A Twin-Cysteine Motif in the V2 Region of gp120 Is Associated with SIV Envelope Trimer Stabilization

Authors

Christopher Bohl, University of Nebraska-Lincoln
Dane Bowder, University of Nebraska-Lincoln
Jesse Thompson, University of Nebraska-Lincoln
Levon Abrahamyan, University of Nebraska-Lincoln
Sandra Gonzalez-Ramirez, University of Nebraska-LincolnFollow
Youdong Mao, Dana-Farber Cancer Institute
Joseph Sodroski, Harvard Medical SchoolFollow
Charles Wood, University of Nebraska-LincolnFollow
Shi-Hua Xiang, University of Nebraska-LincolnFollow

Date of this Version

2013

Citation

Bohl C, Bowder D, Thompson J, Abrahamyan L, Gonzalez-Ramirez S, et al. (2013) A Twin-Cysteine Motif in the V2 Region of gp120 Is Associated with SIV Envelope Trimer Stabilization. PLoS ONE 8(7): e69406. doi:10.1371/journal.pone.0069406

Abstract

The V1 and V2 variable regions of the primate immunodeficiency viruses contribute to the trimer association domain of the gp120 exterior envelope glycoprotein. A pair of V2 cysteine residues at 183 and 191 (‘‘twin cysteines’’) is present in several simian immunodeficiency viruses, human immunodeficiency virus type 2 (HIV-2) and some SIV_cpz lineages, but not in HIV-1. To examine the role of this potentially disulfide-bonded twin-cysteine motif, the cysteine residues in the SIVmac239 envelope glycoproteins were individually and pairwise substituted by alanine residues. All of the twin-cysteine mutants exhibited decreases in gp120 association with the Env trimer, membrane-fusing activity, and ability to support virus entry. Thus, the twin-cysteine motif plays a role in Env trimer stabilization in SIV and may do so in HIV-2 and some SIV_cpz as well. This implies that HIV-1 lost the twin-cysteines, and may have relatively unstable Env trimers compared to SIV and HIV-2.