Functional role of human immunodeficiency virus type 1 vpu.

Terwilliger, Ernest F.; Cohen, Éric A.; Lu, Yichen; Sodroski, Joseph; Haseltine, William A.

doi:10.1073/pnas.86.13.5163

Cited by 256 publications

(216 citation statements)

References 30 publications

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“…Bst-2 expression in A3.01 (lanes 3 and 4) and Jurkat cells (lanes 7 and 8) was near or below the limit of detection even after IFN␣ stimulation. This result is surprising because both A3.01 and Jurkat T cell lines were found to require Vpu for efficient virus release (1,10). FACS analyses confirmed the absence of cell surface Bst-2 in Jurkat cells whereas H9 cells were positive for surface Bst-2 (Fig.…”

Section: Hiv-1 Vpu Enhances the Release Of Virions From Infected Cellsmentioning

confidence: 75%

“…CD317 ͉ host restriction ͉ tetherin ͉ virus assembly V pu is an 81-aa type 1 integral membrane protein (1, 2) that has been shown to cause proteasomal degradation of CD4 (3,4), enhance the release of virions from infected cells (5), and prevent endocytosis of nascent viral particles (6)(7)(8)(9)(10)(11). These latter biological activities of Vpu are mechanistically distinct from CD4 degradation and involve different structural domains in Vpu.…”

Section: Hiv-1 Vpu Enhances the Release Of Virions From Infected Cellsmentioning

confidence: 99%

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Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

Miyagi

Andrew

Kao

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

205

281

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HIV-1 Vpu enhances the release of virions from infected cells. Recent work identified Bst-2/CD317/tetherin as a host factor whose inhibitory activity on viral release is counteracted by Vpu. A current working model proposes that Bst-2 inhibits virus release by tethering viral particles to the cell surface. Here, we analyzed endogenous Bst-2 with respect to its effect on virus release from HeLa cells, T cells, and macrophages. We noted significant cell type-dependent variation in Bst-2 expression. Vpu caused a reduction in Bst-2 expression in transfected HeLa cells and long-term infected macrophages. However, Vpu expression did not result in cell surface down-modulation of Bst-2 or a reduction in intracellular Bst-2 expression in CEMx174 or H9 cells, yet virus replication in these cells was Vpu-responsive. Surprisingly, Bst-2 was undetectable in cell-free virions that were recovered from the surface of HeLa cells by physical shearing, suggesting that a tethering model may not explain all of the functional properties of Bst-2. Taken together we conclude that enhancement of virus release by Vpu does not, at least in CEMx174 and H9 cells, require cell surface down-modulation or intracellular depletion of Bst-2, nor does it entail exclusion of Bst-2 from viral particles.

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Section: Hiv-1 Vpu Enhances the Release Of Virions From Infected Cellsmentioning

confidence: 75%

Section: Hiv-1 Vpu Enhances the Release Of Virions From Infected Cellsmentioning

confidence: 99%

Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

Miyagi

Andrew

Kao

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

205

281

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“…If rates of CTL-dependent killing are much faster in SIV infections, then it would suggest that rates of CTLindependent killing must be slower. Although there are some in vitro data that are consistent with this hypothesis showing that both activation-induced cell death (40) and viral cytotoxicity (41,42) may be reduced in SIV infection, it remains a hypothesis to be tested in studies that evaluate the in vivo CTL-independent death rate of productively infected cells in humans and nonhuman primate models.…”

Section: Discussionmentioning

confidence: 85%

In vivoCD8⁺T cell control of immunodeficiency virus infection in humans and macaques

Asquith

McLean

2007

Proc. Natl. Acad. Sci. U.S.A.

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Forty million people are estimated to be infected with HIV-1, and only a small fraction of those have access to life-prolonging antiretroviral treatment. As the epidemic grows there is an urgent need for effective therapeutic and prophylactic vaccines. Nonhuman primate models of immunodeficiency virus infection are essential for the preclinical evaluation of candidate vaccines. To interpret the results of these trials, comparative studies of the human and macaque immune responses are needed. Despite the widespread use of macaques to evaluate vaccines designed to elicit a CD8 ؉ cytotoxic T lymphocyte (CTL) response, the efficiency with which CTL control immunodeficiency virus infections has not been compared between humans and macaques, largely because of difficulties in assaying the functional CTL response. We recently developed a method for estimating the rate at which CTLs kill cells productively infected with HIV-1 in humans in vivo. Here, using the same technique, we quantify the rate at which CTLs kill infected cells in macaque models of HIV infection. We show that CTLs kill productively infected cells significantly faster (P ‫؍‬ 0.004) and that escape variants have significantly higher fitness costs (P ‫؍‬ 0.003) in macaques compared with humans. These results suggest that it may be easier to elicit a protective CTL response in macaques than in humans and that vaccine studies conducted in macaques need to be interpreted accordingly.human immunodeficiency virus ͉ simian immunodeficiency virus ͉ cytotoxic T lymphocyte ͉ vaccine ͉ viral escape S imian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) infection of nonhuman primates, notably rhesus macaques (Macaca mulatta) and pigtail macaques (Macaca nemestrina), reproduce many of the key elements of HIV infection of humans, including CD4 ϩ cell depletion and an AIDS-like syndrome. Importantly, for appraising vaccine efficacy, macaques and humans have similar immune systems (1). However, it has been difficult to compare immune control of immunodeficiency viruses in humans and macaques. A number of commonly used SHIV strains (SHIV-89.6P, SHIV-DH12R, and SHIV-KU) are more susceptible to antibody neutralization than HIV-1, and it has therefore been suggested that they are poor systems for testing vaccines designed to elicit an antibody response (2). The efficiency with which CD8 ϩ cytotoxic T lymphocytes (CTLs) control immunodeficiency virus infections has not been compared between humans and macaques, largely because of difficulties in assaying the functional CTL response (3). A method for quantifying CTL lytic function in vivo (4, 5) now makes this comparison possible. ResultsThe rate at which a CTL escape variant grows out and replaces the wild-type (WT) strain, ''the rate of escape,'' is determined by the balance between the rate of CTL killing evaded by the escape variant and the fitness cost of the variant (see Methods). By quantifying the rate of escape and the fitness cost of known CTL escape variants the rate of killing of prod...

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“…HIV‐1 Viral protein U (Vpu) 59, 60 is renowned for its role in proteasomal degradation of CD4 61, 62 and enhancement of HIV‐1 release from infected cells 63, 64, 65 in a cell type‐dependent manner 66. In 2008, two independent laboratories showed that cell type‐specific expression of BST‐2 correlates with Vpu‐dependent release of HIV‐1.…”

Section: Viral Antagonists Of Bst‐2 and Neutralization Of Bst‐2 Antivmentioning

confidence: 99%

The role of BST‐2/Tetherin in host protection and disease manifestation

Mahauad‐Fernandez

Okeoma

2015

Immunity, Inflammation and Disease

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Host cells respond to viral infections by activating immune response genes that are not only involved in inflammation, but may also predispose cells to cancerous transformation. One such gene is BST‐2, a type II transmembrane protein with a unique topology that endows it tethering and signaling potential. Through this ability to tether and signal, BST‐2 regulates host response to viral infection either by inhibiting release of nascent viral particles or in some models inhibiting viral dissemination. However, despite its antiviral functions, BST‐2 is involved in disease manifestation, a function linked to the ability of BST‐2 to promote cell‐to‐cell interaction. Therefore, modulating BST‐2 expression and/or activity has the potential to influence course of disease.

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Functional role of human immunodeficiency virus type 1 vpu.

Cited by 256 publications

References 30 publications

Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

In vivoCD8⁺T cell control of immunodeficiency virus infection in humans and macaques

The role of BST‐2/Tetherin in host protection and disease manifestation

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Functional role of human immunodeficiency virus type 1 vpu.

Cited by 256 publications

References 30 publications

Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

In vivoCD8+T cell control of immunodeficiency virus infection in humans and macaques

The role of BST‐2/Tetherin in host protection and disease manifestation

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In vivoCD8⁺T cell control of immunodeficiency virus infection in humans and macaques