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At least 19 recordsLinked to original sources
PubMed1993

Compatibility of Tat and Rev transactivators in the primate lentiviruses.

Primate immunodeficiency viruses carry a unique set of transacting regulator genes, which are essential for viral replication. The exchangeability of these Tat and Rev transactivators derived from viruses of the four major subgroups identified to date was assessed in transient transfection and infection assay systems. The human immunodeficiency virus type 1 (HIV-1), a major causative virus of human AIDS, efficiently activated the other viruses. In contrast, the tat and rev gene products of HIV-2, SIVAGM (virus of the African green monkey), and SIVMND (virus of the mandrill) did not fully transactivate the HIV-1. In particular, the rev of HIV-1 was not substantially replaced by those of the other viruses. The result that HIV-1 is distinct from the other immunodeficiency viruses with respect to the compatibility of two transactivators gives a firm functional basis for the unique phylogenetic position of HIV-1.

Amino Acid Sequence↗
PubMedDate not supplied

The Nef protein of primate lentiviruses.

The Nef protein of primate lentiviruses acts as an important virulence factor in vivo both in monkeys and in humans. Among a human cohort of long-term non-progressors, several Nef defective HIV1 viruses have been isolated, indicating that Nef may accelerate HIV progression and disease in humans. Additionally, a Nef-deleted SIV virus has low titres in rhesus monkeys and the animals develop AIDS at a much slower rate. In vitro, Nef can exert at least three kinds of effects: it downregulates CD4 and MHC class I, it stimulates virion infectivity and it alters signal transduction pathways. To accomplish this, Nef interacts with a series of cellular partners including CD4, components of the adaptor complexes AP-1 and AP-2, and several protein kinases, Nef often functioning as a connector between targets and effectors. The high degree of understanding of at least some aspects of Nef action, as well as the importance of this viral gene product for disease induction, identify Nef as a valuable target for the development of novel antiviral therapies. Moreover, the possibility of developing vaccines using attenuated viruses with deletions in nef and other crucial genes raises the possibility that the AIDS epidemic might one day be restrained.

Animals↗
PubMed2001

Characterization of a novel simian immunodeficiency virus from guereza colobus monkeys (Colobus guereza) in Cameroon: a new lineage in the nonhuman primate lentivirus family.

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.

Amino Acid Sequence↗
PubMed2002

Preferential host switching by primate lentiviruses can account for phylogenetic similarity with the primate phylogeny.

Primate lentiviruses (PLV) from closely related primate species have been observed to be more closely related to each other than to PLV from more distantly related primate species. The current explanation for this observation is the codivergence hypothesis; that is, the divergence of a virus lineage results from the divergence of the host lineage. We show that, alternatively, frequent cross-species transmission of PLV, coupled with a tendency for more closely related primate species to exchange viruses "successfully," can result in apparent codivergence. This host-switching hypothesis reconciles several puzzling observations related to the evolution of PLV.

Animals↗
PubMed2006

High frequency of genetic recombination is a common feature of primate lentivirus replication.

Recent studies indicate that human immunodeficiency virus type 1 (HIV-1) recombines at exceedingly high rates, approximately 1 order of magnitude more frequently than simple gammaretroviruses such as murine leukemia virus and spleen necrosis virus. We hypothesize that this high frequency of genetic recombination is a common feature of primate lentiviruses. Alternatively, it is possible that HIV-1 is unique among primate lentiviruses in possessing high recombination rates. Among other primate lentiviruses, only the molecular mechanisms of HIV-2 replication have been extensively studied. There are reported differences between the replication mechanisms of HIV-1 and those of HIV-2, such as preferences for RNA packaging in cis and properties of reverse transcriptase and RNase H activities. These biological disparities could lead to differences in recombination rates between the two viruses. Currently, HIV-1 is the only primate lentivirus in which recombination rates have been measured. To test our hypothesis, we established recombination systems to measure the recombination rates of two other primate lentiviruses, HIV-2 and simian immunodeficiency virus from African green monkeys (SIVagm), in one round of viral replication. We determined that, for markers separated by 588, 288, and 90 bp, HIV-2 recombined at rates of 7.4%, 5.5%, and 2.4%, respectively, whereas SIVagm recombined at rates of 7.8%, 5.6%, and 2.7%, respectively. These high recombination rates are within the same range as the previously measured HIV-1 recombination rates. Taken together, our results indicate that HIV-1, HIV-2, and SIVagm all possess high recombination frequencies; hence, the high recombination potential is most likely a common feature of primate lentivirus replication.

Cell Line↗
PubMed1993

Rates of amino acid change in the envelope protein correlate with pathogenicity of primate lentiviruses.

A spectrum of pathogenicity has been observed for primate lentiviruses in their natural hosts. For example, human immunodeficiency virus type 1 (HIV-1) is a potent etiologic agent for AIDS in man, whereas there is no evidence to date which indicates that simian immunodeficiency virus from African green monkeys (SIVAGM) causes immunodeficiency in AGM. We measured the relative rates of amino acid change, as the ratio of the number of nonsynonymous to synonymous (silent) nucleotide substitutions, for six primate lentiviruses evolving in their respective hosts. These rates for the external envelope glycoprotein (gp120) and gag coding sequences are 2-3 times higher for pathogenic HIV-1 and SIVmac (macaque) than for minimally pathogenic SIVAGM and SIVsmm (sooty mangabey), and intermediate for HIV-2. We speculate that the increased rates of nonsynonymous changes in gp120 and gag coding sequences are due to viral escape from immune surveillance and are indicative of higher immunogenicity of these proteins in their hosts. Based on these results and available experimental data, we conclude that there is a positive correlation between lentiviral pathogenicity and immunogenicity of the Env and Gag proteins in a given host. This hypothesis is consistent with recent data suggesting that immune system activation or autoimmunity induced by viral antigens may be important in the pathogenesis of AIDS.

Amino Acids↗
PubMed1992

A comparison of regulatory features in primate lentiviruses.

Historically, research into the regulation of gene expression in primate lentiviruses has focused on human immunodeficiency virus type 1 (HIV-1), the primary cause of acquired immunodeficiency syndrome (AIDS) in humans. The increasing emergence of HIV-2 as a human pathogen, and the importance of the various simian immunodeficiency viruses (SIV) as models for the treatment and prevention of HIV-1-induced disease, suggest that an understanding of gene regulation in these related viruses will become increasingly important. Here, the present state of knowledge in this latter field is reviewed. In general, while the data support the hypothesis that viral gene expression is regulated by very similar mechanisms in all primate lentiviruses, it also is clear that differences in detail do exist. These differences may influence the pathogenic potential of the different strains of primate lentiviruses and must be considered in evaluating SIV as an appropriate in vivo model for HIV-1.

Amino Acid Sequence↗
PubMed1995

Phylogeny and natural history of the primate lentiviruses, SIV and HIV.

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.

Africa↗
PubMed1994

Antigenic variation of primate lentiviruses in humans and experimentally infected macaques.

Neutralizing antibodies in primate lentivirus infections closely parallel the pathogenic process. Fast progression to disease is concomitant with lack of neutralizing antibodies to autologous virus. Slow or no progression to disease is linked with production of neutralizing antibodies to autologous virus. Moreover, there is evidence from the monkey model that the extent to which neutralizing antibodies cross-react may also be linked with the pathogenic process. Accordingly, slow progression to disease is associated with the capacity to neutralize several isolates and, conversely, fast progressors neutralize single autologous isolates, if any at all. In humans, transmission of HIV-1 from mother to child occurs more frequently in absence of autologous and/or heterologous neutralizing antibodies to primary isolates. Thus there is evidence that virus neutralization-perhaps in concert with the biological properties of the virus-is an important factor in primate lentivirus pathogenesis and transmission. Open questions are i) the extent of heterologous neutralization in slow or nonprogressor HIV-1- and HIV-2-infected individuals, ii) role of neutralizing antibodies in sexual transmission, and iii) what governs the specificity, broad or narrow, of the neutralizing antibody response in different hosts. If we can answer these questions we may be able to design preventive measures against HIV infection and/or disease. Studies on the interaction of virus and immune system in the infected host may therefore not only teach us about the pathogenetic process, but also help in developing an HIV vaccine.

Animals↗
PubMed1992

Evolution of the primate lentiviruses: evidence from vpx and vpr.

The genomes of the four primate lentiviral groups are complex and contain several regulatory or accessory genes. Two of these genes, vpr and vpx, are found in various combinations within the four groups and encode proteins whose functions have yet to be elucidated. Comparison of the encoded protein sequences suggests that the vpx gene within the HIV-2 group arose by the duplication of an ancestral vpr gene within this group. Evolutionary distance analysis showed that both genes were well conserved when compared with viral regulatory genes, and indicated that the duplication occurred at approximately the same time as the HIV-2 group and the other primate lentivirus groups diverged from a common ancestor. Furthermore, although the SIVagm vpx proteins are homologous to the HIV-2 group vpx proteins, there are insufficient grounds from sequence analysis for classifying them as vpx proteins. Because of their similarity to the vpr proteins of other groups, we suggest reclassifying the SIVagm vpx gene as a vpr gene. This creates a simpler and more uniform picture of the genomic organization of the primate lentiviruses and allows the genomic organization of their common precursor to be defined; it probably contained five accessory genes: tat, rev, vif, nef and vpr.

Amino Acid Sequence↗
PubMed1996

Broad cross-neutralizing activity in serum is associated with slow progression and low risk of transmission in primate lentivirus infections.

Sera from human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2)-infected humans were tested with autologous (from the same individual) and heterologous (from other individuals) virus isolates in a neutralization assay. Similarly, sera from experimentally simian immunodeficiency virus (SIVsm from sooty mangabey) or HIV-2SBL6669-infected cynomolgus macaques were tested for neutralizing activity against autologous and heterologous reisolates. In the neutralization assay, the virus dose ranged between 10-75 50% infectious dose (ID50), sera were used in five 2- or 4-fold dilutions, beginning with 1:20, and human peripheral blood mononuclear cells (PBMCs) served as target cells. The readout of the 7-day assay was a HIV-1 or HIV-2 antigen enzyme-linked immunosorbent assay (ELISA). Our results show that SIVsm-inoculated monkeys who develop early immunodeficiency lack serum neutralizing activity or develop a neutralizing antibody response with narrow specificity. Long survival is associated with the ability to neutralize several autologous and heterologous SIVsm reisolates. Infection of macaques with HIV-2SBL6669 did not cause disease within the 5 years observation time and elicited a broadly cross-reactive neutralizing antibody response, including neutralization of other, independently obtained, HIV-2 isolates. In HIV-1-infected humans, neutralizing antibodies can only be detected in up to 50% of cases. Neutralizing activity, whenever present, may show a broad specificity, that is, neutralization may occur across genetic subtypes. Presence of broadly cross-reactive neutralizing antibodies is associated with a lower risk of HIV-1 (subtype B) transmission both from mother to child and sexually from male to female. Unlike HIV-1 infection, serum neutralizing activity is regularly present in HIV-2 infection. In view of the differences between HIV-1 and HIV-2 pathogenesis, we suggest that an effective neutralizing antibody response may contribute to a delay in disease progression and to a decrease in risk of transmission.

Animals↗
PubMed2002

Quantitation of simian cytokine and beta-chemokine mRNAs, using real-time reverse transcriptase-polymerase chain reaction: variations in expression during chronic primate lentivirus infection.

Cytokines and beta-chemokines are important mediators of the immune system and are expressed in many infectious diseases. To study cytokine and beta-chemokine profiles during pathogenesis of lentiviral infection and progression to AIDS in rhesus macaques, we established new quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assays based on TaqMan chemistry. Using synthetic RNA standards, we quantified mRNAs of IL-2, IL-4, IL-6, IL-10, IL-12 p40, interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), RANTES, macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta in unstimulated peripheral blood mononuclear cells (PBMCs) and lymph nodes from macaques chronically infected with SIV or SHIV. Viremic monkeys with decreased CD4(+) T cell counts (<500 cells/microl) had significantly higher IL-10 mRNA expression than uninfected controls, which parallels the findings in HIV-1-infected humans. In addition, MIP-1 alpha, MIP-1 beta, and RANTES mRNA expression increased in viremic monkeys with decreased CD4(+) T cell counts; gene expression was inversely correlated with CD4(+) T cell counts, but not viral load. The newly established quantitative real-time RT-PCR assays will allow the determination of cytokine and beta-chemokine patterns in rhesus macaques in studies of microbial pathogenesis or vaccine development.

Animals↗
PubMed2005

[Analysis on primate lentivirus genome dimerization in virion].

The genomic RNA of retrovirus, including the primate lentivirus such as HIV, always form dimers in matured virions. It is likely that the presence of two genomes in one virion is advantageous for survival, providing an extra template that can be used when one RNA molecule is damaged, and/or giving genetic variety to their progeny. However, these ideas might not fully explain why the virion have to carry multiple identical RNAs in spite of the severe limitation of the space. We developed and utilized a novel system to investigate viral RNA dimerization in virion clearly and simply without affecting RNA packaging. The results of precise mapping of dimerization functional region strongly suggested that the RNA dimerization is one of the essential steps of RNA packaging.

Dimerization↗
PubMed2004

Cell-free systems for capsid assembly of primate lentiviruses from three different lineages.

We recently demonstrated that capsids from three main primate lentiviral lineages appear to form via a pathway of assembly intermediates in primate cells. Retroviral capsid assembly intermediates were initially identified and characterized using a cell-free system for assembly of immature HIV-1 capsids. Because cell-free capsid assembly systems are useful tools, we are interested in developing such systems for other primate lentiviruses besides HIV-1. Here we extend previous cell-free studies by showing that Gag proteins of HIV-2, from a second primate lentiviral lineage, progress from early intermediates to late intermediates and completed capsids over time. Additionally, we demonstrate that Gag proteins of SIVagm, from a third primate lentiviral lineage, associate with the cellular factor HP68 and complete assembly in this system. Therefore, cell-free systems reproduce assembly of Gag from three main primate lentiviral lineages, and can be used to compare mechanistic features of capsid assembly of genetically divergent primate lentiviruses.

Animals↗
PubMedDate not supplied

Transactivation is a conserved function among primate lentivirus Vpr proteins but is not shared by Vpx.

OBJECTIVE: To investigate the transactivating activity of Vpr proteins from human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) and simian immunodeficiency viruses (SIVs) on various primate lentivirus long terminal repeats (LTRs), and to determine whether the Vpx proteins shared by HIV-2 and SIV are able to transactivate any HIV or SIV promoter. STUDY DESIGN/METHODS: The vpr and vpx genes of the HIVs and SIVs encode virion-associated proteins, which are implicated in viral replication and pathogenesis. HIV-1 Vpr is involved in the transport of the preintegration complex (PIC) to the nucleus, transactivates the viral LTR, and induces cell cycle arrest. HIV-2 and SIV Vpx proteins share amino acid sequence similarities with Vpr and are involved in PIC translocation into the nucleus but are unable to induce cell cycle arrest. We cloned and expressed the vpr and vpx genes from several primate lentiviruses and tested their transactivating ability on HIV-1, HIV-2, SIVmac and SIVagm LTRs cloned upstream of the CAT reporter gene. RESULTS: All Vpr tested had a transactivating effect on several viral LTRs; however, none of the Vpx proteins showed a detectable transactivating effect. CONCLUSIONS: These results indicate that the transactivating properties of Vpr proteins were conserved throughout evolution in primate lentiviruses, which suggests that they have an important role in virus replication.

Amino Acid Sequence↗