a short overview about the fundamental knowledge including the most important clinical signs, the capabilities for antiviral treatment and the spectrum of methods for laboratory diagnosis.

  10. Hepatitis A virus infection: Epidemiology and genetic diversity

    OpenAIRE

    Báez Triana, Paula Andrea; Navas Navas, María Cristina

    2015-01-01

    Hepatitis A virus infection is a global public health problem. The virus has a wide range of distribution and it is the main cause of acute hepatitis transmitted by the enteric route in Latin America. The viral particle is stable under environmental conditions and conserves its infectivity for several weeks, enabling its transmission by contaminated water and food. Worldwide, different epidemiological patterns have been identified, which may change over time by modification of social and e...

  11. Hepatitis delta virus infection: open issues.

    Science.gov (United States)

    Niro, Grazia Anna; Gioffreda, Domenica; Fontana, Rosanna

    2011-01-01

    Hepatitis delta virus (HDV) consists of a circular single-stranded RNA genome which assembles two viral proteins and acquires a lipid envelope in which the hepatitis B surface antigens (HBsAg) are embedded. HDV does not encode its own polymerase, but exploits a cellular enzyme for its replication. A better understanding of the mechanisms of HDV replication mechanism would provide new insights for antiviral strategies. Based on genomic variability, eight major genotypes of HDV have been identified, which differ as much as 40% in the nucleotide sequence. The cloning of HDV-RNA has provided genetic probes for the measurement of HDV-RNA in serum and liver; the sensitivity of HDV-RNA detection improved significantly when the reverse transcriptase-polymerase chain reaction (PCR) technique was introduced. As no commercial test is standardized for viral load detection, home-made assays have been developed in the different referral centers, which may not be comparable. Quantification of HDV in serum by real-time PCR has been recently proposed in the management of chronically infected patients. No specific inhibitors of HDV are available at present and, in spite of the crucial relationship between HDV and HBV, drugs that block HBV have only a theoretical but no sound effect on HDV replication. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

  12. [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.

  13. Inhalational Monkeypox Virus Infection in Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Roy eBarnewall

    2012-09-01

    Full Text Available An inhalation exposure system was characterized to deliver aerosolized monkeypox virus (MPXV, and a nonhuman primate (NHP inhalation monkeypox model was developed in cynomologus macaques. A head-only aerosol exposure system was characterized, and two sampling methods were evaluated: liquid impingement via an impinger and impaction via a gelatin filter. The aerosol concentrations obtained with the gelatin filter and impinger were virtually identical, indicating that either method is acceptable for sampling aerosols containing MPXV. The mass median aerodynamic diameter (MMAD was for individual aerosol tests in the aerosol system characterization and the NHP study ranged from 1.08 to 1.15 µm, indicating that the aerosol particles were of a sufficient size to reach the alveoli. Six cynomolgus macaques (four male and two female were used on study. The animals were aerosol exposed with MPXV and received doses between 2.51 x 104 to 9.28 x 105 plaque forming units (pfu inhaled. Four of the six animals died or were euthanized due to their moribund conditions. Both animals that received the lowest exposure doses survived to the end of the observation period. The inhalation LD50 was determined to be approximately 7.8 x 104 pfu inhaled. These data demonstrate that an inhalation MPXV infection model has been developed in the cynomolgus macaque with disease course and lethal dose similar to previously published data.

  14. Cognitive dysfunction and hepatitis C virus infection.

    Science.gov (United States)

    Solinas, Antonio; Piras, Maria Rita; Deplano, Angelo

    2015-05-08

    Cognitive dysfunction in patients with chronic hepatitis C virus (HCV) infection is a distinct form of minimal hepatic encephalopathy (MHE). In fact, the majority of HCV-positive patients, irrespective of the grading of liver fibrosis, display alterations of verbal learning, attention, executive function, and memory when they are evaluated by suitable neuropsychological tests. Similarities between the cognitive dysfunction of HCV patients and MHE of patients with different etiologies are unclear. It is also unknown how the metabolic alterations of advanced liver diseases interact with the HCV-induced cognitive dysfunction, and whether these alterations are reversed by antiviral therapies. HCV replication in the brain may play a role in the pathogenesis of neuroinflammation. HCV-related brain dysfunction may be associated with white matter neuronal loss, alterations of association tracts and perfusion. It is unclear to what extent, in patients with cirrhosis, HCV triggers an irreversible neurodegenerative brain damage. New insights on this issue will be provided by longitudinal studies using the protocols established by the diagnostic and statistical manual of mental disorders fifth edition for cognitive disorders. The domains to be evaluated are complex attention; executive functions; learning and memory; perceptual motor functions; social cognition. These evaluations should be associated with fluorodeoxyglucose positron emission tomography and magnetic resonance imaging (MRI) protocols for major cognitive disorders including magnetic resonance spectroscopy, diffusion tensor imaging, magnetic resonance perfusion, and functional MRI. Also, the characteristics of portal hypertension, including the extent of liver blood flow and the type of portal shunts, should be evaluated.

  15. Prevention and management of neonatal herpes simplex virus infections

    OpenAIRE

    Allen, Upton D; Robinson, Joan L

    2014-01-01

    Human herpes simplex virus (HSV) infection in neonates can result in devastating outcomes, including mortality and significant morbidity. All infants are potentially at risk for neonatal HSV infection. This position statement reviews epidemiology, transmission and risk factors, with a focus on intrapartum infection. It considers diagnosis and prognosis according to infection category, along with testing modalities and limitations. Recommendations for managing newborns known to have been expos...

  16. 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...

  17. MG-132 reduces virus release in Bovine herpesvirus-1 infection

    OpenAIRE

    Fiorito, Filomena; Iovane, Valentina; Cantiello, Antonietta; Marullo, Annarosaria; Martino, Luisa De; Iovane, Giuseppe

    2017-01-01

    Bovine herpesvirus 1 (BoHV-1) can provoke conjunctivitis, abortions and shipping fever. BoHV-1 infection can also cause immunosuppression and increased susceptibility to secondary bacterial infections, leading to pneumonia and occasionally to death. Herein, we investigated the influence of MG-132, a proteasome inhibitor, on BoHV-1 infection in bovine kidney (MDBK) cells. Infection of MDBK cells with BoHV-1 induces apoptotic cell death that enhances virus release. Whereas, MG-132 inhibited vir...

  18. Aichi virus infection in children with acute gastroenteritis in Finland.

    Science.gov (United States)

    Kaikkonen, S; Räsänen, S; Rämet, M; Vesikari, T

    2010-08-01

    Aichi virus has been proposed as a novel causative agent of acute gastroenteritis. In addition to several Asian countries, South America and Africa, Aichi virus has also recently been found in Europe. Our objective was to study the causative role of Aichi virus in children with acute gastroenteritis in Finland. We analysed 595 stool specimens from infants in an efficacy trial of rotavirus vaccine and 468 stool specimens from children in a hospital-based epidemiological and aetiological study of acute gastroenteritis. The screening was done by nested reverse transcription-polymerase chain reaction amplifying a 519-bp segment and a 223-bp segment in the 3CD junction region of non-structural proteins. Aichi virus was detected in five stool samples (0.5%), of which four were co-infections with other gastroenteritis viruses. Two Aichi virus genotypes, A and B, were found. Aichi virus appears to be rare in children with acute gastroenteritis in Finland.

  19. Infectious salmon anaemia virus (ISAV) mucosal infection in Atlantic salmon.

    Science.gov (United States)

    Aamelfot, Maria; McBeath, Alastair; Christiansen, Debes H; Matejusova, Iveta; Falk, Knut

    2015-10-21

    All viruses infecting fish must cross the surface mucosal barrier to successfully enter a host. Infectious salmon anaemia virus (ISAV), the causative agent of the economically important infectious salmon anaemia (ISA) in Atlantic salmon, Salmo salar L., has been shown to use the gills as its entry point. However, other entry ports have not been investigated despite the expression of virus receptors on the surface of epithelial cells in the skin, the gastrointestinal (GI) tract and the conjunctiva. Here we investigate the ISAV mucosal infection in Atlantic salmon after experimental immersion (bath) challenge and in farmed fish collected from a confirmed outbreak of ISA in Norway. We show for the first time evidence of early replication in several mucosal surfaces in addition to the gills, including the pectoral fin, skin and GI tract suggesting several potential entry points for the virus. Initially, the infection is localized and primarily infecting epithelial cells, however at later stages it becomes systemic, infecting the endothelial cells lining the circulatory system. Viruses of low and high virulence used in the challenge revealed possible variation in virus progression during infection at the mucosal surfaces.

  20. The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-dimethylsuccinyl}-betulinic acid

    Directory of Open Access Journals (Sweden)

    Aiken Christopher

    2004-06-01

    Full Text Available Abstract Background Despite the effectiveness of currently available antiretroviral therapies in the treatment of HIV-1 infection, a continuing need exists for novel compounds that can be used in combination with existing drugs to slow the emergence of drug-resistant viruses. We previously reported that the small molecule 3-O-{3',3'-dimethylsuccinyl}-betulinic acid (DSB specifically inhibits HIV-1 replication by delaying the processing of the CA-SP1 junction in Pr55Gag. By contrast, SIVmac239 replicates efficiently in the presence of high concentrations of DSB. To determine whether sequence differences in the CA-SP1 junction can fully account for the differential sensitivity of HIV-1 and SIV to DSB, we engineered mutations in this region of two viruses and tested their sensitivity to DSB in replication assays using activated human primary CD4+ T cells. Results Substitution of the P2 and P1 residues of HIV-1 by the corresponding amino acids of SIV resulted in strong resistance to DSB, but the mutant virus replicated with reduced efficiency. Conversely, replication of an SIV mutant containing three amino acid substitutions in the CA-SP1 cleavage site was highly sensitive to DSB, and the mutations resulted in delayed cleavage of the CA-SP1 junction in the presence of the drug. Conclusions These results demonstrate that the CA-SP1 junction in Pr55Gag represents the primary viral target of DSB. They further suggest that the therapeutic application of DSB will be accompanied by emergence of mutant viruses that are highly resistant to the drug but which exhibit reduced fitness relative to wild type HIV-1.

  1. Infection of Mosquito Cells (C6/36) by Dengue-2 Virus Interferes with Subsequent Infection by Yellow Fever Virus.

    Science.gov (United States)

    Abrao, Emiliana Pereira; da Fonseca, Benedito Antônio Lopes

    2016-02-01

    Dengue is one of the most important diseases caused by arboviruses in the world. Yellow fever is another arthropod-borne disease of great importance to public health that is endemic to tropical regions of Africa and the Americas. Both yellow fever and dengue viruses are flaviviruses transmitted by Aedes aegypti mosquitoes, and then, it is reasonable to consider that in a given moment, mosquito cells could be coinfected by both viruses. Therefore, we decided to evaluate if sequential infections of dengue and yellow fever viruses (and vice-versa) in mosquito cells could affect the virus replication patterns. Using immunofluorescence and real-time PCR-based replication assays in Aedes albopictus C6/36 cells with single or sequential infections with both viruses, we demonstrated the occurrence of viral interference, also called superinfection exclusion, between these two viruses. Our results show that this interference pattern is particularly evident when cells were first infected with dengue virus and subsequently with yellow fever virus (YFV). Reduction in dengue virus replication, although to a lower extent, was also observed when C6/36 cells were initially infected with YFV followed by dengue virus infection. Although the importance that these findings have on nature is unknown, this study provides evidence, at the cellular level, of the occurrence of replication interference between dengue and yellow fever viruses and raises the question if superinfection exclusion could be a possible explanation, at least partially, for the reported lack of urban yellow fever occurrence in regions where a high level of dengue transmission occurs.

  2. Neutralizing Antibodies after Infection with Dengue 1 Virus

    Science.gov (United States)

    Alvarez, Mayling; Rodriguez-Roche, Rosmari; Bernardo, Lídice; Montes, Tibaire; Vazquez, Susana; Morier, Luis; Alvarez, Angel; Gould, Ernest A; Halstead, Scott B

    2007-01-01

    Severity of disease is markedly increased when infection with dengue virus type 2 (DENV-2) follows infection with DENV-1. Studies have shown that heterologous neutralizing antibody titers are inversely correlated with severity of a second infection. If this mechanism controlled disease severity in Cuba, heterotypic antibody titers should have declined over time. To determine whether phenotypic changes in dengue antibodies occur over time, we analyzed serum samples collected 4–8 and 20–22 years after DENV-1 infection. We found a significant increase in mean titer of homologous DENV-1 neutralizing antibodies and a significant decrease in heterologous antibodies to 1 of 2 genotypes of DENV-2 virus (the American genotype). Asian DENV-2 viruses were not neutralized during either interval; however, the American genotype underwent phenotypic changes in heterotypic viral neutralizing antibodies in the predicted direction. This finding may be related to the time-dependent changes in severity of disease found with secondary dengue infection. PMID:17479892

  3. Canine distemper virus infection in a lesser grison (Galictis cuja: first report and virus phylogeny

    Directory of Open Access Journals (Sweden)

    Jane Megid

    2013-02-01

    Full Text Available Infectious diseases in wild animals have been increasing as a result of their habitat alterations and closer contact with domestic animals. Canine distemper virus (CDV has been reported in several species of wild carnivores, presenting a threat to wildlife conservation. We described the first case of canine distemper virus infection in lesser grison (Galictis cuja. A free-ranging individual, with no visible clinical sigs, presented sudden death after one day in captivity. Molecular diagnosis for CDV infection was performed using whole blood collected by postmortem intracardiac puncture, which resulted positive. The virus phylogeny indicated that domestic dogs were the probable source of infection.

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

    Directory of Open Access Journals (Sweden)

    José L. Affranchino

    2014-01-01

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

  5. Epidemiology and neurological complications of infection by the Zika virus: a new emerging neurotropic virus.

    Science.gov (United States)

    Carod-Artal, Francisco J

    2016-04-01

    The current epidemic outbreak due to Zika virus began in 2015 and since then it has been reported in 31 countries and territories in America. The epidemiological and clinical aspects related to infection by Zika virus are reviewed. Since 2007, 55 countries in America, Asia, Africa and Oceania have detected local transmission of the virus. This epidemic has affected almost 1.5 million people in Brazil. 80% of the cases are asymptomatic. The symptoms of Zika virus disease include fever, maculopapular rash, arthralgia and non-purulent conjunctivitis. The symptoms are usually self-limiting and last one week. An increase in the incidence of cases of microcephaly, retinal lesions and Guillain-Barre syndrome associated with the Zika virus has been reported. Zika-associated Guillain-Barre syndrome in Polynesia is a pure motor axonal variant. The RNA of the Zika virus has been identified in samples of brain tissue, placenta and amniotic liquid of children with microcephaly and in the still-born infants of women infected by Zika during pregnancy. The reverse transcription polymerase chain reaction test is recommended to detect viral RNA, and serological tests (IgM ELISA and neutralising antibodies) should be conducted to confirm infection by Zika. The differential diagnosis includes infection by the dengue and chikungunya viruses. Knowledge about the pathogenic mechanisms involved in infection due to Zika virus and its long-term consequences in adults and newborn infants is still limited.

  6. Effects of acute respiratory virus infection upon tracheal mucous transport

    Energy Technology Data Exchange (ETDEWEB)

    Gerrard, C.S.; Levandowski, R.A.; Gerrity, T.R.; Yeates, D.B.; Klein, E.

    Tracheal mucous velocity was measured in 13 healthy non-smokers using an aerosol labelled with /sup 99m/Tc and a multidetector probe during respiratory virus infections. The movement of boluses of tracheal mucous were either absent or reduced in number in five subjects with myxovirus infection (four influenza and one respiratory syncytial virus) within 48 hr of the onset of symptoms and in four subjects 1 wk later. One subject with influenza still had reduced bolus formation 12-16 wk after infection. Frequent coughing was a feature of those subjects with absent tracheal boluses. In contrast, four subjects with rhinovirus infection had normal tracheal mucous velocity at 48 hr after the onset of symptoms (4.1 +/- 1.3 mm/min). Tracheal mucous velocity was also normal (4.6 +/- 1.1 mm/min) in four subjects in whom no specific viral agent could be defined but had typical symptomatology of respiratory viral infection. During health tracheal mucous velocity was normal (4.8 +/- 1.6 mm/min) in the eleven subjects who had measurements made. Disturbances in tracheal mucous transport during virus infection appear to depend upon the type of virus and are most severe in influenza A and respiratory syncytial virus infection.

  7. Varicella-zoster virus (chickenpox) infection in pregnancy

    DEFF Research Database (Denmark)

    Lamont, Ronald F; Sobel, Jack D; Carrington, D

    2011-01-01

    Please cite this paper as: Lamont R, Sobel J, Carrington D, Mazaki-Tovi S, Kusanovic J, Vaisbuch E, Romero R. Varicella-zoster virus (chickenpox) infection in pregnancy. BJOG 2011; DOI: 10.1111/j.1471-0528.2011.02983.x. Congenital varicella syndrome, maternal varicella-zoster virus pneumonia...... and neonatal varicella infection are associated with serious fetomaternal morbidity and, not infrequently, mortality. Vaccination against varicella-zoster virus can prevent the disease, and outbreak control limits the exposure of pregnant women to the infectious agent. Maternal varicella-zoster immunoglobulin...

  8. Chronic West Nile virus infection in kea (Nestor notabilis).

    Science.gov (United States)

    Bakonyi, Tamás; Gajdon, Gyula K; Schwing, Raoul; Vogl, Wolfgang; Häbich, Annett-Carolin; Thaller, Denise; Weissenböck, Herbert; Rudolf, Ivo; Hubálek, Zdenek; Nowotny, Norbert

    2016-02-01

    Six kea (Nestor notabilis) in human care, naturally infected with West Nile virus (WNV) lineage 2 in Vienna, Austria, in 2008, developed mild to fatal neurological signs. WNV RNA persisted and the virus evolved in the birds' brains, as demonstrated by (phylo)genetic analyses of the complete viral genomes detected in kea euthanized between 2009 and 2014. WNV antibodies persisted in the birds, too. Chronic WNV infection in the brain might contribute to the circulation of the virus through oral transmission to predatory birds. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. The Aedes aegypti toll pathway controls dengue virus infection.

    Directory of Open Access Journals (Sweden)

    Zhiyong Xi

    2008-07-01

    Full Text Available Aedes aegypti, the mosquito vector of dengue viruses, utilizes its innate immune system to ward off a variety of pathogens, some of which can cause disease in humans. To date, the features of insects' innate immune defenses against viruses have mainly been studied in the fruit fly Drosophila melanogaster, which appears to utilize different immune pathways against different types of viruses, in addition to an RNA interference-based defense system. We have used the recently released whole-genome sequence of the Ae. aegypti mosquito, in combination with high-throughput gene expression and RNA interference (RNAi-based reverse genetic analyses, to characterize its response to dengue virus infection in different body compartments. We have further addressed the impact of the mosquito's endogenous microbial flora on virus infection. Our findings indicate a significant role for the Toll pathway in regulating resistance to dengue virus, as indicated by an infection-responsive regulation and functional assessment of several Toll pathway-associated genes. We have also shown that the mosquito's natural microbiota play a role in modulating the dengue virus infection, possibly through basal-level stimulation of the Toll immune pathway.

  10. Embryo transfer from cattle infected with bluetongue virus.

    Science.gov (United States)

    Bowen, R A; Howard, T H; Elsden, R P; Seidel, G E

    1983-09-01

    Embryos recovered nonsurgically from donor cattle during the peak of bluetongue viremia were surgically transferred to seronegative recipients 7 to 8 or 10 to 11 days after the onset of donor estrus. Virus was isolated from the uterine flushing medium recovered from 11 of the 20 donors. Bluetongue virus was not isolated from the blood of any of 39 recipients, nor did any recipient seroconvert to the virus following transfer. The number of recipients that became pregnant after transfer of embryos from infected donors (21 of 39) was not significantly different from contemporary controls. Virus antigen was not detected by immunofluorescence in any of 63 embryos and oocytes recovered from viremic donors. These results indicate that under standard embryo transfer conditions, transmission of bluetongue virus from infected donors to uninfected recipients is unlikely to occur.

  11. Common variable immunodeficiency following Epstein-Barr virus infection.

    Science.gov (United States)

    Zuccaro, G; Della Bella, S; Polizzi, B; Vanoli, M; Scorza, R

    1997-01-01

    The authors present a case of a patient who developed recurrent bacterial upper respiratory and pulmonary infections and marked hypogammaglobulinemia with a gradual decrease of serum IgG, IgA and IgM some months after acute Epstein-Barr virus infection. Test for identification of lymphocyte subpopulation showed increased CD8+ T-cells with a surface phenotype (CD8+, CD57+, HLA-DR+) characteristic of virus-induced, activated cytotoxic cells. Viral investigations showed a positive anti-EBNA titer, an IgG titer anti-VCA of 1:40, a negative IgG titer anti-EA and human immunodeficiency virus negativity. The authors conclude that these clinical features are indicative of possible common variable immunodeficiency following Epstein-Barr virus infection.

  12. Clinical and laboratory diagnosis of influenza virus infections.

    Science.gov (United States)

    Newton, D W; Treanor, J J; Menegus, M A

    2000-03-01

    Influenza epidemics account for more than 20,000 deaths in the United States each year, as well as substantial morbidity, medical costs, and time away from work and school. Since the 1950s, the principal weapon against these seasonal epidemics has been killed virus vaccine formulations. Despite massive efforts to immunize at-risk individuals against influenza, not everyone receives the vaccine. In addition, use of some drugs, such as amantadine and rimantadine, can lead to the development of drug resistant viruses in infected individuals and to transmission of these viruses to susceptible individuals. The many factors that contribute to the high annual incidence of influenza virus infections mandate prompt clinical recognition and appropriate patient management. Rapid diagnostic tests have been developed that may make it possible to avoid the use of antibacterial drugs, quickly decide whether isolation of infected patients is needed, and discharge hospitalized patients sooner.

  13. Natural simian immunodeficiency virus transmission in mandrills: a family affair?

    Science.gov (United States)

    Fouchet, David; Verrier, Delphine; Ngoubangoye, Barthélémy; Souquière, Sandrine; Makuwa, Maria; Kazanji, Mirdad; Gonzalez, Jean-Paul; Pontier, Dominique

    2012-09-07

    Understanding how pathogens spread and persist in the ecosystem is critical for deciphering the epidemiology of diseases of significance for global health and the fundamental mechanisms involved in the evolution of virulence and host resistance. Combining long-term behavioural and epidemiological data collected in a naturally infected mandrill population and a Bayesian framework, the present study investigated unknown aspects of the eco-epidemiology of simian immunodeficiency virus (SIV), the recent ancestor of HIV. Results show that, in contrast to what is expected from aggressive and sexual transmission (i.e. the two commonly accepted transmission modes for SIV), cases of SIVmnd-1 subtype were significantly correlated among related individuals (greater than 30% of the observed cases). Challenging the traditional view of SIV, this finding suggests the inheritance of genetic determinants of susceptibility to SIV and/or a role for behavioural interactions among maternal kin affecting the transmission of the virus, which would highlight the underappreciated role of sociality in the spread of infectious diseases. Outcomes of this study also provide novel insights into the role of host social structure in the evolution of pathogens.

  14. Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Christine M Fennessey

    2017-05-01

    Full Text Available HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total viral load value represents the sum of many individual infection events, which are difficult to independently track using conventional sequencing approaches. To overcome this challenge, we generated a genetically tagged virus stock (SIVmac239M with a 34-base genetic barcode inserted between the vpx and vpr accessory genes of the infectious molecular clone SIVmac239. Next-generation sequencing of the virus stock identified at least 9,336 individual barcodes, or clonotypes, with an average genetic distance of 7 bases between any two barcodes. In vitro infection of rhesus CD4+ T cells and in vivo infection of rhesus macaques revealed levels of viral replication of SIVmac239M comparable to parental SIVmac239. After intravenous inoculation of 2.2x105 infectious units of SIVmac239M, an average of 1,247 barcodes were identified during acute infection in 26 infected rhesus macaques. Of the barcodes identified in the stock, at least 85.6% actively replicated in at least one animal, and on average each barcode was found in 5 monkeys. Four infected animals were treated with combination antiretroviral therapy (cART for 82 days starting on day 6 post-infection (study 1. Plasma viremia was reduced from >106 to <15 vRNA copies/mL by the time treatment was interrupted. Virus rapidly rebounded following treatment interruption and between 87 and 136 distinct clonotypes were detected in plasma at peak rebound viremia. This study confirmed that SIVmac239M viremia could be successfully curtailed with cART, and that upon cART discontinuation, rebounding viral variants could be identified and quantified. An additional 6 animals infected with SIVmac239M were treated with cART beginning on day 4 post-infection for 305, 374, or 482 days (study 2. Upon treatment interruption, between 4 and 8 distinct viral clonotypes were detected in each animal at peak rebound

  15. Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy

    Science.gov (United States)

    Pinkevych, Mykola; Reynaldi, Arnold; Reid, Carolyn; Newman, Laura; Lipkey, Leslie; Bosche, William J.; Ott, David E.; Estes, Jacob D.; Del Prete, Gregory Q.; Lifson, Jeffrey D.; Davenport, Miles P.; Keele, Brandon F.

    2017-01-01

    HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total viral load value represents the sum of many individual infection events, which are difficult to independently track using conventional sequencing approaches. To overcome this challenge, we generated a genetically tagged virus stock (SIVmac239M) with a 34-base genetic barcode inserted between the vpx and vpr accessory genes of the infectious molecular clone SIVmac239. Next-generation sequencing of the virus stock identified at least 9,336 individual barcodes, or clonotypes, with an average genetic distance of 7 bases between any two barcodes. In vitro infection of rhesus CD4+ T cells and in vivo infection of rhesus macaques revealed levels of viral replication of SIVmac239M comparable to parental SIVmac239. After intravenous inoculation of 2.2x105 infectious units of SIVmac239M, an average of 1,247 barcodes were identified during acute infection in 26 infected rhesus macaques. Of the barcodes identified in the stock, at least 85.6% actively replicated in at least one animal, and on average each barcode was found in 5 monkeys. Four infected animals were treated with combination antiretroviral therapy (cART) for 82 days starting on day 6 post-infection (study 1). Plasma viremia was reduced from >106 to <15 vRNA copies/mL by the time treatment was interrupted. Virus rapidly rebounded following treatment interruption and between 87 and 136 distinct clonotypes were detected in plasma at peak rebound viremia. This study confirmed that SIVmac239M viremia could be successfully curtailed with cART, and that upon cART discontinuation, rebounding viral variants could be identified and quantified. An additional 6 animals infected with SIVmac239M were treated with cART beginning on day 4 post-infection for 305, 374, or 482 days (study 2). Upon treatment interruption, between 4 and 8 distinct viral clonotypes were detected in each animal at peak rebound viremia. The

  16. Neuromuscular Manifestations of West Nile Virus Infection

    Directory of Open Access Journals (Sweden)

    A. Arturo eLeis

    2012-03-01

    Full Text Available The most common neuromuscular manifestation of West Nile virus (WNV infection is a poliomyelitis syndrome with asymmetric paralysis variably involving one (monoparesis to four limbs (quadriparesis, with or without brainstem involvement and respiratory failure. This syndrome of acute flaccid paralysis may occur without overt fever or meningoencephalitis. Although involvement of anterior horn cells in the spinal cord and motor neurons in the brainstem are the major sites of pathology responsible for neuromuscular signs, inflammation also may involve skeletal or cardiac muscle (myositis, myocarditis, motor axons (polyradiculitis, peripheral nerve (Guillain-Barré syndrome, brachial plexopathy. In addition, involvement of spinal sympathetic neurons and ganglia provides a plausible explanation for autonomic instability seen in some patients. Many patients also experience prolonged subjective generalized weakness and disabling fatigue. Despite recent evidence that WNV may persist long term in the central nervous system or periphery in animals, the evidence in humans is controversial. WNV persistence would be of great concern in immunosuppressed patients or in those with prolonged or recurrent symptoms. Support for the contention that WNV can lead to autoimmune disease arises from reports of patients presenting with various neuromuscular diseases that presumably involve autoimmune mechanisms (GBS, other demyelinating neu¬ropathies, myasthenia gravis, brachial plexopathies, stiff-person syndrome, and delayed or recurrent symptoms. Although there is no specific treatment or vaccine currently approved in humans, and the standard remains supportive care, drugs that can alter the cascade of immunobiochemical events leading to neuronal death may be potentially useful (high-dose corticosteroids, interferon preparations, and intravenous immune globulin containing WNV-specific antibodies. Human experience with these agents seems promising based on anecdotal

  17. Drug Repurposing: New Treatments for Zika Virus Infection?

    Science.gov (United States)

    Cheng, Feixiong; Murray, James L; Rubin, Donald H

    2016-11-01

    To date, no antiviral agents have been approved for treating Zika virus (ZIKV) infection. Two recent drug-repurposing studies published in Cell Host & Microbe and Nature Medicine demonstrated that screening FDA-approved drugs for antiviral activity is a promising strategy for identifying therapeutics with novel activity against ZIKV infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. ZIKA VIRUS INFECTION; VERTICAL TRANSMISSION AND FOETAL CONGENITAL ANOMALIES.

    Science.gov (United States)

    Abbasi, Aziz-un-Nisa

    2016-01-01

    Zika virus (ZIKV) is an arbovirus belonging to flaviviridae family that includes Dengue, West Nile, and Yellow Fever among others. Zika virus was first discovered in 1947 in Zika forest of Uganda. It is a vector borne disease, which has been sporadically reported mostly from Africa, Pacific islands and Southeast Asia since its discovery. ZIKV infection presents as a mild illness with symptoms lasting for several days to a week after the bite of an infected mosquito. Majority of the patients have low grade fever, rash, headaches, joints pain, myalgia, and flu like symptoms. Pregnant women are more vulnerable to ZIKV infection and serious congenital anomalies can occur in foetus through trans-placental transmission. The gestation at which infection is acquired is important. Zika virus infection acquired in early pregnancy poses greater risk. There is no evidence so far about transmission through breast milk. Foetal microcephaly, Gillian Barre syndrome and other neurological and autoimmune syndromes have been reported in areas where Zika outbreaks have occurred. As infection is usually very mild no specific treatment is required. Pregnant women may be advised to take rest, get plenty of fluids. For fever and pain they can take antipyretics like paracetamol. So far no specific drugs or vaccines are available against Zika Virus Infection so prevention is the mainstay against this diseases. As ZIKV infection is a vector borne disease, prevention can be a multi-pronged strategy. These entail vector control interventions, personal protection, environmental sanitation and health education among others.

  19. Distribution of hepatitis B virus infection in Namibia | Mhata | South ...

    African Journals Online (AJOL)

    Background. Namibia regards hepatitis B virus (HBV) infection as a public health problem and introduced hepatitis B vaccinations for infants during 2009. However, information on HBV infection in the country remains limited, and effective public health interventions may be compromised in the absence of adequate ...

  20. Dengue virus life cycle : viral and host factors modulating infectivity

    NARCIS (Netherlands)

    Rodenhuis-Zybert, Izabela A.; Wilschut, Jan; Smit, Jolanda M.

    Dengue virus (DENV 1-4) represents a major emerging arthropod-borne pathogen. All four DENV serotypes are prevalent in the (sub) tropical regions of the world and infect 50-100 million individuals annually. Whereas the majority of DENV infections proceed asymptomatically or result in self-limited

  1. Prevalence of hepatitis B virus (HBV) infection among Makerere ...

    African Journals Online (AJOL)

    Abstract. Background: Medical students in the course of their clinical work are at risk of acquiring hepatitis B virus (HBV) infection or transmitting it to their patients. ... Risk factors associated HBV infection included having a sexual relationship, accidental needlestick injuries, and unprotected exposure to patients' body fluids.

  2. Hepatitis C virus infection in patients with oral lichen planus ...

    African Journals Online (AJOL)

    Background: Lichen planus (LP) is a chronic mucocutaneous disease of uncertain etiology. Recent reports suggest that LP is an extrahepatic manifestation of Hepatitis C infection. Objective: To determine the association of Hepatitis C virus (HCV) infection with oral LP and to study the tests of liver function in patients with ...

  3. Experimental infection of squirrel monkeys with nipah virus.

    Science.gov (United States)

    Marianneau, Philippe; Guillaume, Vanessa; Wong, Thong; Badmanathan, Munisamy; Looi, Ren Yih; Murri, Severine; Loth, Philippe; Tordo, Noel; Wild, Fabian; Horvat, Branka; Contamin, Hugues

    2010-03-01

    We infected squirrel monkeys (Saimiri sciureus) with Nipah virus to determine the monkeys' suitability for use as primate models in preclinical testing of preventive and therapeutic treatments. Infection of squirrel monkeys through intravenous injection was followed by high death rates associated with acute neurologic and respiratory illness and viral RNA and antigen production.

  4. The prevalence of hepatitis B virus infection in Nigerian children ...

    African Journals Online (AJOL)

    Introduction: Hepatitis B virus infection is a major global health problem of public health importance. In a bid to control the infection, the Nigerian government in 2004 introduced hepatitis B vaccine into the National Program on Immunization. There are no studies on the prevalence of hepatitis B in adolescent prior to 2004.

  5. Case Report: Varicella zoster virus infection causing urinary ...

    African Journals Online (AJOL)

    An 11-year-old boy receiving antiretroviral therapy for HIV infection and antibacterial therapy for pulmonary tuberculosis presented with urinary retention due to varicella zoster virus infection involving the sacral nerves, confirmed on serological testing. The perineum over dermatomes S2 - S4 on the left was involved with a ...

  6. Fracture risk in hepatitis C virus infected persons

    DEFF Research Database (Denmark)

    Hansen, Ann-Brit Eg; Omland, Lars Haukali; Krarup, Henrik

    2014-01-01

    BACKGROUND & AIMS: The association between Hepatitis C virus (HCV)-infection and fracture risk is not well characterized. We compared fracture risk between HCV-seropositive (HCV-exposed) patients and the general population and between patients with cleared and chronic HCV-infection. METHODS...

  7. Alpha-Fetoprotein in Asymptomatic Hepatitis B Virus Infected Subjects

    African Journals Online (AJOL)

    The prevalence of hepatitis B virus (HBV) infection is high in sub-Saharan Africa. A great number of the infected individuals are asymptomatic and are commonly diagnosed by chance. Alpha-fetoprotein and liver function tests were evaluated in asymptomatic hepatitis B surface antigen (HBsAg) positive subjects to ascertain ...

  8. Therapy for respiratory tract infections caused by respiratory syncytial virus

    NARCIS (Netherlands)

    van Woensel, J.; Kimpen, J.

    2000-01-01

    Respiratory syncytial virus (RSV) is the most common viral cause of lower respiratory tract infection (LRTI) in infancy and young children. No effective treatment for RSV lower respiratory tract infection (RSV-LRTI) exists. Ribavirin initially proved to be an effective anti-viral drug for RSV-LTRI.

  9. Therapy for respiratory tract infections caused by respiratory syncytial virus

    NARCIS (Netherlands)

    van Woensel, J; Kimpen, J

    Respiratory syncytial virus (RSV) is the most common viral cause of lower respiratory tract infection (LRTI) in infancy and young children. No effective treatment for RSV lower respiratory tract infection (RSV-LRTI) exists. Ribavirin initially proved to be an effective anti-viral drug for RSV-LTRI.

  10. Pathogenesis of herpes simplex virus infections of the cornea

    NARCIS (Netherlands)

    J. Maertzdorf (Jeroen)

    2002-01-01

    textabstractThe identification of human herpes virus (HHV) infections can be traced back to ancient Greece where Herpes simplex vims (HSV) infections in humans were first documented. Hippocrates used the word "herpes", meaning to creep or crawl, to describe spreading skin lesions. Although the

  11. Hepatitis C virus infection in Saudi Arabian recipients of renal ...

    African Journals Online (AJOL)

    conclusions in regard to the clinical impact of hepatitis C virus [HCV] infection. ... HCV infection and assessed its effect on patient and graft survival and occurrence of chronic hepatitis in renal transplant ... at the time of censorship was compared with the rates in 99 hemodialyzed patients, 400 healthy volunteers and 113

  12. Wheeze after Hospitalization for Respiratory Syncytial Virus Infection in Children

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Simonsen, Jacob; Breindahl, Morten

    2017-01-01

    Introduction Prior studies found associations between respiratory syncytial virus (RSV) infection, wheezing, and asthma. The present study aimed to examine the risk of wheezing after RSV, by the history of wheezing. Methods We included 39 children hospitalized for RSV infection (cases) and 23...

  13. Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus

    OpenAIRE

    Dejnirattisai, W; Supasa, P; Wongwiwat, W.; Rouvinski, A.; Barba-Spaeth, G.; Duangchinda, T; Sakuntabhai, A; Cao-Lormeau, VM; Malasit, P; REY, FA; Mongkolsapaya, J; Screaton, GR

    2016-01-01

    Zika virus (ZIKV) was discovered in 1947 and was thought to lead to relatively mild disease. The recent explosive outbreak of ZIKV in South America has led to widespread concern, with reports of neurological sequelae ranging from Guillain Barr? syndrome to microcephaly. ZIKV infection has occurred in areas previously exposed to dengue virus (DENV), a flavivirus closely related to ZIKV. Here we investigated the serological cross-reaction between the two viruses. Plasma immune to DENV showed su...

  14. 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.

  15. 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.

  16. Epstein Barr virus: Diseases linked to Infection and Transformation

    Directory of Open Access Journals (Sweden)

    Hem Chandra Jha

    2016-10-01

    Full Text Available Epstein-Barr virus (EBV was first discovered in 1964, and was the first known human tumor virus now shown to be associated with a vast number of human diseases. Numerous studies have been conducted to understand infection, propagation and transformation in various cell types linked to human diseases. However, a comprehensive lens through which virus infection, reactivation and transformation of infected host cells can be visualized is yet to be formally established and will need much further investigation. Several human cell types infected by EBV have been linked to associated diseases. However, whether these are a direct result of EBV infection or indirectly due to contributions by additional infectious agents will need to be fully investigated. Therefore, a thorough examination of infection, reactivation and cell transformation induced by EBV will provide a more detailed view of its contributions that drive pathogenesis. This undoubtedly expand our knowledge of the biology of EBV infection and the signaling activities of targeted cellular factors dysregulated on infection. Furthermore, these insights may lead to identification of therapeutic targets and agents for clinical interventions. Here we review the spectrum of EBV-associated diseases, the role of the encoded latent antigens, and the switch to latency or lytic replication which occurs in EBV infected cells. Furthermore, we describe the cellular processes and critical factors which contribute to cell transformation. We also describe the fate of B-cells and epithelial cells after EBV infection and the expected consequences which contribute to establishment of viral-associated pathologies.

  17. Epstein–Barr Virus: Diseases Linked to Infection and Transformation

    Science.gov (United States)

    Jha, Hem C.; Pei, Yonggang; Robertson, Erle S.

    2016-01-01

    Epstein–Barr virus (EBV) was first discovered in 1964, and was the first known human tumor virus now shown to be associated with a vast number of human diseases. Numerous studies have been conducted to understand infection, propagation, and transformation in various cell types linked to human diseases. However, a comprehensive lens through which virus infection, reactivation and transformation of infected host cells can be visualized is yet to be formally established and will need much further investigation. Several human cell types infected by EBV have been linked to associated diseases. However, whether these are a direct result of EBV infection or indirectly due to contributions by additional infectious agents will need to be fully investigated. Therefore, a thorough examination of infection, reactivation, and cell transformation induced by EBV will provide a more detailed view of its contributions that drive pathogenesis. This undoubtedly expand our knowledge of the biology of EBV infection and the signaling activities of targeted cellular factors dysregulated on infection. Furthermore, these insights may lead to identification of therapeutic targets and agents for clinical interventions. Here, we review the spectrum of EBV-associated diseases, the role of the encoded latent antigens, and the switch to latency or lytic replication which occurs in EBV infected cells. Furthermore, we describe the cellular processes and critical factors which contribute to cell transformation. We also describe the fate of B-cells and epithelial cells after EBV infection and the expected consequences which contribute to establishment of viral-associated pathologies. PMID:27826287

  18. Analysis of VSV pseudotype virus infection mediated by rubella virus envelope proteins

    National Research Council Canada - National Science Library

    Masafumi Sakata; Hideki Tani; Masaki Anraku; Michiyo Kataoka; Noriyo Nagata; Fumio Seki; Maino Tahara; Noriyuki Otsuki; Kiyoko Okamoto; Makoto Takeda; Yoshio Mori

    2017-01-01

    .... To establish an infection the host cells must be susceptible and permissible. To assess the susceptibility of individual cell lines, we generated a pseudotype vesicular stomatitis virus bearing RV envelope proteins (VSV-RV/CE2E1...

  19. Cystic encephalomalacia and intrauterine herpes simplex virus infection.

    Science.gov (United States)

    Gray, P H; Tudehope, D I; Masel, J

    1992-01-01

    Cystic encephalomalacia occurred in two preterm infants who had proven intrauterine herpes simplex virus type 2 infection. Calcification was evident in the basal ganglia. Follow-up scans indicated that the cysts had resolved over a period of two months in one infant, while in the case of the other, the cysts became progressively larger with significant ventricular dilatation developing. While cystic changes in the brain of preterm infants are usually due to periventricular leukomalacia, intrauterine infection needs to be considered as a possible cause. Antiviral treatment may be of benefit to infants with herpes simplex virus infection.

  20. Hepatitis B Virus and Human Immunodeficiency Virus co-infection in ...

    African Journals Online (AJOL)

    Hepatitis B Virus(HBV) and Human Immunodeficiency Virus(HIV) share similar properties such as modes of transmission. This study was therefore designed to find out the prevalence of HBV/HIV co-infection in Zawan village. Three hundred subjects were recruited into the study through simple random sampling method ...

  1. Identification of a pegivirus (GB virus-like virus) that infects horses

    DEFF Research Database (Denmark)

    Kapoor, Amit; Simmonds, Peter; Cullen, John M

    2013-01-01

    The recent identification of nonprimate hepaciviruses in dogs and then in horses prompted us to look for pegiviruses (GB virus-like viruses) in these species. Although none were detected in canines, we found widespread natural infection of horses by a novel pegivirus. Unique genomic features...

  2. Virus and host factors affecting the clinical outcome of Bluetongue Virus infection

    NARCIS (Netherlands)

    Caporale, M.; Gialleonorado, L.; Janowicz, A.; Wilkie, G.; Shaw, A.; Savini, G.; Rijn, van P.A.; Mertens, P.; Ventura, M.; Palmarini, M.

    2014-01-01

    Bluetongue is a major infectious disease of ruminants caused by bluetongue virus (BTV), an arbovirus transmitted by Culicoides. Here, we assessed virus and host factors influencing the clinical outcome of BTV infection using a single experimental framework. We investigated how mammalian host

  3. 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.

  4. Acute hepatitis A virus infections in British Gurkha soldiers.

    Science.gov (United States)

    Green, Chris A; Ross, D A; Bailey, M S

    2013-09-01

    Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections are endemic in most developing countries, including Nepal and Afghanistan, and may cause outbreaks in military personnel. Previously, more than 99% of new British Gurkha recruits were already immune to HAV because of prior infection, but this may be declining due to improved living conditions in their countries of origin. Acute HAV infections have occurred in Gurkha soldiers serving in Afghanistan, which made them unfit for duty for 2-3 months. In one case, early serological diagnosis was impeded by IgM results against both HAV and HEV that were caused by cross-reactivity or persistence from a previous infection. These cases have led to a policy change whereby all Gurkha recruits are now tested for previous HAV infection and if negative they are offered vaccination. Meanwhile, HEV infection remains a significant threat in Nepal and Afghanistan with low levels of background immunity and no commercially available vaccine.

  5. Respiratory viruses and torque teno virus in adults with acute respiratory infections.

    Science.gov (United States)

    Prasetyo, Afiono Agung; Desyardi, Martinus Nuherwan; Tanamas, Jimmy; Suradi; Reviono; Harsini; Kageyama, Seiji; Chikumi, Hiroki; Shimizu, Eiji

    2015-01-01

    To define the molecular epidemiology of respiratory viral infections in adult patients. Nasal and throat swabs were collected from all adult patients with influenza-like illness (ILI), acute respiratory infection (ARI), or severe ARI (SARI) admitted to a tertiary hospital in Surakarta, Indonesia, between March 2010 and April 2011 and analyzed for 19 respiratory viruses and for torque teno virus (TTV) and human gyrovirus (HGyV). Respiratory viruses were detected in 61.3% of the subjects, most of whom had ARI (90.8%, OR = 11.39), were hospitalized (96.9%, OR = 22.31), had asthma exacerbation (90.9%, OR = 8.67), and/or had pneumonia (80%, OR = 4.0). Human rhinovirus (HRV) A43 predominated. Influenza A H3N2, human metapneumovirus (HMPV) subtypes A1 and A2, the influenza B virus, human adenovirus B, and human coronavirus OC43 were also detected. All respiratory viruses were detected in the transition month between the rainy and dry seasons. No mixed respiratory virus infection was found. Coinfections of the influenza A H3N2 virus with TTV, HMPV with TTV, HRV with TTV, and human parainfluenza virus-3 with TTV were found in 4.7, 2.8, 19.8, and 0.9% of the samples, respectively. This study highlights the need to perform routine detection of respiratory viruses in adults hospitalized with ARI, asthma exacerbation, and/or pneumonia. © 2015 S. Karger AG, Basel

  6. Active Epstein-Barr virus infection after allogeneic stem cell transplantation : re-infection or reactivation?

    NARCIS (Netherlands)

    Meijer, E; Spijkers, S; Moschatsis, S; Boland, GJ; Thijsen, SFT; van Loon, AM; Verdonck, LF

    Recipients of allogeneic stem cell transplants (SCT) often show active Epstein-Barr virus (EBV) infection, which may progress to EBV-associated lymphoproliferative disorders. It is not known whether these EBV infections are true reactivations of the endogenous EBV strain or re-infections with an

  7. Chronic Ulcerative Herpes Simplex Virus Infection of the Vulva

    OpenAIRE

    Kelly Griffith-Bauer; Mary O’Hearn; Benjamin D. Ehst

    2012-01-01

    Herpes simplex virus infections in HIV-infected individuals can be clinically unusual and difficult to treat due to underlying problems with cell-mediated immunity and the occurrence of antiviral resistance. Additionally, partial or incomplete restoration of immune function may result in chronic ulcerations that require rotational treatments. In this report, we describe the case of a 38-year-old HIV-positive woman who developed the ulcerative form of chronic herpes simplex infection despite h...

  8. Chronic hepatitis C virus infection, a new cardiovascular risk factor?

    OpenAIRE

    Domont, Fanny; Cacoub, Patrice

    2016-01-01

    International audience; Among the large scope of extrahepatic manifestations related to hepatitis C virus (HCV) infection, many studies recently evaluated the frequency and characteristics of cardiovascular involvement. To assess the current published data on HCV infection and cardiovascular diseases. Published studies on cardiovascular disease, i.e. cerebrovascular accident and ischaemic heart disease in subjects with HCV infection were analysed from literature databases. Subjects with HCV c...

  9. Hepatitis C Virus Infection and Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Ayten Kadanali; Ahmet Ozbek; Leyla Saglam; Serpill Erol

    2009-01-01

    Background and Aims: A growing pile of evidence supports the notion that pulmonary involvement is one of the extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. The objective of this study was to determine the prevalence of HCV infection in patients with chronic obstructive pulmonary disease (COPD), and vice versa.Methods: Two cross-sectional studies were performed: 1. A prevalence study of HCV infection among patients with COPD; 2. A prevalence study of COPD among patie...

  10. Enhanced infectivity of bluetongue virus in cell culture by centrifugation.

    OpenAIRE

    Sundin, D R; Mecham, J.O.

    1989-01-01

    The effects of centrifugation of the infection of cell culture with bluetongue virus (BTV) were investigated. Baby hamster kidney cells were infected with BTV with or without centrifugation. Viral antigen was detected by immunofluorescence at 24 h in both centrifuged and noncentrifuged cultures. However, after 24 h of infection, the production of PFU in centrifuged cell cultures was 10- to 20-fold greater than that seen in cultures not centrifuged. In addition, centrifugation enhanced the dir...

  11. Reye's syndrome associated with respiratory syncytial virus infection.

    Science.gov (United States)

    Griffin, N; Keeling, J W; Tomlinson, A H

    1979-01-01

    An upper respiratory tract infection in a 22-month-old boy was followed by rapid loss of consciousness, hypoglycaemia, uraemia, and death. Necropsy examination showed fatty change of liver and kidneys, severe cerebral oedema, bronchiolitis, and endocardial fibroelastosis affecting the left ventricle. Immunofluorescence staining showed infection with respiratory syncytial virus (RSV). The clinical and pathological findings were those of Reye's syndrome, not previously reported accompanying RSV infection. Images Figure PMID:420528

  12. Experimental Hendra virus infection of dogs: virus replication, shedding and potential for transmission.

    Science.gov (United States)

    Middleton, D J; Riddell, S; Klein, R; Arkinstall, R; Haining, J; Frazer, L; Mottley, C; Evans, R; Johnson, D; Pallister, J

    2017-01-01

    Characterisation of experimental Hendra virus (HeV) infection in dogs and assessment of associated transmission risk. Beagle dogs were exposed oronasally to Hendra virus/Australia/Horse/2008/Redlands or to blood collected from HeV-infected ferrets. Ferrets were exposed to oral fluids collected from dogs after canine exposure to HeV. Observations made and samples tested post-exposure were used to assess the clinical course and replication sites of HeV in dogs, the infectivity for ferrets of canine oral fluids and features of HeV infection in dogs following contact with infective blood. Dogs were reliably infected with HeV and were generally asymptomatic. HeV was re-isolated from the oral cavity and virus clearance was associated with development of virus neutralising antibody. Major sites of HeV replication in dogs were the tonsils, lower respiratory tract and associated lymph nodes. Virus replication was documented in canine kidney and spleen, confirming a viraemic phase for canine HeV infection and suggesting that urine may be a source of infectious virus. Infection was transmitted to ferrets via canine oral secretions, with copy numbers for the HeV N gene in canine oral swabs comparable to those reported for nasal swabs of experimentally infected horses. HeV is not highly pathogenic for dogs, but their oral secretions pose a potential transmission risk to people. The time-window for transmission risk is circumscribed and corresponds to the period of acute infection before establishment of an adaptive immune response. The likelihood of central nervous system involvement in canine HeV infection is unclear, as is any long-term consequence. © 2017 Australian Veterinary Association.

  13. Why Zika virus infection has become a public health concern?

    Science.gov (United States)

    Chen, Hui-Lan; Tang, Ren-Bin

    2016-04-01

    Prior to 2015, Zika Virus (ZIKV) outbreaks had occurred in areas of Africa, Southeast Asia, and the Pacific Islands. Although a causal relationship between Zika infection during pregnancy and microcephaly is strongly suspected, such a connection has not yet been scientifically proven. In May 2015, the outbreak of ZIKV infection in Brazil led to reports of syndrome and pregnant women giving birth to babies with birth defects and poor pregnancy outcomes; the Pan American Health Organization (PAHO) issued an alert regarding the first confirmed ZIKV infection in Brazil. Currently, ZIKV outbreaks are ongoing and it will be difficult to predict how the virus will spread over time. ZIKV is transmitted to humans primarily through the bite of infected mosquitos, Aedes aegypti and Aedes albopictus. These mosquitoes are the principle vectors of dengue, and ZIKV disease generally is reported to include symptoms associated with acute febrile illnesses that clinically resembles dengue fever. The laboratory diagnosis can be performed by using reverse-transcriptase polymerase chain reaction (RT-PCR) on serum, viral nucleic acid and virus-specific immunoglobulin M. There is currently no vaccine and antiviral treatment available for ZIKV infection, and the only way to prevent congenital ZIKV infection is to prevent maternal infection. In February 2016, the Taiwan Centers for Disease Control (Taiwan CDC) activated ZIKV as a Category V Notifiable Infectious Disease similar to Ebola virus disease and MERS. Copyright © 2016. Published by Elsevier Taiwan LLC.

  14. African green monkey TRIM5α restriction in simian immunodeficiency virus-specific rhesus macaque effector CD4 T cells enhances their survival and antiviral function.

    Science.gov (United States)

    Jain, Sumiti; Trivett, Matthew T; Ayala, Victor I; Ohlen, Claes; Ott, David E

    2015-04-01

    The expression of xenogeneic TRIM5α proteins can restrict infection in various retrovirus/host cell pairings. Previously, we have shown that African green monkey TRIM5α (AgmTRIM5α) potently restricts both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus mac239 (SIV(mac239)) replication in a transformed human T-cell line (L. V. Coren, et al., Retrovirology 12:11, 2015, http://dx.doi.org/10.1186/s12977-015-0137-9). To assess AgmTRIM5α restriction in primary cells, we transduced AgmTRIM5α into primary rhesus macaque CD4 T cells and infected them with SIV(mac239). Experiments with T-cell clones revealed that AgmTRIM5α could reproducibly restrict SIV(mac239) replication, and that this restriction synergizes with an intrinsic resistance to infection present in some CD4 T-cell clones. AgmTRIM5α transduction of virus-specific CD4 T-cell clones increased and prolonged their ability to suppress SIV spread in CD4 target cells. This increased antiviral function was strongly linked to decreased viral replication in the AgmTRIM5α-expressing effectors, consistent with restriction preventing the virus-induced cytopathogenicity that disables effector function. Taken together, our data show that AgmTRIM5α restriction, although not absolute, reduces SIV replication in primary rhesus CD4 T cells which, in turn, increases their antiviral function. These results support prior in vivo data indicating that the contribution of virus-specific CD4 T-cell effectors to viral control is limited due to infection. The potential of effector CD4 T cells to immunologically modulate SIV/HIV infection likely is limited by their susceptibility to infection and subsequent inactivation or elimination. Here, we show that AgmTRIM5α expression inhibits SIV spread in primary effector CD4 T cells in vitro. Importantly, protection of effector CD4 T cells by AgmTRIM5α markedly enhanced their antiviral function by delaying SIV infection, thereby extending their viability

  15. Infectivity of Deinbollia mosaic virus, a novel weed-infecting begomovirus in East Africa.

    Science.gov (United States)

    Kyallo, Martina; Ateka, Elijah Miinda; Sseruwagi, Peter; Ascencio-Ibáñez, José Trinidad; Ssemakula, Mildred-Ochwo; Skilton, Robert; Ndunguru, Joseph

    2017-11-01

    Weed-infecting begomoviruses play an important role in the epidemiology of crop diseases because they can potentially infect crops and contribute to the genetic diversity of crop-infecting begomoviruses. Despite the important epidemiological role that weed-infecting begomoviruses play, they remain insufficiently studied in Africa. Recently, we identified Deinbollia mosaic virus (DMV), a distinct begomovirus found naturally infecting the weed host Deinbollia borbonica (Sapindaceae) in Kenya and Tanzania. In this study, we investigated the capacity of DMV to infect a restricted host range of Solanaceae and Euphorbiaceae species. Biolistic inoculation of Nicotiana benthamiana with concatemeric DNAs resulted in systemic infection associated with yellow mosaic symptoms, while DNA partial dimers caused asymptomatic systemic infection. DMV was not infectious to cassava (Manihot esculenta Crantz), suggesting host resistance to the virus. Here, we demonstrate the first experimental infectivity analysis of DMV in N. benthamiana and cassava.

  16. Interferon Response in Hepatitis C Virus (HCV Infection: Lessons from Cell Culture Systems of HCV Infection

    Directory of Open Access Journals (Sweden)

    Pil Soo Sung

    2015-10-01

    Full Text Available Hepatitis C virus (HCV is a positive-stranded RNA virus that infects approximately 130–170 million people worldwide. In 2005, the first HCV infection system in cell culture was established using clone JFH-1, which was isolated from a Japanese patient with fulminant HCV infection. JFH-1 replicates efficiently in hepatoma cells and infectious virion particles are released into the culture supernatant. The development of cell culture-derived HCV (HCVcc systems has allowed us to understand how hosts respond to HCV infection and how HCV evades host responses. Although the mechanisms underlying the different outcomes of HCV infection are not fully understood, innate immune responses seem to have a critical impact on the outcome of HCV infection, as demonstrated by the prognostic value of IFN-λ gene polymorphisms among patients with chronic HCV infection. Herein, we review recent research on interferon response in HCV infection, particularly studies using HCVcc infection systems.

  17. Chronic Δ9-Tetrahydrocannabinol Administration Reduces IgE+B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin

    OpenAIRE

    Qin, CHUN-CHUNG; Molina, P; Liu, L; Cong, Z; Wu, X; Wang, H; Chen, Z; Wei, Q

    2016-01-01

    Delta9-tetrahydrocannabinol (Δ9-THC) is the major psychoactive component of the cannabis plant. Δ9-THC has been used in the active ingredient of Marinol as an appetite stimulant for AIDS patients. Its impact on progression of HIV-1 infection, however, remains debatable. Previous studies indicated that Δ9-THC administration enhanced HIV-1 infection in huPBL-SCID mice but seemingly decreased early mortality in simian immunodeficiency virus (SIV) infected male Indian-derived rhesus macaques. Her...

  18. Screening Criteria for Ophthalmic Manifestations of Congenital Zika Virus Infection.

    Science.gov (United States)

    Zin, Andrea A; Tsui, Irena; Rossetto, Julia; Vasconcelos, Zilton; Adachi, Kristina; Valderramos, Stephanie; Halai, Umme-Aiman; Pone, Marcos Vinicius da Silva; Pone, Sheila Moura; Silveira Filho, Joel Carlos Barros; Aibe, Mitsue S; da Costa, Ana Carolina C; Zin, Olivia A; Belfort, Rubens; Brasil, Patricia; Nielsen-Saines, Karin; Moreira, Maria Elisabeth Lopes

    2017-09-01

    Current guidelines recommend screening eye examinations for infants with microcephaly or laboratory-confirmed Zika virus infection but not for all infants potentially exposed to Zika virus in utero. To evaluate eye findings in a cohort of infants whose mothers had polymerase chain reaction-confirmed Zika virus infection during pregnancy. In this descriptive case series performed from January 2 through October 30, 2016, infants were examined from birth to 1 year of age by a multidisciplinary medical team, including a pediatric ophthalmologist, from Fernandes Figueira Institute, a Ministry of Health referral center for high-risk pregnancies and infectious diseases in children in Rio de Janeiro, Brazil. Mother-infant pairs from Rio de Janeiro, Brazil, who presented with suspected Zika virus infection during pregnancy were referred to our institution and had serum, urine, amniotic fluid, or placenta samples tested by real-time polymerase chain reaction for Zika virus. Description of eye findings, presence of microcephaly or other central nervous system abnormalities, and timing of infection in infants with confirmed Zika virus during pregnancy. Eye abnormalities were correlated with central nervous system findings, microcephaly, and the timing of maternal infection. Of the 112 with polymerase chain reaction-confirmed Zika virus infection in maternal specimens, 24 infants (21.4%) examined had eye abnormalities (median age at first eye examination, 31 days; range, 0-305 days). Ten infants (41.7%) with eye abnormalities did not have microcephaly, and 8 (33.3%) did not have any central nervous system findings. Fourteen infants with eye abnormalities (58.3%) were born to women infected in the first trimester, 8 (33.3%) in the second trimester, and 2 (8.3%) in the third trimester. Optic nerve and retinal abnormalities were the most frequent findings. Eye abnormalities were statistically associated with microcephaly (odds ratio [OR], 19.1; 95% CI, 6.0-61.0), other central

  19. Behavioral, metabolic, and immune consequences of chronic alcohol or cannabinoids on HIV/AIDs: Studies in the Non-Human Primate SIV model

    Science.gov (United States)

    Molina, Patricia E.; Amedee, Angela M.; Winsauer, Peter; Nelson, Steve; Bagby, Gregory; Simon, Liz

    2015-01-01

    HIV-associated mortality has been significantly reduced with antiretroviral therapy (ART), and HIV infection has become a chronic disease that frequently coexists with many disorders, including substance abuse (Azar et al. 2010; Phillips et al. 2001). Alcohol and drugs of abuse may modify host-pathogen interactions at various levels including behavioral, metabolic, and immune consequences of HIV infection, as well as the ability of the virus to integrate into the genome and replicate in host cells. Identifying mechanisms responsible for these interactions is complicated by many factors, such as the tissue specific responses to viral infection, multiple cellular mechanisms involved in inflammatory responses, neuroendocrine and localized responses to infection, and kinetics of viral replication. An integrated physiological analysis of the biomedical consequences of chronic alcohol and drug use or abuse on disease progression is possible using rhesus macaques infected with simian immunodeficiency virus (SIV), a relevant model of HIV infection. This review will provide an overview of the data gathered using this model to show that chronic administration of two of the most commonly abused substances, alcohol and cannabinoids (Δ9-Tetrahydrocannabinol; THC), affect host-pathogen interactions. PMID:25795088

  20. Establishment of a Vero cell line persistently infected with African swine fever virus.

    OpenAIRE

    Salas, J; Viñuela, E

    1986-01-01

    A Vero cell line persistently infected with African swine fever virus was established by infecting the cells in the presence of 10 mM NH4Cl (Vero-P cell line). The virus derived from the Vero-P cultures infected Vero cells, and virus titers were comparable to those obtained in Vero cells acutely infected with African swine fever virus. The structural proteins of the virus from Vero-P cells were similar to those of the virus produced in lytic infections. Virus production was low when the Vero-...

  1. Dengue Infection in a Human Immunodeficiency Virus-1 Positive Patient Chronically Infected with Hepatitis B Virus in Western Mexico.

    Science.gov (United States)

    Delgado-Enciso, Iván; Espinoza-Gómez, Francisco; Ochoa-Jiménez, Rodolfo; Valle-Reyes, Salvador; Vásquez, Clemente; López-Lemus, Uriel A

    2017-01-11

    Human immunodeficiency virus (HIV) and dengue coinfection has not been extensively studied. We report herein a case of dengue serotype 1 infection in an HIV-1-positive patient coinfected with hepatitis B virus (HBV) in Colima State, Mexico. CD4+ cells and HIV-1 viremia remained at normal levels, and no severe complications were observed during this multiple viral infection. The alanine transaminase and aspartate transaminase values were elevated before and during dengue infection. Surprisingly, these parameters were significantly reduced 2 months later. Because of the lack of evidence regarding this multiple viral interaction, further research is required to understand the biologic and clinical course of dengue infection in HIV-1/HBV coinfected patients, especially in tropical regions where dengue virus transmission is highly active. © The American Society of Tropical Medicine and Hygiene.

  2. Pathogenesis of Lassa fever virus infection: I. Susceptibility of mice to recombinant Lassa Gp/LCMV chimeric virus.

    Science.gov (United States)

    Lee, Andrew M; Cruite, Justin; Welch, Megan J; Sullivan, Brian; Oldstone, Michael B A

    2013-08-01

    Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. Inoculation of immunocompetent adults resulted in an acute infection, generation of virus-specific CD8(+) T cells and clearance of the infection. Inoculation of newborn mice with rLCMV Cl13/LASV Gp resulted in a life-long persistent infection. Interestingly, adoptive transfer of rLCMV Cl13/LASV Gp immune memory cells into such persistently infected mice failed to purge virus but, in contrast, cleared virus from mice persistently infected with wt LCMV Cl13. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Characterization of a new simian immunodeficiency virus strain in a naturally infected Pan troglodytes troglodytes chimpanzee with AIDS related symptoms

    Directory of Open Access Journals (Sweden)

    Aghokeng Avelin F

    2011-01-01

    Full Text Available Abstract Background Data on the evolution of natural SIV infection in chimpanzees (SIVcpz and on the impact of SIV on local ape populations are only available for Eastern African chimpanzee subspecies (Pan troglodytes schweinfurthii, and no data exist for Central chimpanzees (Pan troglodytes troglodytes, the natural reservoir of the ancestors of HIV-1 in humans. Here, we report a case of naturally-acquired SIVcpz infection in a P.t.troglodytes chimpanzee with clinical and biological data and analysis of viral evolution over the course of infection. Results A male chimpanzee (Cam155, 1.5 years, was seized in southern Cameroon in November 2003 and screened SIV positive during quarantine. Clinical follow-up and biological analyses have been performed for 7 years and showed a significant decline of CD4 counts (1,380 cells/mm3 in 2004 vs 287 in 2009, a severe thrombocytopenia (130,000 cells/mm3 in 2004 vs 5,000 cells/mm3 in 2009, a weight loss of 21.8% from August 2009 to January 2010 (16 to 12.5 kg and frequent periods of infections with diverse pathogens. DNA from PBMC, leftover from clinical follow-up samples collected in 2004 and 2009, was used to amplify overlapping fragments and sequence two full-length SIVcpzPtt-Cam155 genomes. SIVcpzPtt-Cam155 was phylogenetically related to other SIVcpzPtt from Cameroon (SIVcpzPtt-Cam13 and Gabon (SIVcpzPtt-Gab1. Ten molecular clones 5 years apart, spanning the V1V4 gp120 env region (1,100 bp, were obtained. Analyses of the env region showed positive selection (dN-dS >0, intra-host length variation and extensive amino acid diversity between clones, greater in 2009. Over 5 years, N-glycosylation site frequency significantly increased (p Conclusions Here, we describe for the first time the clinical history and viral evolution of a naturally SIV infected P.t.troglodytes chimpanzee. The findings show an increasing viral diversity over time and suggest clinical progression to an AIDS-like disease, showing that

  4. Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients.

    Science.gov (United States)

    Alvarez-Muñoz, Ma Teresa; Maldonado-Rodriguez, Angelica; Rojas-Montes, Othon; Torres-Ibarra, Rocio; Gutierrez-Escolano, Fernanda; Vazquez-Rosales, Guillermo; Gomez, Alejandro; Muñoz, Onofre; Torres, Javier; Lira, Rosalia

    2014-10-07

    To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico. We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson's χ(2) and/or Fisher's exact test. We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05). The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV.

  5. Virus isolation for diagnosing dengue virus infections in returning travelers

    NARCIS (Netherlands)

    Teichmann, D.; Göbels, K.; Niedrig, M.; Sim-Brandenburg, J.-W.; Làge-Stehr, J.; Grobusch, M. P.

    2003-01-01

    Dengue fever is recognized as one of the most frequent imported acute febrile illnesses affecting European tourists returning from the tropics. In order to assess the value of virus isolation for the diagnosis of dengue fever, 70 cases of dengue fever confirmed in German travelers during the period

  6. Towards antiviral therapies for treating dengue virus infections.

    Science.gov (United States)

    Kaptein, Suzanne Jf; Neyts, Johan

    2016-10-01

    Dengue virus is an emerging human pathogen that poses a huge public health burden by infecting annually about 390 million individuals of which a quarter report with clinical manifestations. Although progress has been made in understanding dengue pathogenesis, a licensed vaccine or antiviral therapy against this virus is still lacking. Treatment of patients is confined to symptomatic alleviation and supportive care. The development of dengue therapeutics thus remains of utmost importance. This review focuses on the few molecules that were evaluated in dengue virus-infected patients: balapiravir, chloroquine, lovastatin, prednisolone and celgosivir. The lessons learned from these clinical trials can be very helpful for the design of future trials for the next generation of dengue virus inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Regional aggressive root resorption caused by neuronal virus infection

    DEFF Research Database (Denmark)

    Kjær, Inger; Strøm, Carsten; Worsaae, Nils

    2012-01-01

    occurring regionally. Two cases of female patients, 26 and 28 years old, referred with aggressive root resorption were investigated clinically and radiographically. Anamnestic information revealed severe virus diseases during childhood, meningitis in one case and whooping cough in the other. One...... of the patients was treated with dental implants. Virus spreading along nerve paths is a possible explanation for the unexpected resorptions. In both cases, the resorptions began cervically. The extent of the resorption processes in the dentition followed the virus infected nerve paths and the resorption process...... stopped when reaching regions that were innervated differently and not infected by virus. In one case, histological examination revealed multinuclear dentinoclasts. The pattern of resorption in the two cases indicates that innervation is a factor, which under normal conditions may protect the root surface...

  8. Neonatal herpes simplex virus infection: epidemiology and treatment.

    Science.gov (United States)

    James, Scott H; Kimberlin, David W

    2015-03-01

    Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are highly prevalent viruses capable of establishing lifelong infection. Genital herpes in women of childbearing age represents a major risk for mother-to-child transmission (MTCT) of HSV infection, with primary and first-episode genital HSV infections posing the highest risk. The advent of antiviral therapy with parenteral acyclovir has led to significant improvement in neonatal HSV disease mortality. Further studies are needed to improve the clinician's ability to identify infants at increased risk for HSV infection and prevent MTCT, and to develop novel antiviral agents with increased efficacy in infants with HSV infection. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Pseudorabies virus infection alters neuronal activity and connectivity in vitro.

    Directory of Open Access Journals (Sweden)

    Kelly M McCarthy

    2009-10-01

    Full Text Available Alpha-herpesviruses, including human herpes simplex virus 1 & 2, varicella zoster virus and the swine pseudorabies virus (PRV, infect the peripheral nervous system of their hosts. Symptoms of infection often include itching, numbness, or pain indicative of altered neurological function. To determine if there is an in vitro electrophysiological correlate to these characteristic in vivo symptoms, we infected cultured rat sympathetic neurons with well-characterized strains of PRV known to produce virulent or attenuated symptoms in animals. Whole-cell patch clamp recordings were made at various times after infection. By 8 hours of infection with virulent PRV, action potential (AP firing rates increased substantially and were accompanied by hyperpolarized resting membrane potentials and spikelet-like events. Coincident with the increase in AP firing rate, adjacent neurons exhibited coupled firing events, first with AP-spikelets and later with near identical resting membrane potentials and AP firing. Small fusion pores between adjacent cell bodies formed early after infection as demonstrated by transfer of the low molecular weight dye, Lucifer Yellow. Later, larger pores formed as demonstrated by transfer of high molecular weight Texas red-dextran conjugates between infected cells. Further evidence for viral-induced fusion pores was obtained by infecting neurons with a viral mutant defective for glycoprotein B, a component of the viral membrane fusion complex. These infected neurons were essentially identical to mock infected neurons: no increased AP firing, no spikelet-like events, and no electrical or dye transfer. Infection with PRV Bartha, an attenuated circuit-tracing strain delayed, but did not eliminate the increased neuronal activity and coupling events. We suggest that formation of fusion pores between infected neurons results in electrical coupling and elevated firing rates, and that these processes may contribute to the altered neural

  10. [Three cases of suspected re-infection of mumps virus].

    Science.gov (United States)

    Hatanaka, Akio; Kamada, Tomoko; Honda, Keiji; Tazaki, Akihisa; Kishine, Naomi; Kawashima, Yoshiyuki

    2012-08-01

    A 32-year-old woman, 5-year-old girl, and 33-year-old man visited our otorhinolaryngology outpatient clinic with tumentia of the unilateral parotid gland. A high titer of serum IgG antibodies against the mumps virus was detected. Around the same time, other members of their families had the same parotid tumentia, and they were diagnosed as having their first mumps infection. Therefore, the diagnosis of the three cases was strongly suspected to be re-infection with mumps. In Japan, it was classically believed that the mumps virus infection occurs only once in patients and reinfection doesn't occur. However, some pediatricians in Japan have reported that re-infection with mumps is strongly suspected when high titers of serum IgG antibodies against the mumps virus are found at the initial visit. It is now believed many more examples of mumps re-infection cases have existed than we previously believed. When high titers of serum IgG antibodies against the mumps virus are detected at an initial visit in patients who have had mumps previously, re-infection should be strongly suspected. And to make it certain, we suggest that the mumps IgG antibodies should be checked twice to confirm the diagnosis. If elevation of the IgG antibodies persist, the diagnosis will be much more certain.

  11. Infection with influenza virus induces IL-33 in murine lungs.

    Science.gov (United States)

    Le Goffic, Ronan; Arshad, Muhammad Imran; Rauch, Michel; L'Helgoualc'h, Annie; Delmas, Bernard; Piquet-Pellorce, Claire; Samson, Michel

    2011-12-01

    IL-33, a novel IL-1 family member, is crucially expressed and involved in pulmonary diseases, but its regulation in viral diseases such as influenza A virus (IAV) remains unclear. This study aimed to characterize the expression and release of IL-33 in lungs of IAV-infected mice in vivo and in murine respiratory epithelial cells (MLE-15) in vitro. Our results provide evidence of up-regulation of IL-33 mRNA in IAV-infected murine lungs, compared with noninfected control mice. The overexpression of IL-33 was positively correlated with a significant increase in mRNA encoding the proinflammatory cytokines TNF-α, IFN-γ, IL-1β, and IL-6, and was also associated with an increase in IFN-β mRNA. A profound overexpression of IL-33 protein was evident in IAV-infected murine lungs and bronchoalveolar lavages of influenza-infected mice, compared with low concentrations in naive lungs in vivo. Immunolocalization highlighted the cellular expression of IL-33 in alveolar epithelial and endothelial cells, along with increased infiltrate cells in virus-infected lungs. Further in vitro experiments showed an induction of IL-33 transcript-in MLE-15 cells and human epithelial cells (A549) infected with different strains of IAV in comparison with noninfected cells. In conclusion, our findings evidenced a profound expression of IL-33 in lungs during both in vivo and in vitro IAV infections, suggesting a role for IL-33 in virus-induced lung infections.

  12. Hendra virus infection dynamics in Australian fruit bats.

    Science.gov (United States)

    Field, Hume; de Jong, Carol; Melville, Deb; Smith, Craig; Smith, Ina; Broos, Alice; Kung, Yu Hsin Nina; McLaughlin, Amanda; Zeddeman, Anne

    2011-01-01

    Hendra virus is a recently emerged zoonotic agent in Australia. Since first described in 1994, the virus has spilled from its wildlife reservoir (pteropid fruit bats, or 'flying foxes') on multiple occasions causing equine and human fatalities. We undertook a three-year longitudinal study to detect virus in the urine of free-living flying foxes (a putative route of excretion) to investigate Hendra virus infection dynamics. Pooled urine samples collected off plastic sheets placed beneath roosting flying foxes were screened for Hendra virus genome by quantitative RT-PCR, using a set of primers and probe derived from the matrix protein gene. A total of 1672 pooled urine samples from 67 sampling events was collected and tested between 1 July 2008 and 30 June 2011, with 25% of sampling events and 2.5% of urine samples yielding detections. The proportion of positive samples was statistically associated with year and location. The findings indicate that Hendra virus excretion occurs periodically rather than continuously, and in geographically disparate flying fox populations in the state of Queensland. The lack of any detection in the Northern Territory suggests prevalence may vary across the range of flying foxes in Australia. Finally, our findings suggest that flying foxes can excrete virus at any time of year, and that the apparent seasonal clustering of Hendra virus incidents in horses and associated humans (70% have occurred June to October) reflects factors other than the presence of virus. Identification of these factors will strengthen risk minimization strategies for horses and ultimately humans.

  13. Detection and diagnosis of rice-infecting viruses

    Directory of Open Access Journals (Sweden)

    Tamaki Uehara Ichiki

    2013-10-01

    Full Text Available Rice-infecting viruses have caused serious damage to rice production in Asian, American, and African countries, where about 30 rice viruses and diseases have been reported. To control these diseases, developing accurate, quick methods to detect and diagnose the viruses in the host plants and any insect vectors of the viruses is very important. Based on an antigen–antibody reaction, serological methods such as latex agglutination reaction (LAR and enzyme-linked immunosorbent assay (ELISA have advanced to detect viral particles or major proteins derived from viruses. They aid in forecasting disease and surveying disease spread and are widely used for virus detection at plant protection stations and research laboratories. From the early 2000s, based on sequence information for the target virus, several other methods such as reverse transcription-polymerase chain reaction (RT-PCR and reverse transcription- loop-mediated isothermal amplification (RT-LAMP have been developed that are sensitive, rapid, and able to differentiate closely related viruses. Recent techniques such as real-time RT-PCR can be used to quantify the pathogen in target samples and monitor population dynamics of a virus, and metagenomic analyses using next-generation sequencing and microarrays show potential for use in the diagnosis of rice diseases.

  14. Vaccinia Virus Infections in a Martial Arts Gym

    Centers for Disease Control (CDC) Podcasts

    2011-04-04

    This podcast discusses an outbreak of vaccinia virus in Maryland in 2008. Christine Hughes, a health scientist with the Poxvirus and Rabies Branch at CDC, and co-author of a paper in the April 2011 issue of CDC's journal, discusses vaccinia virus infections in a martial arts gym.  Created: 4/4/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 4/5/2011.

  15. 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...

  16. Cowpea viruses: Effect of single and mixed infections on symptomatology and virus concentration

    Directory of Open Access Journals (Sweden)

    Nsa Imade Y

    2007-09-01

    Full Text Available Abstract Natural multiple viral infections of cultivated cowpeas have been reported in Nigeria. In this study, three Nigerian commercial cowpea cultivars ("Olo 11", "Oloyin" and "White" and two lines from the IITA (IT86D- 719 and TVU 76 were mechanically inoculated with Cowpea aphid-borne mosaic virus (CABMV, Bean southern mosaic virus (SBMV and Cowpea mottle virus (CMeV singly, as well as in all possible combinations at 10, 20 and 30 days after planting (DAP. Samples of leaves or stems were collected at 10, 20 and 30 days after inoculation (DAI and analyzed for relative virus concentration by Enzyme-Linked Immunosrbent Assay. All the cultivars and lines {CVS/L} were susceptible to the viruses but the commercial CVS showed more severe symptoms and had relatively higher viral concentration. In single virus infections, CABMV which induced the most severe symptoms had absorbance values (at 405 nm of 0.11 to 0.46 while SBMV and CMeV which induced moderate symptoms had virus titre of 0.74 to 1.99 and 0.11 to 0.90 respectively. Plants inoculated 10 DAP had significantly higher virus concentration than those inoculated 30 DAP. In mixed infections involving CABMV (10 DAP apical necrosis and death were observed in commerci