CD4 down-regulation by nef alleles isolated from human immunodeficiency virus type 1-infected individuals.

Mariani, Roberto; Skowroński, Jacek

doi:10.1073/pnas.90.12.5549

Cited by 173 publications

(164 citation statements)

References 27 publications

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“…Second, it is thought to activate quiescent cells (Spina et al 1994); Baur et al (1994) postulate that Nef activates quiescent cells depending on the subcellular pattern of expression of the gene. It downregulates CD4 expression on the surface of infected cells (Mariani & Skowronski 1993). Finally, there is evidence that Nef downregulates MHC I in vitro (Collins et al 1998), and that it enhances apoptosis (Xu et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Intra-host competition between nef–defective escape mutants and wild–type human immunodeficiency virus type 1

Altes

Jansen

2000

Proc. R. Soc. Lond. B

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Various forms of nef genes with deletions at conserved positions along the sequence have been reported to persist in human immunode¢ciency virus type 1 infected patients. We investigate the forces maintaining such variants in the proviral population. The main selection pressures are preservation of function and host immune response. The crippled Nef protein might have fewer epitopes, and as such be less visible to the speci¢c immune response, but it will lose some function. Does a trade-o¡ between avoidance of the immune response and loss of function explain the dynamics of the crippled virus found in the patients ? To answer this question, we formulated a deterministic model of the virus^host interactions. We found that when the crippled protein presents few epitopes and su¡ers little loss of function, the two viral types can coexist. Otherwise, the wild-type comes to prevail. The mutant form might initially dominate, but as the selective pressure by the CD8+ T cells decreases over the course of infection, the advantage for the crippled form of losing epitopes disappears. Hence, we go from a situation of coexistence of wild-type and mutant, to a situation of only full-length nef. The results are discussed in the context of the suggested use of live attenuated vaccines having deletions in nef.

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Section: Introductionmentioning

confidence: 99%

Intra-host competition between nef–defective escape mutants and wild–type human immunodeficiency virus type 1

Altes

Jansen

2000

Proc. R. Soc. Lond. B

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“…Nef induces the clathrin-mediated endocytosis and degradation of cell surface CD4 (2)(3)(4)(5), and also triggers the down-regulation of other cell surface molecules, including MHC class I antigens (6), which may facilitate the evasion of an antiviral immune response (7). Nef also modulates T cell function and apoptosis by engaging components of cellular signaling pathways, including Vav, Pak2, ASK1, and the DOCK2-ELMO1 complex (8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

Dynamin 2 is required for the enhancement of HIV-1 infectivity by Nef

Pizzato

Helander

Попова

et al. 2007

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

110

150

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Nef is a virulence factor of HIV-1 and other primate lentiviruses that is crucial for rapid progression to AIDS. In cell culture, Nef increases the infectivity of HIV-1 progeny virions by an unknown mechanism. We now show that dynamin 2 (Dyn2), a key regulator of vesicular trafficking, is a binding partner of Nef that is required for its ability to increase viral infectivity. Dominant-negative Dyn2 or the depletion of Dyn2 by small interfering RNA potently inhibited the effect of Nef on HIV-1 infectivity. Furthermore, in Dyn2-depleted cells, this function of Nef could be rescued by ectopically expressed Dyn2 but not by Dyn1, a closely related isoform that does not bind Nef. The infectivity enhancement by Nef also depended on clathrin, because it was diminished in clathrin-depleted cells and profoundly inhibited in cells expressing the clathrin-binding domain of AP180, which blocks clathrin-coated pit formation but not clathrin-independent endocytosis. Together, these findings imply that the infectivity enhancement activity of Nef depends on Dyn2-and clathrin-mediated membrane invagination events.HIV accessory protein ͉ host factor ͉ virion infectivity

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“…Endocytosis may be classified into two categories, clathrin dependent and independent. The role of Nef in inducing clathrin-dependent endocytosis of some surface receptors, as CD4 (Aiken et al, 1994;Chaudhuri et al, 2007;Garcia and Miller, 1991;Mariani and Skowronski, 1993), triggering the de novo formation of clathrin coated pits and acting as a connector between receptor cargo and the endocytic machinery has been addressed here. Dyn2 was identified as a Nef binding partner through immunopreciptation assays, and is intrinsically related to clathrin-dependent endocytosis (Pizzato et al, 2007).…”

Section: Nef and Virus Assemblymentioning

confidence: 99%

Functions of the Lentiviral Accessory Protein Nef During the Distinct Steps of HIV and SIV Replication Cycle

Costa¹,

Mendonça²,

Sampaio³

2011

HIV and AIDS - Updates on Biology, Immunology, Epidemiology and Treatment Strategies

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CD4 down-regulation by nef alleles isolated from human immunodeficiency virus type 1-infected individuals.

Cited by 173 publications

References 27 publications

Intra-host competition between nef–defective escape mutants and wild–type human immunodeficiency virus type 1

Intra-host competition between nef–defective escape mutants and wild–type human immunodeficiency virus type 1

Dynamin 2 is required for the enhancement of HIV-1 infectivity by Nef

Functions of the Lentiviral Accessory Protein Nef During the Distinct Steps of HIV and SIV Replication Cycle

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