Vpu and Tsg101 Regulate Intracellular Targeting of the Human Immunodeficiency Virus Type 1 Core Protein Precursor Pr55
            <sup>
              <i>gag</i>
            </sup>

Harila, Kirsi; Prior, Ian A.; Sjöberg, Mathilda; Salminen, Antti; Hinkula, Jorma; Suomalainen, Maarit

doi:10.1128/jvi.80.8.3765-3772.2006

Cited by 47 publications

(64 citation statements)

References 47 publications

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“…While some studies indicate that internal endosomal compartments, notably LE/MVB, represent early intermediates where Gag is first targeted prior to budding at the PM (12,21,30,39,45,46,48,49,54), more recent studies support a model in which Gag-mediated assembly mainly occurs at the PM with accumulation of Gag and viral particles in LE/MVB resulting from an internalization process from the cell surface (22,24,34,51). One aspect that has complicated interpretation of the data is that, initially, most studies evaluated Gag localization at steady state by electron or fluorescence microscopy (12,30,38,39,45,48,54); the observation that Gag or viral particles accumulated in LE/MVB did not absolutely mean that the precursor was first targeted or assembled at this location nor did it provide any information about the route that Gag follows before reaching its steady-state subcellular destination.…”

Section: Discussionmentioning

confidence: 98%

“…In that regard, it was recently reported that the mere fact of changing the length of a linker sequence between Gag and a carboxy-terminal tetracysteine tag drastically modified the localization of Gag from the PM to intracellular compartments (51). Furthermore, the presence of a carboxy-terminal hemagglutinin tag was sufficient to inhibit the endocytosis of PM-associated Pr55 gag (22). Moreover, it was reported that introduction of mutations that did not alter Gag amino acid sequence but modified its mRNA export pathway (passing from Rev dependent to constitutive transport element [CTE] dependent) affected its steady-state localization (3,57).…”

Section: Discussionmentioning

confidence: 99%

“…In this model, LE/MVB compartments represent early intermediates where assembly and budding can take place. In contrast, the other model postulates that newly synthesized Pr55 gag is first targeted to the PM, where viral assembly and release occur; nonreleased Gag products are subsequently internalized to-wards LE/MVB (22,24,34,51) in a process that is sensitive to endocytosis inhibitors (24,34).…”

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confidence: 99%

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Productive Human Immunodeficiency Virus Type 1 Assembly Takes Place at the Plasma Membrane

Finzi

Orthwein

Mercier

et al. 2007

J Virol

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Gag proteins are necessary and sufficient to direct human immunodeficiency virus type 1 (HIV-1) particle assembly and budding. Recent evidence suggests that Gag targeting to late endosomal/multivesicular body (LE/MVB) compartments occurs prior to viral particle budding at the plasma membrane (PM). However, the route that Gag follows before reaching its steady-state destinations still remains a subject of debate. Using a subcellular fractionation method that separates PM from LE/MVB combined with pulse-chase labeling, we analyzed Gag trafficking in HIV-1-producing HEK 293T cells. Our results reveal that the majority of newly synthesized Gag is primarily targeted to the PM. While PM-targeted Gag was efficiently released, a significant fraction of the remaining cell surface-associated Gag was found to be subsequently internalized to LE/MVB, where it accumulated, thus accounting for the majority of LE/MVB-associated Gag. Importantly, this accumulation of Gag in LE/MVB was found to be cholesterol dependent since it was sensitive to the sterol-binding drugs filipin and methyl-␤-cyclodextrin. These results point towards the PM as being the primary site of productive HIV-1 assembly in cells that also support Gag accumulation in intracellular compartments.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Productive Human Immunodeficiency Virus Type 1 Assembly Takes Place at the Plasma Membrane

Finzi

Orthwein

Mercier

et al. 2007

J Virol

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“…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%

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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“…Newly synthesized Gag is initially transported to the extracellular membrane, where the endocytic uptake of Gag is dismissed in the presence of HIV-1 Vpu (490). In contrast, the absence of HIV-1 Vpu causes a significant amount of Gag to be redistributed to internal membranes for endocytosis (490). Interestingly, Vpu start codon mutants can rescue the impaired viral infectivity of a matrix mutant with the amino acid substitution L30E (491).…”

Section: Vpu-ubp-matrix Gag Associationmentioning

confidence: 99%

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

Clercq

2016

Microbiol Mol Biol Rev

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SUMMARYThe HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-wide perspective, a hypothesis can be worked out to determine whether 16 HIV proteins could develop 120 possible pairwise associations either by physical interactions or by functional associations mediated via HIV or host molecules. Here, we present the first systematic review of experimental evidence on HIV genome-wide protein associations using a large body of publications accumulated over the past 3 decades. Of 120 possible pairwise associations between 16 HIV proteins, at least 34 physical interactions and 17 functional associations have been identified. To achieve efficient viral replication and infection, HIV protein associations play essential roles (e.g., cleavage, inhibition, and activation) during the HIV life cycle. In either a dispensable or an indispensable manner, each HIV protein collaborates with another viral protein to accomplish specific activities that precisely take place at the proper stages of the HIV life cycle. In addition, HIV genome-wide protein associations have an impact on anti-HIV inhibitors due to the extensive cross talk between drug-inhibited proteins and other HIV proteins. Overall, this study presents for the first time a comprehensive overview of HIV genome-wide protein associations, highlighting meticulous collaborations between all viral proteins during the HIV life cycle.

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Vpu and Tsg101 Regulate Intracellular Targeting of the Human Immunodeficiency Virus Type 1 Core Protein Precursor Pr55 ^gag

Abstract: Assembly of human immunodeficiency virus type 1 (HIV-1

Cited by 47 publications

References 47 publications

Productive Human Immunodeficiency Virus Type 1 Assembly Takes Place at the Plasma Membrane

Productive Human Immunodeficiency Virus Type 1 Assembly Takes Place at the Plasma Membrane

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

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

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Vpu and Tsg101 Regulate Intracellular Targeting of the Human Immunodeficiency Virus Type 1 Core Protein Precursor Pr55 gag

Abstract: Assembly of human immunodeficiency virus type 1 (HIV-1

Cited by 47 publications

References 47 publications

Productive Human Immunodeficiency Virus Type 1 Assembly Takes Place at the Plasma Membrane

Productive Human Immunodeficiency Virus Type 1 Assembly Takes Place at the Plasma Membrane

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

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

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Product

Resources

About

Vpu and Tsg101 Regulate Intracellular Targeting of the Human Immunodeficiency Virus Type 1 Core Protein Precursor Pr55 ^gag