Origins of HIV and the AIDS pandemic

Institute of Evolutionary Biology and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
Cold Spring Harbor Perspectives in Medicine (Impact Factor: 7.56). 09/2011; 1(1):a006841. DOI: 10.1101/cshperspect.a006841
Source: PubMed

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.

Download full-text


Available from: Paul M Sharp, Jul 30, 2014
1 Follower
  • Source
    • "In sub-Saharan Africa, bushmeat hunting and butchering is widely considered to be the primary risk factor for human–wildlife contact and zoonotic viral transmission (Peeters et al. 2002; Wolfe et al. 2004a; Locatelli and Peeters 2012). Human immunodeficiency virus, the cause of AIDS, evolved from related viruses of nonhuman primates (''primates,'' hereafter) that entered human populations through multiple zoonotic events as a result of bushmeat hunting and butchering in West and Central Africa (Sharp and Hahn 2011; Locatelli and Peeters 2012). In addition, other retroviruses have crossed into persons with primate contact in Africa, including simian foamy virus (SFV) and simian T cell lymphotropic virus (Wolfe and Switzer 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Zoonotic pathogens cause an estimated 70% of emerging and re-emerging infectious diseases in humans. In sub-Saharan Africa, bushmeat hunting and butchering is considered the primary risk factor for human-wildlife contact and zoonotic disease transmission, particularly for the transmission of simian retroviruses. However, hunting is only one of many activities in sub-Saharan Africa that bring people and wildlife into contact. Here, we examine human-animal interaction in western Uganda, identifying patterns of injuries from animals and contact with nonhuman primates. Additionally, we identify individual-level risk factors associated with contact. Nearly 20% (246/1,240) of participants reported either being injured by an animal or having contact with a primate over their lifetimes. The majority (51.7%) of injuries were dog bites that healed with no long-term medical consequences. The majority (76.8%) of 125 total primate contacts involved touching a carcass; however, butchering (20%), hunting (10%), and touching a live primate (10%) were also reported. Red colobus (Piliocolobus rufomitratus tephrosceles) accounted for most primate contact events. Multivariate logistic regression indicated that men who live adjacent to forest fragments are at elevated risk of animal contact and specifically primate contact. Our results provide a useful comparison to West and Central Africa where "bushmeat hunting" is the predominant paradigm for human-wildlife contact and zoonotic disease transmission.
    EcoHealth 05/2014; 11(4). DOI:10.1007/s10393-014-0942-y · 2.27 Impact Factor
  • Source
    • "Simian immunodeficiency virus (SIV) constitutes a class of lentiviruses detected in over 40 species of nonhuman primates (Chahroudi et al., 2012). SIVcpz, the SIV strain that infects chimpanzees, was transmitted to humans in the early 20 th century (Korber et al., 2000), resulting in the global HIV-1 epidemic (Sharp and Hahn, 2011). In contrast to most SIVs, both SIVcpz and HIV type 1 (HIV-1) are pathogenic and can cause acquired immunodeficiency syndrome (AIDS) through the progressive depletion of host CD4 + T cells (Keele et al., 2009; Pantaleo et al., 1993). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Simian immunodeficiency virus of chimpanzees (SIVcpz) is the ancestor of human immunodeficiency virus type 1 (HIV-1), the etiologic agent of acquired immunodeficiency syndrome (AIDS) in humans. Like HIV-1-infected humans, SIVcpz-infected chimpanzees can develop AIDS-like symptoms. Because SIVcpz/HIV-1 may disrupt regulation of the gut microbiome and because it has not been possible to sample individual humans pre- and postinfection, we investigated the influence of infection on gut communities through long-term monitoring of chimpanzees from Gombe National Park, Tanzania. SIVcpz infection accelerated the rate of change in gut microbiota composition within individuals for periods of years after the initial infection and led to gut communities marked by high frequencies of pathogen-containing bacterial genera absent from SIVcpz-negative individuals. Our results indicate that immune function maintains temporally stable gut communities that are lost when individuals become infected with SIVcpz.
    Cell host & microbe 09/2013; 14(3):340-5. DOI:10.1016/j.chom.2013.08.005 · 12.19 Impact Factor
  • Source
    • "Like other RNA viruses, human immunodeficiency virus type 1 (HIV-1) is highly mutable, highly adaptable and is capable of rapid evolution (Más et al., 2010). Since the introduction of the most recent common ancestor of the HIV-1 group M in humans (Sharp & Hahn, 2011), the viral population has become extraordinarily diverse (Hemelaar, 2012; Korber et al., 2000). The rate of evolution has been estimated to be 0.0024 substitutions per base pair per year for the HIV-1 gp160 envelope protein and 0.0019 for the HIV-1 gag protein (Korber et al., 2000) (reviewed in Vermund & Leigh-Brown, 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The rapid spread of human immunodeficiency virus type 1 (HIV-1) in humans has been accompanied by continuous extensive genetic diversification of the virus. The aim of this study was to investigate the impact of HIV-1 diversification on HIV-1 replication capacity (RC) and mutational robustness. Thirty-three HIV-1 protease sequences were amplified from three groups of viruses: two naive sample groups isolated 15 years apart plus a third group of protease inhibitor (PI) resistant samples. The amplified proteases were recombined with an HXB2 infectious clone, and RC was determined in MT4 cells. RC was also measured in these three groups after random mutagenesis in vitro using error-prone PCR. No significant RC differences were observed between recombinant viruses from either early or recent naive isolates (p = 0.5729), even though the proteases from the recent isolates had significantly lower sequence conservation scores compared to a subtype B ancestral sequence (p < 0.0001). Randomly mutated recombinant viruses from the three groups exhibited significantly lower RC values than the corresponding wild-type viruses (p < 0.0001). There was no significant difference regarding viral infectivity reduction between viruses carrying randomly mutated naive proteases from early or recent sample isolates (p = 0.8035). Interestingly, a significantly greater loss of RC was observed in the PI resistant protease group (p = 0.0400). These results demonstrate that protease sequence diversification has not affected HIV-1 RC or protease robustness and indicate that proteases carrying PI resistance substitutions are less robust than naive proteases.
    Journal of General Virology 08/2012; 93. DOI:10.1099/vir.0.045492-0 · 3.53 Impact Factor
Show more