Prehistory of HIV-1

Nature (Impact Factor: 41.46). 11/2008; 455(7213):605-6. DOI: 10.1038/455605a
Source: PubMed


The origin of the current AIDS pandemic has been a subject of great interest and speculation. Viral archaeology sheds light on the geography and timescale of the early diversification of HIV-1 in humans.

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    • "The biological significance of the breadth of protection by FIV Vif but also the breadth of feA3 binding by FFV Bet is currently not understood but may be studied in transgenic cats similar to those that have been recently established (Wongsrikeao et al., 2011). The broad protection against restriction may reflect a much longer host-virus co-evolution of cats with both feline retroviruses versus the situation in human where HIV was only recently acquired by men while repeated zoonotic transmissions of simian FVs to human beings have not resulted in the stable establishment of FVs in the human population (Heneine et al., 2003; Pecon-Slattery et al., 2008; Sharp and Hahn, 2008; Switzer et al., 2005). Since the steady state levels of feA3 proteins are not affected by Bet, protection against restriction is most probably mediated by Bet-feA3 complex formation as discussed previously (Löchelt et al., "
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    ABSTRACT: Defined host-encoded feline APOBEC3 (feA3) cytidine deaminases efficiently restrict the replication and spread of exogenous retroviruses like Feline Immunodeficiency Virus (FIV) and Feline Foamy Virus (FFV) which developed different feA3 counter-acting strategies. Here we characterize the molecular interaction of FFV proteins with the diverse feA3 proteins. The FFV accessory protein Bet is the virus-encoded defense factor which is shown here to bind all feA3 proteins independent of whether they restrict FFV, a feature shared with FIV Vif that induces degradation of all feA3s including those that do not inactivate FIV. In contrast, only some feA3 proteins bind to FFV Gag, a pattern that in part reflects the restriction pattern detected. Additionally, one-domain feA3 proteins can homo- and hetero-dimerize in vitro, but a trans-dominant phenotype of any of the low-activity feA3 forms on FFV restriction by one of the highly-active feA3Z2 proteins was not detectable.
    Virology 03/2012; 424(2):138-46. DOI:10.1016/j.virol.2011.12.017 · 3.32 Impact Factor
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    • "Leopoldville was the largest city in the region at that time and thus a likely destination for a newly emerging infection. Moreover, rivers, which served as major routes of travel and commerce at the time, would have provided a link between the chimpanzee reservoir of HIV-1 group M in southeastern Cameroon and Leopoldville on the banks of the Congo (Sharp and Hahn 2008). Thus, all current evidence points to Leopoldville/Kinshasa as the cradle of the AIDS pandemic. "
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    ABSTRACT: Acquired immunodeficiency syndrome (AIDS) of humans is caused by two lentiviruses, human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2). Here, we describe the origins and evolution of these viruses, and the circumstances that led to the AIDS pandemic. Both HIVs are the result of multiple cross-species transmissions of simian immunodeficiency viruses (SIVs) naturally infecting African primates. Most of these transfers resulted in viruses that spread in humans to only a limited extent. However, one transmission event, involving SIVcpz from chimpanzees in southeastern Cameroon, gave rise to HIV-1 group M-the principal cause of the AIDS pandemic. We discuss how host restriction factors have shaped the emergence of new SIV zoonoses by imposing adaptive hurdles to cross-species transmission and/or secondary spread. We also show that AIDS has likely afflicted chimpanzees long before the emergence of HIV. Tracing the genetic changes that occurred as SIVs crossed from monkeys to apes and from apes to humans provides a new framework to examine the requirements of successful host switches and to gauge future zoonotic risk.
    Cold Spring Harbor Perspectives in Medicine 09/2011; 1(1):a006841. DOI:10.1101/cshperspect.a006841 · 9.47 Impact Factor
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    • "HIV-1 viruses evolved from a common ancestor circulating at the beginning of the twentieth century [44] that was acquired by humans through cross-species transmissions followed by a split into HIV-1 M group subtypes as a result of founder events [49,50]. We estimated the date of HIV-1 subtype C diversification around 1950 (1928–1962). "
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    ABSTRACT: The diversity of HIV-1 and its propensity to generate escape mutants present fundamental challenges to control efforts, including HIV vaccine design. Intra-host diversification of HIV is determined by immune responses elicited by an HIV-infected individual over the course of the infection. Complex and dynamic patterns of transmission of HIV lead to an even more complex population viral diversity over time, thus presenting enormous challenges to vaccine development. To address inter-patient viral evolution over time, a set of 653 unique HIV-1 subtype C gag sequences were retrieved from the LANL HIV Database, grouped by sampling year as <2000, 2000, 2001-2002, 2003, and 2004-2006, and analyzed for the site-specific frequency of translated amino acid residues. Phylogenetic analysis revealed that a total of 289 out of 653 (44.3%) analyzed sequences were found within 16 clusters defined by aLRT of more than 0.90. Median (IQR) inter-sample diversity of analyzed gag sequences was 8.7% (7.7%; 9.8%). Despite the heterogeneous origins of analyzed sequences, the gamut and frequency of amino acid residues in wild-type Gag were remarkably stable over the last decade of the HIV-1 subtype C epidemic. The vast majority of amino acid residues demonstrated minor frequency fluctuation over time, consistent with the conservative nature of the HIV-1 Gag protein. Only 4.0% (20 out of 500; HXB2 numbering) amino acid residues across Gag displayed both statistically significant (p<0.05 by both a trend test and heterogeneity test) changes in amino acid frequency over time as well as a range of at least 10% in the frequency of the major amino acid. A total of 59.2% of amino acid residues with changing frequency of 10%+ were found within previously identified CTL epitopes. The time of the most recent common ancestor of the HIV-1 subtype C was dated to around 1950 (95% HPD from 1928 to 1962). This study provides evidence for the overall stability of HIV-1 subtype C Gag among viruses circulating in the epidemic over the last decade. However selected sites across HIV-1C Gag with changing amino acid frequency are likely to be under selection pressure at the population level.
    Viruses 01/2010; 2(1):33-54. DOI:10.3390/v2010033 · 3.35 Impact Factor
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