Expression of Nef Downregulates CXCR4, the Major Coreceptor of Human Immunodeficiency Virus, from the Surfaces of Target Cells and Thereby Enhances Resistance to Superinfection

Venzke, Stephanie; Michel, Nico; Allespach, Ina; Fackler, Oliver T.; Keppler, Oliver T.

doi:10.1128/jvi.01556-06

Cited by 75 publications

(77 citation statements)

References 78 publications

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“…Studies of transcription from preintegrated cDNA can be modeled by blocking integration, either through the use of defective integrase or by integrase strand transfer inhibitors, as the patterns of transcription and translation observed in these contexts are similar to those seen in studies of transcription prior to integration (21,56,58). Such studies demonstrated that preintegration translation of nef variously downregulates CD4, CXCR4, and CCR5 (18,45), which may serve to limit signal transduction through these receptors (59) and possibly limit viral superinfection (31,45,49,50). Similar studies have also demonstrated that preintegration translation of rev might limit superinfection of cells at the level of integration (29,30).…”

Section: Discussionmentioning

confidence: 99%

Transcription of Preintegrated HIV-1 cDNA Modulates Cell Surface Expression of Major Histocompatibility Complex Class I via Nef

Sloan

Kuhl

Donahue

et al. 2011

J Virol

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Section: Discussionmentioning

confidence: 99%

Transcription of Preintegrated HIV-1 cDNA Modulates Cell Surface Expression of Major Histocompatibility Complex Class I via Nef

Sloan

Kuhl

Donahue

et al. 2011

J Virol

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“…PBL were grown in RPMI 1640 medium containing 10% FCS in the presence of PHA (PHA-P) (10 g/ml) (Wako Pure Chemical) and recombinant human IL-2 (20 U/ml; Sigma-Aldrich) for 5 days. PBL (5 ϫ 10 6 ) were nucleofected with pcDNA3 empty vector (3 g) or Myc-tagged STAP-2 (3 g) using a human T cell Nucleofector kit (Nucleofector program T-23; Amaxa Biosystems) (21).…”

Section: Cell Culture Cell Purification and Treatmentmentioning

confidence: 99%

Signal-Transducing Adaptor Protein-2 Regulates Stromal Cell-Derived Factor-1α-Induced Chemotaxis in T Cells

Sekine

Ikeda

Tsuji

et al. 2009

The Journal of Immunology

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Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin and Src homology 2-like domains, as well as a YXXQ motif in its C-terminal region. Our previous studies revealed that STAP-2 regulates integrin-mediated T cell adhesion. In the present study, we find that STAP-2 expression affects Jurkat T cell migration after stromal cell-derived factor-1α (SDF-1α)-treatment. Furthermore, STAP-2-deficient T cells exhibit reduced cell migration after SDF-1α-treatment. Importantly, overexpression of STAP-2 in Jurkat T cells induces activation of small guanine triphosphatases, such as Rac1 and Cdc42. Regarding the mechanism for this effect, we found that STAP-2 associates with Vav1, the guanine-nucleotide exchanging factor for Rac1, and enhances downstream Vav1/Rac1 signaling. These results reveal a novel STAP-2-mediated mechanism for the regulation of SDF-1α-induced chemotaxis of T cells via activation of Vav1/Rac1 signaling.

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“…One of the best-characterized functions of Nef concerns its ability to affect the trafficking of proteins expressed at the cell surface. Nef was initially shown to downregulate the cell surface expression levels of proteins such as CD4 and a subset of major histocompatibility complex class I molecules (22,38,76), but additional studies revealed that the expression of HIV but also SIV Nef promotes the downregulation of other cell surface proteins, such as mature major histocompatibility complex class II molecules, CD28, CD8, CXCR4, and CCR5, and the transferrin receptor (43,55,58,59,83,84,87; for a review, see reference 48). The Nef-dependent downregulation of CD4 in virus-producing cells was shown to favor efficient HIV-1 envelope glycoprotein incorporation into virions by preventing the formation of CD4/gp120 complexes at the cell surface (6,26,73).…”

mentioning

confidence: 99%

Human Immunodeficiency Virus Type 1 Nef Incorporation into Virions Does Not Increase Infectivity

Laguette

Bénichou

Basmaciogullari

2009

J Virol

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The viral protein Nef contributes to the optimal infectivity of human and simian immunodeficiency viruses. The requirement for Nef during viral biogenesis particles suggests that Nef might play a role in this process. Alternatively, because Nef is incorporated into viruses, it might play a role when progeny virions reach target cells. We challenged these hypotheses by manipulating the amounts of Nef incorporated in viruses while keeping its expression level constant in producer cells. This was achieved by forcing the incorporation of Nef into viral particles by fusing a Vpr sequence to the C-terminal end of Nef. A cleavage site for the viral protease was introduced between Nef and Vpr to allow the release of Nef fragments from the fusion protein during virus maturation. We show that the resulting Nef-CS-Vpr fusion partially retains the ability of Nef to downregulate cell surface CD4 and that high amounts of Nef-CS-Vpr are incorporated into viral particles compared with what is seen for wild-type Nef. The fusion protein is processed during virion maturation and releases Nef fragments similar to those found in viruses produced in the presence of wild-type Nef. Unlike viruses produced in the presence of wild-type Nef, viruses produced in the presence of Nef-CS-Vpr do not have an increase in infectivity and are as poorly infectious as viruses produced in the absence of Nef. These findings demonstrate that the presence of Nef in viral particles is not sufficient to increase human immunodeficiency virus type 1 infectivity and suggest that Nef plays a role during the biogenesis of viral particles.

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Expression of Nef Downregulates CXCR4, the Major Coreceptor of Human Immunodeficiency Virus, from the Surfaces of Target Cells and Thereby Enhances Resistance to Superinfection

Cited by 75 publications

References 78 publications

Transcription of Preintegrated HIV-1 cDNA Modulates Cell Surface Expression of Major Histocompatibility Complex Class I via Nef

Transcription of Preintegrated HIV-1 cDNA Modulates Cell Surface Expression of Major Histocompatibility Complex Class I via Nef

Signal-Transducing Adaptor Protein-2 Regulates Stromal Cell-Derived Factor-1α-Induced Chemotaxis in T Cells

Human Immunodeficiency Virus Type 1 Nef Incorporation into Virions Does Not Increase Infectivity

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