Gene Loss and Adaptation to Hominids Underlie the Ancient Origin of HIV-1

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Cell host & microbe (Impact Factor: 12.33). 07/2013; 14(1):85-92. DOI: 10.1016/j.chom.2013.06.002
Source: PubMed


HIV-1 resulted from cross-species transmission of SIVcpz, a simian immunodeficiency virus that naturally infects chimpanzees. SIVcpz, in turn, is a recombinant between two SIV lineages from Old World monkeys. Lentiviral interspecies transmissions are partly driven by the evolution and capacity of viral accessory genes, such as vpx, vpr, and vif, to antagonize host antiviral factors, such as SAMHD1 and the APOBEC3 proteins. We show that vpx, which in other lentiviruses antagonizes SAMHD1, was deleted during the creation of SIVcpz. This genomic deletion resulted in the reconstruction of the overlapping vif gene by "overprinting," creating a unique vif that overlaps in its 3' end with the vpr gene and can antagonize hominid APOBEC3s. Moreover, passage of SIVs through chimpanzees facilitated the subsequent adaptation of HIV-1 to humans. Thus, HIV-1 originated through a series of gene loss and adaptation events that generated its chimpanzee precursor and lowered the species barrier to human infection.

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Available from: Michael Emerman, Apr 02, 2015
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    • "The Vif–A3G interaction was the first Vif–A3 interaction to be studied and it established that Vif inhibits the antiviral activity of A3 enzymes in a species-specific manner (Bogerd et al., 2004; Mangeat et al., 2004; Schrofelbauer et al., 2004; Xu et al., 2004; Etienne et al., 2013; Letko et al., 2013). This means that HIV Vif cannot neutralize A3G from African green monkey (AGM), and AGM SIV Vif cannot neutralize A3G from humans and this has been recognized as a cross-species infection barrier (Bogerd et al., 2004; Mangeat et al., 2004; Schrofelbauer et al., 2004; Xu et al., 2004; Etienne et al., 2013; Letko et al., 2013). Initially, to identify the residues HIV Vif uses to interact with human A3G the human A3G amino acids were replaced with those of AGM or rhesus macaque A3G. "
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    ABSTRACT: The APOBEC3 restriction factors are a family of deoxycytidine deaminases that are able to suppress replication of viruses with a single-stranded DNA intermediate by inducing mutagenesis and functional inactivation of the virus. Of the seven human APOBEC3 enzymes, only APOBEC3-D, -F, -G, and -H appear relevant to restriction of HIV-1 in CD4+ T cells and will be the focus of this review. The restriction of HIV-1 occurs most potently in the absence of HIV-1 Vif that induces polyubiquitination and degradation of APOBEC3 enzymes through the proteasome pathway. To restrict HIV-1, APOBEC3 enzymes must be encapsidated into budding virions. Upon infection of the target cell during reverse transcription of the HIV-1 RNA into (-)DNA, APOBEC3 enzymes deaminate cytosines to form uracils in single-stranded (-)DNA regions. Upon replication of the (-)DNA to (+)DNA, the HIV-1 reverse transcriptase incorporates adenines opposite to the uracils thereby inducing C/G to T/A mutations that can functionally inactivate HIV-1. APOBEC3G is the most studied APOBEC3 enzyme and it is known that Vif attempts to thwart APOBEC3 function not only by inducing its proteasomal degradation but also by several degradation-independent mechanisms, such as inhibiting APOBEC3G virion encapsidation, mRNA translation, and for those APOBEC3G molecules that still become virion encapsidated, Vif can inhibit APOBEC3G mutagenic activity. Although most Vif variants can induce efficient degradation of APOBEC3-D, -F, and -G, there appears to be differential sensitivity to Vif-mediated degradation for APOBEC3H. This review examines APOBEC3-mediated HIV restriction mechanisms, how Vif acts as a substrate receptor for a Cullin5 ubiquitin ligase complex to induce degradation of APOBEC3s, and the determinants and functional consequences of the APOBEC3 and Vif interaction from a biological and biochemical perspective.
    Frontiers in Microbiology 08/2014; 5:450. DOI:10.3389/fmicb.2014.00450 · 3.99 Impact Factor
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    • "To antagonize the anti-viral ability of simian SAMHD1, certain SIVs including SIVrcm degrade SAMHD1 by a viral protein, Vpx. In this regard, Etienne et al. have recently demonstrated that vpx, which is located at the recombination site of SIVrcm and SIVgsn/mon/mus, was lost during the emergence of SIVcpz and that SIVcpz does not possess any anti-CPZ SAMHD1 factor(s)41. When compared to the evolutionary interplay between SIV Vpx and SAMHD1, our findings on the relationship between SIV Nef and tetherin suggest that anti-tetherin ability was more crucial for PLVs, at least for SIVcpz, to adapt and expand in the new host because SIVcpz Nef has successfully inherited its anti-tetherin ability from SIVrcm Nef. "
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    ABSTRACT: Primate lentiviruses including human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses (SIVs) evolved through the acquisition of antagonists against intrinsic host restriction factors, such as tetherin. It is widely accepted that HIV-1 has emerged by zoonotic transmission of SIV in chimpanzee (SIVcpz), and that SIVcpz Nef protein antagonizes chimpanzee tetherin. Although Nef of SIVcpz shares a common ancestor with that of SIVrcm, an SIV in red-capped mangabey (Cercocebus torquatus), it remains unclear whether SIVrcm Nef can antagonize tetherin of its natural host. In this study, we determine the sequence of red-capped mangabey tetherin for the first time and directly demonstrate that SIVrcm Nef is the bona fide antagonist of red-capped mangabey tetherin. These findings suggest that SIVrcm Nef is the functional ancestor of SIVcpz Nef. Moreover, molecular phylogenetic analyses reveal that tetherins of the genus Cercocebus have experienced adaptive evolution, which is presumably promoted by primate lentiviruses.
    Scientific Reports 07/2014; 4:5529. DOI:10.1038/srep05529 · 5.58 Impact Factor
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    • "In a seemingly counterintuitive move, HIV-1 does not encode Vpx that antagonizes a potent restriction factor SAMHD1. Interestingly, vpx deletion during the evolution of SIVcpz (that eventually gave rise to HIV-1) resulted in the creation of a unique vif that can antagonize hominid restriction factor APOBEC3 (Etienne et al., 2013). Whether this curious omission of Vpx contributes to overall HIV-1 fitness, and how much of that advantage is contributed from SAMHD1, remain to be seen. "
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    ABSTRACT: Innate immune recognition is crucial for host responses against viral infections, including infection by human immunodeficiency virus 1 (HIV-1). Human cells detect such invading pathogens with a collection of pattern recognition receptors that activate the production of antiviral proteins, such as the cytokine interferon-type I, to initiate antiviral responses immediately as well as the adaptive immune response for long-term protection. To establish infection in the host, many viruses have thus evolved strategies for subversion of these mechanisms of innate immunity. For example, acute infection by HIV-1 and other retroviruses have long been thought to be non-immunogenic, signifying suppression of host defenses by these pathogens. Studies in the past few years have begun to uncover a multifaceted scheme of how HIV-1 evades innate immune detection, especially of its DNA, by exploiting host proteins. This review will discuss the host mechanisms of HIV-1 DNA sensing and viral immune evasion, with a particular focus on TREX1, three prime repair exonuclease 1, a host 3' exonuclease (also known as DNase III).
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