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: 9.47). 09/2011; 1(1):a006841. DOI: 10.1101/cshperspect.a006841
Source: PubMed


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.


Available from: Paul M Sharp, Jul 30, 2014
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    • "An intriguing possibility is that non-canonical cofactors act to increase the evolvability of their Vif partner, enabling Vif proteins to retain activity with otherwise lethal mutations during transitions to more-fit states. Restriction factors are a major barrier to zoonosis (Sharp and Hahn, 2011), and a Vif protein able to adapt more quickly to a new host's A3 proteins should grant the lentivirus a competitive advantage in zoonotic transmission, as well as in populations with diverse restriction factor haplotypes (Binka et al., 2012; Ooms et al., 2013). Whether gaining an interaction partner makes a viral protein more robust to mutation is debatable, as the benefits of stabilization via the interaction may be outweighed by the mutational constrains imposed by the interaction itself. "
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    ABSTRACT: HIV-1 encodes the accessory protein Vif, which hijacks a host Cullin-RING ubiquitin ligase (CRL) complex as well as the non-canonical cofactor CBFβ, to antagonize APOBEC3 antiviral proteins. Non-canonical cofactor recruitment to CRL complexes by viral factors, to date, has only been attributed to HIV-1 Vif. To further study this phenomenon, we employed a comparative approach combining proteomic, biochemical, structural, and virological techniques to investigate Vif complexes across the lentivirus genus, including primate (HIV-1 and simian immunodeficiency virus macaque [SIVmac]) and non-primate (FIV, BIV, and MVV) viruses. We find that CBFβ is completely dispensable for the activity of non-primate lentiviral Vif proteins. Furthermore, we find that BIV Vif requires no cofactor and that MVV Vif requires a novel cofactor, cyclophilin A (CYPA), for stable CRL complex formation and anti-APOBEC3 activity. We propose modular conservation of Vif complexes allows for potential exaptation of functions through the acquisition of non-CRL-associated host cofactors while preserving anti-APOBEC3 activity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 05/2015; 11(8). DOI:10.1016/j.celrep.2015.04.038 · 8.36 Impact Factor
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    • "The most prevalent of these (HIV-1, group M) was transmitted into humans approximately 100 years ago and is responsible for well over 90% of global HIV infections (Worobey et al., 2008). HIV- 2 also causes AIDS but is associated with lower viral loads and reduced person-to-person transmission rates, and has not spread substantially from West Africa (Reeves and Doms, 2002; Sharp and Hahn, 2011). Overall, approximately 35 million people are currently infected with HIV and a similar number have already died of AIDS (UNAIDS, 2013). "
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    ABSTRACT: Many important aspects of human retroviral infections cannot be fully evaluated using only in vitro systems or unmodified animal models. An alternative approach involves the use of humanized mice, which consist of immunodeficient mice that have been transplanted with human cells and/or tissues. Certain humanized mouse models can support robust infection with human retroviruses including different strains of human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV). These models have provided wide-ranging insights into retroviral biology, including detailed information on primary infection, in vivo replication and pathogenesis, latent/persistent reservoir formation, and novel therapeutic interventions. Here we describe the humanized mouse models that are most commonly utilized to study retroviral infections, and outline some of the important discoveries that these models have produced during several decades of intensive research.
    Virology 02/2015; 479-480. DOI:10.1016/j.virol.2015.01.017 · 3.32 Impact Factor
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    • "La consommation fréquente de « viande de brousse » (dont primates) en Afrique de l'Ouest rend tout à fait possible des transferts de parasites entre faune sauvage et homme, soit au cours de morsure d'animaux vivants, soit au cours de dépeçage d'animaux morts (Peeters et al., 2002). L'analyse détaillée de ces phylogénies a montré en particulier qu'il y a eu pas moins de six événements indépendants de transferts de VIS à l'homme (Sharp et Hanh, 2011). Enfin, ces analyses ont également permis de dater ces événements de transferts jusqu'au début du XX e siècle (Worobey et al., 2008), en accord avec le plus vieux cas connu d'infection humaine par VIH datant de 1959 (soit plus de vingt ans avant le démarrage de la pandémie que l'on connaît aujourd'hui (Zhu et al., 1998). "
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    ABSTRACT: Le syndrome d'immunodéficience acquise constitue, avec le paludisme et la tuberculose, une des trois grandes maladies prioritaires pour l'Organisation mondiale de la santé. La difficulté à le combattre provient de la capacité du virus VIH à concilier des pressions évolutives parfois contradictoires et à garder ainsi un coup d'avance sur le système immunitaire.
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