Genetic organization of a chimpanzee lentivirus related to HIV-1

Huet, Thierry; Cheynier, Rémi; Meyerhans, Andreas; Roelants, Georges E.; Wain‐Hobson, Simon

doi:10.1038/345356a0

Cited by 364 publications

(242 citation statements)

References 28 publications

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“…2 is an 81-amino acid type I integral membrane phosphoprotein expressed by human immunodeficiency virus type 1 (HIV-1) (1, 2) and several simian immunodeficiency viruses (3)(4)(5)(6). Vpu is not incorporated into virus particles (7), indicating that it acts exclusively in virus-producer cells.…”

Section: Viral Protein U (Vpu)mentioning

confidence: 99%

HIV-1 Accessory Protein Vpu Internalizes Cell-surface BST-2/Tetherin through Transmembrane Interactions Leading to Lysosomes

Iwabu

Fujita

Kinomoto

et al. 2009

Journal of Biological Chemistry

207

298

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Bone marrow stromal antigen 2 (BST-2, also known as tetherin) is a recently identified interferon-inducible host restriction factor that can block the production of enveloped viruses by trapping virus particles at the cell surface. This antiviral effect is counteracted by the human immunodeficiency virus type 1 (HIV-1) accessory protein viral protein U (Vpu). Here we show that HIV-1 Vpu physically interacts with BST-2 through their mutual transmembrane domains and leads to the degradation of this host factor via a lysosomal, not proteasomal, pathway. The degradation is partially controlled by a cellular protein, ␤-transducin repeat-containing protein (␤TrCP), which is known to be required for the Vpu-induced degradation of CD4. Importantly, targeting of BST-2 by Vpu occurs at the plasma membrane followed by the active internalization of this host protein by Vpu independently of constitutive endocytosis. Thus, the primary site of action of Vpu is the plasma membrane, where Vpu targets and internalizes cell-surface BST-2 through transmembrane interactions, leading to lysosomal degradation, partially in a ␤TrCP-dependent manner. Also, we propose the following configuration of BST-2 in tethering virions to the cell surface; each of the dimerized BST-2 molecules acts as a bridge between viral and cell membranes. Viral protein U (Vpu)2 is an 81-amino acid type I integral membrane phosphoprotein expressed by human immunodeficiency virus type 1 (HIV-1) (1, 2) and several simian immunodeficiency viruses (3-6). Vpu is not incorporated into virus particles (7), indicating that it acts exclusively in virus-producer cells. Indeed, Vpu is known to play two distinct roles during the later stages of infection. First, Vpu interacts with newly synthesized CD4 molecules complexed with the gp160 envelope glycoprotein precursor in the endoplasmic reticulum (8, 9) and recruits the ␤-transducin repeat-containing protein 1 (␤TrCP-1) subunit of the Skp1-Cullin1-F-box ubiquitin ligase complex (10) as well as ␤TrCP-2 (11) through its phosphoserine residues at positions 52 and 56 in the cytoplasmic (CT) domain (12,13). This event results in proteasome-mediated degradation of CD4 (10, 14, 15) allowing gp160 to resume transport toward the cell surface for virion incorporation. Second, Vpu mediates the enhancement of virion release (16 -18) in a cell type-dependent manner (e.g. HeLa cells require Vpu, whereas COS7 cells do not (19,20)), and its absence leads to the accumulation of viral particles at the cell surface (21).In contrast to the effect of Vpu on CD4 degradation, little had been known about the mechanism by which Vpu enhances the release of virions. The finding that HeLa-COS7 heterokaryons exhibited HeLa-type properties suggested that Vpu-responsive HeLa cells might harbor endogenous a restriction factor(s) that could be counteracted by this viral protein (22), as seen in Vifresponsive cells harboring the antiretroviral factor APOBEC3G counteracted by Vif (23). Neil et al. (24) showed that Vpu-deficient viral particles accumulated ...

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Section: Viral Protein U (Vpu)mentioning

confidence: 99%

HIV-1 Accessory Protein Vpu Internalizes Cell-surface BST-2/Tetherin through Transmembrane Interactions Leading to Lysosomes

Iwabu

Fujita

Kinomoto

et al. 2009

Journal of Biological Chemistry

207

298

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“…Recently, a lentivirus has been identified in wild chimpanzees (Pan troglodytes troglodytes) (SlVepz) (Peeters et al, 1989;Huet et al, 1990). Whereas SIVmac is 0001-0807 © 1992 SGM closely related to HIV-2, and SIVcp z to HIV-1 (Huet et al, 1990), SIVag m and SIVmn d appear both equidistant from both HIV-1 and HIV-2 (Gardner & Luciw, 1988).…”

Section: Introductionmentioning

confidence: 99%

Differential inhibitory effects of TIBO derivatives on different strains of simian immunodeficiency virus

Debyser

Vreese

Pauwels

et al. 1992

Journal of General Virology

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“…For instance, it seems highly probably that HIV arose from a similar virus infecting primates in Central Africa. Various HIV-like retroviruses have been described, including chimpanzee viruses [19]. Initial infection of an occasional human following direct contact with an infected primate may have caused sporadic AIDS, which would have passed unnoticed, the virus not being transmitted from human to human, as is usual in infections derived directly from animals.…”

Section: The Block In Terms Of Pathogenesismentioning

confidence: 99%

The origin of major human infections and the crucial role of person-to-person spread

Mims

1991

Epidemiol. Infect.

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In discussions of the origin of new infectious diseases, prominence is usually given to dramatic infections acquired from animals (Lassa fever, Marburg and Ebola viruses) or from the environment (legionellosis). But these infections do not spread from human to human, and their impact on mankind can never be catastrophic. If a new infectious agent is to pose a major threat to the human species, it will need to kill tens or hundreds of millions of people over a short period of time (a few years), before vaccines and antimicrobial agents can be developed or effective blocks to transmission established. The 1918 influenza pandemic (total deaths about 20 million) almost came into this world-shaking category, but many of the deaths were presumably due to secondary bacterial pneumonia and this was the pre-antibiotic era. A similar airborne pandemic occurring today could spread globally within weeks by air transport and would have a greater impact. Smallpox arose long before the world became one from an infectious disease point of view, and although it caused devastating epidemics it did not have the opportunity to develop into the ‘major threat’ category. A significant proportion of people recovered, less virulent strains of virus (variola minor) appeared, and an effective vaccine not only kept it under control in many continents but finally eliminated it from the world. The plague (Yersinia pestis) influenced the course of history in Asia and Europe [1] but oven in its respiratory form could not in those days be transferred rapidly from continent to continent.

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Genetic organization of a chimpanzee lentivirus related to HIV-1

Cited by 364 publications

References 28 publications

HIV-1 Accessory Protein Vpu Internalizes Cell-surface BST-2/Tetherin through Transmembrane Interactions Leading to Lysosomes

HIV-1 Accessory Protein Vpu Internalizes Cell-surface BST-2/Tetherin through Transmembrane Interactions Leading to Lysosomes

Differential inhibitory effects of TIBO derivatives on different strains of simian immunodeficiency virus

The origin of major human infections and the crucial role of person-to-person spread

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