The effect of the membrane-proximal tyrosine-based sorting signal of HIV-1 gp41 on viral infectivity depends on sequences within gp120.

The effect of the membrane-proximal tyrosine-based sorting signal of HIV-1 gp41 on viral infectivity depends on sequences within gp120. Research Abstract Details 

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The effect of the membrane-proximal tyrosine-based sorting signal of HIV-1 gp41 on viral infectivity depends on sequences within gp120. Abstract Text:

John R Day,Nanette Van Damme,John C Guatelli,

The cytoplasmic domain of the HIV-1 Env glycoprotein (gp41) contains sequences that affect the trafficking of Env within the host cell. We previously showed that the membrane-proximal tyrosine-based adaptor protein (AP)-binding signal of gp41 (Y712XXL) is required for optimal viral infectivity and entry into target cells. Because these effects were not attributable to an effect on the incorporation of Env into virions, we hypothesized that they involved targeting of viral assembly to specific endosomal membranes that conferred greater fusogenicity. To further elaborate this hypothesis, we mutated the C-terminal leucine-based AP-binding signal of gp41 (LL855/856). In contrast to Env Y712, the leucine signal was dispensable for viral infectivity in both single cycle assays and during spreading infections within cultures of peripheral blood mononuclear cells (PBMCs). To test the hypothesis that these AP-binding motifs target Env to endosomes during viral morphogenesis, we compared the subcellular localization of wild-type Env to mutants of the Y712 and LL855/856 signals. The results failed to support the hypothesis that these signals target viral assembly to specific endosomal membranes. Strikingly, in the context of a C2-V3 region that confers macrophage-tropism, mutation of Y712 no longer markedly affected viral infectivity in either single cycle assays or during spreading infection within PBMCs, and it did not impair viral entry. These data indicate that the importance of the tyrosine-based sorting signal in gp41 for optimal viral infectivity depends on sequences in gp120. This observation is consistent with the hypothesis that the Y712 residue is part of the ectodomain of gp41 in virion-associated Env. We speculate that as part of the ectodomain, Y712 could affect specifically the conformation of the more positively charged CXCR4-tropic V3 loop in a manner that augments viral fusogenicity and infectivity.

The effect of the membrane-proximal tyrosine-based sorting signal of HIV-1 gp41 on viral infectivity depends on sequences within gp120. Publishing Authors By Initials

JR Day,N Van Damme,JC Guatelli,

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The effect of the membrane-proximal tyrosine-based sorting signal of HIV-1 gp41 on viral infectivity depends on sequences within gp120. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Virology

VOLUME: 354

Page Numbers: 316-27

Journal Abbreviation: Virology

ISSN: 0042-6822

DAY: 14

MONTH: 08

YEAR: 2006

The effect of the membrane-proximal tyrosine-based sorting signal of HIV-1 gp41 on viral infectivity depends on sequences within gp120. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 110674

The effect of the membrane-proximal tyrosine-based sorting signal of HIV-1 gp41 on viral infectivity depends on sequences within gp120. Keywords Mesh Terms:

KEYWORDS: Virion

MESH TERMS: metabolism

Chemical & Substance for Abstract: The effect of the membrane-proximal tyrosine-based sorting signal of HIV-1 gp41 on viral infectivity depends on sequences within gp120. Information

Substance Name: Tyrosine

Registry Number: 55520-40-6

Grant and Affiliation Information for The effect of the membrane-proximal tyrosine-based sorting signal of HIV-1 gp41 on viral infectivity depends on sequences within gp120.

AFFILIATION: Department of Pathology, University of California San Diego, San Diego, CA, USA. johnday88@yahoo.com

Country: United States

AGENCY: United States NIAID

GRANT: AI36214

ACRONYM: AI

MEDLINETA: Virology

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