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Vanessa M. Hirsch - One of the best experts on this subject based on the ideXlab platform.
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Characterization of a monoclonal anti-capsid antibody that cross-reacts with three major Primate Lentivirus lineages
Virology, 2011Co-Authors: Brigitte E. Sanders-beer, Vanessa M. Hirsch, Jonathan S. Allan, Magdalena Eschricht, Janna Seifried, Stephen NorleyAbstract:Abstract Mouse monoclonal antibodies with varying specificities against the Gag capsid of simian and human immunodeficiency virus (SIV/HIV) were generated by immunizing mice with whole inactivated SIVagmTYO-1. Monoclonal antibody AG3.0 showed the broadest reactivity recognizing the Gag capsid protein (p24–27) and Gag precursors p38, p55, and p150 of HIV-1, HIV-2, SIVmac, and SIVagm. Using overlapping peptides, the AG3.0 epitope was mapped in capsid to a sequence (SPRTLNA) conserved among HIV-1, HIV-2, SIVrcm, SIVsm/mac, and SIVagm related viruses. Because of its broad cross-reactivity, AG3.0 was used to develop an antigen capture assay with a lower detection limit of 100 pg/ml HIV-1 Gag p24. Interestingly, AG3.0 was found to have a faster binding on/off rate for SIVagmVer and SIVmac Gag than for SIVagmSab Gag, possibly due to differences outside the SPRTLNA motif. In addition, the ribonucleic acid (RNA) coding for AG3.0 was sequenced to facilitate the development of humanized monoclonal antibodies.
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Simian immunodeficiency viruses from multiple lineages infect human macrophages: implications for cross-species transmission.
Journal of acquired immune deficiency syndromes (1999), 2003Co-Authors: Tobias A. Grimm, Vanessa M. Hirsch, Brigitte Beer, Kathleen A. ClouseAbstract:Zoonotic transfer of simian immunodeficiency virus (SIV) from chimpanzees and sooty mangabeys to humans has been documented on at least seven occasions. Several recently identified SIV isolates have also been shown to replicate efficiently in human peripheral blood mononuclear cells (PBMCs) in vitro, indicative of the potential for additional cross-species transmission via T cell infection. Although SIV predominantly uses the macrophage-tropic HIV chemokine coreceptor CCR5, little is known about the ability of SIV to infect human macrophages. In this study, 16 SIV isolates belonging to five different Primate Lentivirus lineages were tested for their ability to infect human monocyte-derived macrophages (MDMs). Twelve of the viruses were capable of infecting MDMs, and 11 of these were also able to replicate in human PBMCs. The replication capacity of the isolates differed within and between the various families and was dependent on particular donor macrophages. Our results suggest that most simian Lentiviruses characterized to date not only have the ability to infect primary human T lymphocytes but also replicate efficiently in macrophages, thereby increasing the potential for cross-species transmission into the human population. Comparative studies using these isolates may facilitate the identification of characteristics that contribute to virus infectivity and pathogenicity.
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Origins and evolution of AIDS viruses: estimating the time-scale.
Biochemical Society transactions, 2000Co-Authors: Paul M. Sharp, Vanessa M. Hirsch, Feng Gao, Elizabeth Bailes, Brigitte E. Beer, Beatrice H. HahnAbstract:The Primate Lentiviruses comprise SIV strains from various host species, as well as two viruses, HIV-1 and HIV-2, that cause AIDS in humans. The origins of HIV-1 and HIV-2 have been traced to cross-species transmissions from chimpanzees and sooty mangabey monkeys respectively. Two approaches have been taken to estimate the time-scale of the evolution of these viruses. Certain groups of SIV strains appear to have evolved in a host-dependent manner, implying a time-scale of many thousands or even millions of years. In stark contrast, molecular clock calculations have previously been used to estimate a time-scale of only tens or hundreds of years. Those calculations largely ignored heterogeneity of evolutionary rates across different sites within sequences. In fact, the distribution of rates at different sites seems extremely skewed in HIV-1, and so the time-depth of the Primate Lentivirus evolutionary tree may have been underestimated by at least a factor of ten. However, these date estimates still seem to be far too recent to be consistent with host-dependent evolution.
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Phylogeny and natural history of the Primate Lentiviruses, SIV and HIV.
Current opinion in genetics & development, 1995Co-Authors: Vanessa M. Hirsch, George Dapolito, Robert Goeken, Barbara J. CampbellAbstract:Abstract Studies of Primate Lentivirus phylogeny over the past decade have established a minimum of five related, but genetically distinct, groups of simian immunodeficiency virus (SIV), each originating from a different African Primate species. The hypothesis that HIV-2 (and SIVmac) arose by cross-species transmission from sooty mangabeys (Cercocebus atys has been strengthened by a more detailed characterization of the SIVsm/SIVmac/HIV-2 group of viruses. SIV from all four subspecies of African green monkeys (SIVagm) have been characterized with an apparent chimeric genome structure of SIVagm from west African green monkeys. Although these naturally infected Primates remain healthy, cross-species transmission to other Primate species may result in immunodeficiency, as caused by SIVsm infection of macaque monkeys (Macaca sp.) and recently, SIVagm infection of pig-tailed macaques (M. nemestrina). Studies of variation within infected individuals have been facilitated by adaptation of the techniques of heteroduplex analysis and single-stranded conformational polymorphism of PCR generated fragments.
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A distinct African Lentivirus from Sykes' monkeys.
Journal of virology, 1993Co-Authors: Vanessa M. Hirsch, George Dapolito, Harold M. Mcclure, Patricia N. Fultz, Simoy Goldstein, P. Emau, Mohamed Isahakia, Rhoshel Lenroot, G. Myers, Philip R. JohnsonAbstract:Asymptomatic infection with simian immunodeficiency virus (SIV) has been demonstrated in African Sykes' monkeys (Cercopithecus mitis albogularis), and virus isolation confirmed infection with a novel SIV from Sykes' monkeys (SIVsyk). Macaques inoculated with SIVsyk became persistently infected but remained clinically healthy. We utilized polymerase chain reaction amplification to generate a full-length, infectious molecular clone of SIVsyk. The genome organization of SIVsyk is similar to that of the other Primate Lentiviruses, consisting of gag, pol, vif, vpr, tat, rev, env, and nef. A unique feature is the absence of the highly conserved NF-kappa B binding site in the long terminal repeat. SIVsyk is genetically equidistant from other Primate Lentiviruses. Thus, SIVsyk represents a new group that is distinct from the four previously recognized Primate Lentivirus groups: human immunodeficiency virus type 1 (HIV-1), SIV from sooty mangabeys (SIVsmm) and HIV-2, SIV from African green monkeys (SIVagm), and SIV from mandrills (SIVmnd). The genetic differences between SIVsyk and SIVagm, isolates derived from monkeys of the same genus, underscore the potential for other distinct SIVs which have yet to be isolated and characterized.
Michael Emerman - One of the best experts on this subject based on the ideXlab platform.
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the ability of Primate Lentiviruses to degrade the monocyte restriction factor samhd1 preceded the birth of the viral accessory protein vpx
Cell Host & Microbe, 2012Co-Authors: Oliver I Fregoso, Connor O Mccoy, Frederick A Matsen, Harmit S. Malik, Michael EmermanAbstract:The human SAMHD1 protein potently restricts lentiviral infection in dendritic cells and monocyte/macrophages but is antagonized by the Primate lentiviral protein Vpx, which targets SAMHD1 for degradation. However, only two of eight Primate Lentivirus lineages encode Vpx, whereas its paralog, Vpr, is conserved across all extant Primate Lentiviruses. We find that not only multiple Vpx but also some Vpr proteins are able to degrade SAMHD1, and such antagonism led to dramatic positive selection of SAMHD1 in the Primate subfamily Cercopithecinae. Residues that have evolved under positive selection precisely determine sensitivity to Vpx/Vpr degradation and alter binding specificity. By overlaying these functional analyses on a phylogenetic framework of Vpr and Vpx evolution, we can decipher the chronology of acquisition of SAMHD1-degrading abilities in Lentiviruses. We conclude that vpr neofunctionalized to degrade SAMHD1 even prior to the birth of a separate vpx gene, thereby initiating an evolutionary arms race with SAMHD1.
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Simian Immunodeficiency Virus SIVagm from African Green Monkeys Does Not Antagonize Endogenous Levels of African Green Monkey Tetherin/BST-2
Journal of virology, 2009Co-Authors: Efrem S. Lim, Michael EmermanAbstract:The Vpu accessory gene that originated in the Primate lentiviral lineage leading to human immunodeficiency virus type 1 is an antagonist of human tetherin/BST-2 restriction. Most other Primate Lentivirus lineages, including the lineage represented by simian immunodeficiency virus SIVagm from African green monkeys (AGMs), do not encode Vpu. While some Primate lineages encode gene products other than Vpu that overcome tetherin/BST-2, we find that SIVagm does not antagonize physiologically relevant levels of AGM tetherin/BST-2. AGM tetherin/BST-2 can be induced by low levels of type I interferon and can potently restrict two independent strains of SIVagm. Although SIVagm Nef had an effect at low levels of AGM tetherin/BST-2, simian immunodeficiency virus SIVmus Vpu, from a virus that infects the related monkey Cercopithecus cephus, is able to antagonize even at high levels of AGM tetherin/BST-2 restriction. We propose that since the replication of SIVagm does not induce interferon production in vivo, tetherin/BST-2 is not induced, and therefore, SIVagm does not need Vpu. This suggests that Primate Lentiviruses evolve tetherin antagonists such as Vpu or Nef only if they encounter tetherin during the typical course of natural infection.
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Conservation and host specificity of Vpr-mediated cell cycle arrest suggest a fundamental role in Primate Lentivirus evolution and biology.
Journal of virology, 1997Co-Authors: G L Stivahtis, Beatrice H. Hahn, Marcelo A. Soares, Marie A. Vodicka, Michael EmermanAbstract:The human immunodeficiency virus type 1 (HIV-1) Vpr protein prevents infected cells from passing through mitosis by arresting them in the G2 phase of the cell cycle. Vpr is conserved among all Primate Lentiviruses, suggesting an important role in the virus life cycle. Moreover, in this study we show that the ability to cause cell cycle arrest is also conserved in Vpr proteins from a wide variety of both tissue culture-passaged and uncultured human (HIV-1 and HIV-2), sooty mangabey (simian immunodeficiency virus SIV(SM)), African green monkey (SIV(AGM)), and Sykes' monkey (SIV(SYK)) isolates. However, this property is cell type specific and appears to depend on the particular Primate species from which the cells are derived. SIV(AGM) and SIV(SYK) Vpr proteins are capable of arresting African green monkey cells but are completely inactive in human cells. By contrast, HIV-1, HIV-2, and SIV(SM) Vpr proteins function in both simian and human cell types, although SIV(SM) Vpr functions more efficiently in simian cells than it does in human cells. Neither differential protein stability nor subcellular localization explains the species-specific activities of these proteins. These results thus suggest that Vpr exerts its G2 arrest function by interacting with cellular factors that have evolved differently among the various Primate species.
Philip R. Johnson - One of the best experts on this subject based on the ideXlab platform.
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A distinct African Lentivirus from Sykes' monkeys.
Journal of virology, 1993Co-Authors: Vanessa M. Hirsch, George Dapolito, Harold M. Mcclure, Patricia N. Fultz, Simoy Goldstein, P. Emau, Mohamed Isahakia, Rhoshel Lenroot, G. Myers, Philip R. JohnsonAbstract:Asymptomatic infection with simian immunodeficiency virus (SIV) has been demonstrated in African Sykes' monkeys (Cercopithecus mitis albogularis), and virus isolation confirmed infection with a novel SIV from Sykes' monkeys (SIVsyk). Macaques inoculated with SIVsyk became persistently infected but remained clinically healthy. We utilized polymerase chain reaction amplification to generate a full-length, infectious molecular clone of SIVsyk. The genome organization of SIVsyk is similar to that of the other Primate Lentiviruses, consisting of gag, pol, vif, vpr, tat, rev, env, and nef. A unique feature is the absence of the highly conserved NF-kappa B binding site in the long terminal repeat. SIVsyk is genetically equidistant from other Primate Lentiviruses. Thus, SIVsyk represents a new group that is distinct from the four previously recognized Primate Lentivirus groups: human immunodeficiency virus type 1 (HIV-1), SIV from sooty mangabeys (SIVsmm) and HIV-2, SIV from African green monkeys (SIVagm), and SIV from mandrills (SIVmnd). The genetic differences between SIVsyk and SIVagm, isolates derived from monkeys of the same genus, underscore the potential for other distinct SIVs which have yet to be isolated and characterized.
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SIV from stump-tailed macaques: molecular characterization of a highly transmissible Primate Lentivirus.
Virology, 1992Co-Authors: Francis J. Novembre, Vanessa M. Hirsch, Harold M. Mcclure, Patricia N. Fultz, Philip R. JohnsonAbstract:Over the past 6 years, simian immunodeficiency viruses (SIVs) have been isolated from four distinct species of macaques (Macaca mulatta, M. fascicularis, M. nemestrina, and M. arctoides) in captivity in the United States. However, the epidemiologic and genetic relationships among SIVs from the four species are not well understood. SIV from stump-tailed macaques (M. arctoides) (SIVstm) is unusual in that it has been associated with outbreaks of infection characterized by aggressive spread within stump-tailed macaque colonies at two separate Primate centers in the United States. To characterize SIVstm at the molecular level, we have derived six biologically active viral DNA clones by polymerase chain reaction amplification of genomic DNA from infected cells. Nucleotide sequence analyses of one clone (SIVstm/37.16) showed that SIVstm was indeed a member of the previously defined group of simian Lentiviruses that are closely related to the human immunodeficiency virus type 2 (HIV-2). However, our data indicate that SIVstm is equidistantly related to the other SIVs from macaques (SIVmac 251/142 and SIVmne) and SIV from African sooty mangabeys (SIVsmm). These findings suggest that SIV from captive macaques may have originated from several cross-species transmissions from imported sooty mangabeys and that additional spread has been fostered by the exchange of macaques among Primate centers.
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A highly divergent proviral DNA clone of SIV from a distinct species of African green monkey.
Virology, 1991Co-Authors: Anders Fomsgaard, Vanessa M. Hirsch, Jonathan S. Allan, Philip R. JohnsonAbstract:Simian immunodeficiency viruses from African green monkeys (SIVagm) are the most genetically heterogeneous type of non-human Primate Lentivirus. To further examine the extent of genetic divergence within the SIVagm type, we generated and sequenced a biologically active proviral DNA clone representing a Lentivirus isolated from a distinct African green monkey species (grivet). Overall, this clone (gri-1/lambda II) was highly divergent from previously characterized SIVagm clones. Specifically, the difference between gri-1/lambda II and other SIVagm clones approximated the difference between the caprine arthritis encephalitis virus and visna virus (two biologically and genetically distinct ruminant Lentiviruses). Our data suggest that Lentiviruses from African green monkeys may have evolved in concert with speciation of the genus and support the concept that SIVagm may be the oldest Primate Lentivirus type in existence.
Martine Peeters - One of the best experts on this subject based on the ideXlab platform.
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the presence of a vpu gene and the lack of nef mediated downmodulation of t cell receptor cd3 are not always linked in Primate Lentiviruses
Journal of Virology, 2011Co-Authors: Jan Schmokel, Frederic Bibolletruche, Martine Peeters, Daniel Sauter, Michael Schindler, Fabian H Leendertz, Elizabeth Bailes, M C Dazza, Sentob Saragosti, Beatrice H. HahnAbstract:Nef is an accessory protein critical for the ability of human and simian immunodeficiency viruses (HIV and SIV) to replicate efficiently in their respective hosts. Previous analyses of members of 15 different Primate Lentivirus lineages revealed a link between Nef function and the presence of a vpu gene. In particular, Nef proteins of all vpu-containing viruses had lost their ability to downmodulate the T cell (TCR-CD3) receptor. Here we examined Nef proteins from eight additional SIV lineages, including SIVgor, SIVwrc, SIVolc, SIVgri, SIVdrl, SIVlho, SIVden, and SIVasc, from western lowland gorillas, western red colobus monkeys, olive colobus monkeys, grivet monkeys, drills, L'Hoest's monkeys, Dent's mona monkeys, and red-tailed monkeys, respectively. We found that except for the nef gene of SIVdrl, all of them were efficiently expressed and modulated CD4, major histocompatibility complex class I (MHC-I), CD28, CXCR4, and Ii cell surface expression and/or enhanced viral infectivity and replication. Furthermore, the Nef proteins of SIVgri, SIVlho, SIVwrc, SIVolc, and SIVgor antagonized tetherin. As expected, the Nef protein of SIVgor, which carries vpu, failed to downmodulate CD3, whereas those of SIVwrc, SIVgri, SIVlho, and SIVasc, which lack vpu, were capable of performing this function. Surprisingly, however, the Nef protein of the vpu-containing SIVden strain retained the ability to downmodulate TCR-CD3, whereas that of SIVolc, which does not contain vpu, was unable to perform this function. Although the SIVden Vpu is about 20 amino acids shorter than other Vpu proteins, it degrades CD4 and antagonizes tetherin. Our data show that there are exceptions to the link between the presence of a vpu gene and nef alleles deficient in CD3 modulation, indicating that host properties also affect the selective pressure for Nef-mediated disruption of TCR-CD3 signaling. Our results are also further evidence that tetherin antagonism is a common function of Primate Lentivirus Nef proteins and that the resistance of human tetherin to Nef represents a relevant barrier to cross-species transmission of SIVs to humans.
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Identification of a New Simian Immunodeficiency Virus Lineage with a vpu Gene Present among Different Cercopithecus Monkeys (C. mona, C. cephus, and C. nictitans) from Cameroon
Journal of virology, 2003Co-Authors: Valerie Courgnaud, Xavier Pourrut, Eric Delaporte, Bernadette Abela, Eitel Mpoudi-ngole, Severin Loul, Martine PeetersAbstract:During a large serosurvey of wild-caught Primates from Cameroon, we found 2 mona monkeys (Cercopithecus mona) out of 8 and 47 mustached monkeys (Cercopithecus cephus) out of 302 with human immunodeficiency virus (HIV)-simian immunodeficiency virus (SIV) cross-reactive antibodies. In this report, we describe the full-length genome sequences of two novel SIVs, designated SIVmon-99CMCML1 and SIVmus-01CM1085, isolated from one mona (CML1) and one mustached (1085) monkey, respectively. Interestingly, these viruses displayed the same genetic organization (i.e., presence of a vpu homologue) as members of the SIVcpz-HIV type 1 lineage and SIVgsn isolated from greater spot-nosed monkeys (Cercopithecus nictitans). Phylogenetic analyses of SIVmon and SIVmus revealed that these viruses were genetically distinct from other known Primate Lentiviruses but were more closely related to SIVgsn all across their genomes, thus forming a monophyletic lineage within the Primate Lentivirus family, which we designated the SIVgsn lineage. Interestingly, mona, mustached, and greater spot-nosed monkeys are phylogenetically related species belonging to three different groups of the genus Cercopithecus, the C. mona, C. cephus, and Cercopithecus mitis groups, respectively. The presence of new viruses closely related to SIVgsn in two other species reinforces the hypothesis that a recombination event between ancestral SIVs from the family Cercopithecinae is the origin of the present SIVcpz that is widespread among the chimpanzee population.
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Partial molecular characterization of two simian immunodeficiency viruses (SIV) from African colobids: SIVwrc from Western red colobus (Piliocolobus badius) and SIVolc from olive colobus (Procolobus verus).
Journal of virology, 2003Co-Authors: Valerie Courgnaud, Eric Delaporte, Pierre Formenty, Chantal Akoua-koffi, Ronald Noë, Christophe Boesch, Martine PeetersAbstract:In order to study Primate Lentivirus evolution in the Colobinae subfamily, in which only one simian immunodeficiency virus (SIV) has been described to date, we screened additional species from the three different genera of African colobus monkeys for SIV infection. Blood was obtained from 13 West African colobids, and HIV cross-reactive antibodies were observed in 5 of 10 Piliocolobus badius, 1 of 2 Procolobus verus, and 0 of 1 Colobus polykomos specimens. Phylogenetic analyses of partial pol sequences revealed that the new SIVs were more closely related to each other than to the other SIVs and especially did not cluster with the previously described SIVcol from Colobus guereza. This study presents evidence that the three genera of African colobus monkeys are naturally infected with an SIV and indicates also that there was no coevolution between virus and hosts at the level of the Colobinae subfamily.
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characterization of a novel simian immunodeficiency virus from guereza colobus monkeys colobus guereza in cameroon a new lineage in the nonhuman Primate Lentivirus family
Journal of Virology, 2001Co-Authors: Valerie Courgnaud, Xavier Pourrut, Frederic Bibolletruche, Eitel Mpoudingole, Anke Bourgeois, Eric Delaporte, Martine PeetersAbstract:Exploration of the diversity among Primate Lentiviruses is necessary to elucidate the origins and evolution of immunodeficiency viruses. During a serological survey in Cameroon, we screened 25 wild-born guereza colobus monkeys (Colobus guereza) and identified 7 with HIV/SIV cross-reactive antibodies. In this study, we describe a novel Lentivirus, named SIVcol, prevalent in guereza colobus monkeys. Genetic analysis revealed that SIVcol was very distinct from all other known SIV/HIV isolates, with average amino acid identities of 40% for Gag, 50% for Pol, 28% for Env, and around 25% for proteins encoded by five other genes. Phylogenetic analyses confirmed that SIVcol is genetically distinct from other previously characterized Primate Lentiviruses and clusters independently, forming a novel lineage, the sixth in the current classification. Cercopithecidae monkeys (Old World monkeys) are subdivided into two subfamilies, the Colobinae and the Cercopithecinae, and, so far, all Cercopithecidae monkeys from which Lentiviruses have been isolated belong to the Cercopithecinae subfamily. Therefore, SIVcol from guereza colobus monkeys (C. guereza) is the first Primate Lentivirus identified in the Colobinae subfamily and the divergence of SIVcol may reflect divergence of the host lineage.
Beatrice H. Hahn - One of the best experts on this subject based on the ideXlab platform.
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the presence of a vpu gene and the lack of nef mediated downmodulation of t cell receptor cd3 are not always linked in Primate Lentiviruses
Journal of Virology, 2011Co-Authors: Jan Schmokel, Frederic Bibolletruche, Martine Peeters, Daniel Sauter, Michael Schindler, Fabian H Leendertz, Elizabeth Bailes, M C Dazza, Sentob Saragosti, Beatrice H. HahnAbstract:Nef is an accessory protein critical for the ability of human and simian immunodeficiency viruses (HIV and SIV) to replicate efficiently in their respective hosts. Previous analyses of members of 15 different Primate Lentivirus lineages revealed a link between Nef function and the presence of a vpu gene. In particular, Nef proteins of all vpu-containing viruses had lost their ability to downmodulate the T cell (TCR-CD3) receptor. Here we examined Nef proteins from eight additional SIV lineages, including SIVgor, SIVwrc, SIVolc, SIVgri, SIVdrl, SIVlho, SIVden, and SIVasc, from western lowland gorillas, western red colobus monkeys, olive colobus monkeys, grivet monkeys, drills, L'Hoest's monkeys, Dent's mona monkeys, and red-tailed monkeys, respectively. We found that except for the nef gene of SIVdrl, all of them were efficiently expressed and modulated CD4, major histocompatibility complex class I (MHC-I), CD28, CXCR4, and Ii cell surface expression and/or enhanced viral infectivity and replication. Furthermore, the Nef proteins of SIVgri, SIVlho, SIVwrc, SIVolc, and SIVgor antagonized tetherin. As expected, the Nef protein of SIVgor, which carries vpu, failed to downmodulate CD3, whereas those of SIVwrc, SIVgri, SIVlho, and SIVasc, which lack vpu, were capable of performing this function. Surprisingly, however, the Nef protein of the vpu-containing SIVden strain retained the ability to downmodulate TCR-CD3, whereas that of SIVolc, which does not contain vpu, was unable to perform this function. Although the SIVden Vpu is about 20 amino acids shorter than other Vpu proteins, it degrades CD4 and antagonizes tetherin. Our data show that there are exceptions to the link between the presence of a vpu gene and nef alleles deficient in CD3 modulation, indicating that host properties also affect the selective pressure for Nef-mediated disruption of TCR-CD3 signaling. Our results are also further evidence that tetherin antagonism is a common function of Primate Lentivirus Nef proteins and that the resistance of human tetherin to Nef represents a relevant barrier to cross-species transmission of SIVs to humans.
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Primate Lentivirus Capsid Sensitivity to TRIM5 Proteins
Journal of Virology, 2008Co-Authors: Zerina Kratovac, Cesar A. Virgen, Frederic Bibollet-ruche, Beatrice H. Hahn, Theodora HatziioannouAbstract:Mammalian cells express several factors that inhibit lentiviral infection and that have been under strong selective pressure. One of these factors, TRIM5, targets the capsid protein of incoming retrovirus particles and inhibits subsequent steps of the replication cycle. By substituting human immunodeficiency virus type 1 capsid, we were able to show that a set of divergent Primate Lentivirus capsids was generally not susceptible to restriction by TRIM5 proteins from higher Primates. TRIM5α proteins from other Primates exhibited distinct restriction specificities for Primate Lentivirus capsids. Finally, we identified novel Primate lentiviral capsids that are targeted by TRIMCyp proteins.
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Origins and evolution of AIDS viruses: estimating the time-scale.
Biochemical Society transactions, 2000Co-Authors: Paul M. Sharp, Vanessa M. Hirsch, Feng Gao, Elizabeth Bailes, Brigitte E. Beer, Beatrice H. HahnAbstract:The Primate Lentiviruses comprise SIV strains from various host species, as well as two viruses, HIV-1 and HIV-2, that cause AIDS in humans. The origins of HIV-1 and HIV-2 have been traced to cross-species transmissions from chimpanzees and sooty mangabey monkeys respectively. Two approaches have been taken to estimate the time-scale of the evolution of these viruses. Certain groups of SIV strains appear to have evolved in a host-dependent manner, implying a time-scale of many thousands or even millions of years. In stark contrast, molecular clock calculations have previously been used to estimate a time-scale of only tens or hundreds of years. Those calculations largely ignored heterogeneity of evolutionary rates across different sites within sequences. In fact, the distribution of rates at different sites seems extremely skewed in HIV-1, and so the time-depth of the Primate Lentivirus evolutionary tree may have been underestimated by at least a factor of ten. However, these date estimates still seem to be far too recent to be consistent with host-dependent evolution.
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Conservation and host specificity of Vpr-mediated cell cycle arrest suggest a fundamental role in Primate Lentivirus evolution and biology.
Journal of virology, 1997Co-Authors: G L Stivahtis, Beatrice H. Hahn, Marcelo A. Soares, Marie A. Vodicka, Michael EmermanAbstract:The human immunodeficiency virus type 1 (HIV-1) Vpr protein prevents infected cells from passing through mitosis by arresting them in the G2 phase of the cell cycle. Vpr is conserved among all Primate Lentiviruses, suggesting an important role in the virus life cycle. Moreover, in this study we show that the ability to cause cell cycle arrest is also conserved in Vpr proteins from a wide variety of both tissue culture-passaged and uncultured human (HIV-1 and HIV-2), sooty mangabey (simian immunodeficiency virus SIV(SM)), African green monkey (SIV(AGM)), and Sykes' monkey (SIV(SYK)) isolates. However, this property is cell type specific and appears to depend on the particular Primate species from which the cells are derived. SIV(AGM) and SIV(SYK) Vpr proteins are capable of arresting African green monkey cells but are completely inactive in human cells. By contrast, HIV-1, HIV-2, and SIV(SM) Vpr proteins function in both simian and human cell types, although SIV(SM) Vpr functions more efficiently in simian cells than it does in human cells. Neither differential protein stability nor subcellular localization explains the species-specific activities of these proteins. These results thus suggest that Vpr exerts its G2 arrest function by interacting with cellular factors that have evolved differently among the various Primate species.