Contribution of the gp120 V3 loop to envelope glycoprotein trimer stability in primate immunodeficiency viruses

Authors

Dane Bowder, University of Nebraska-LincolnFollow
Haley Hollingsead, University of Nebraska-Lincoln
Kate Durst, University of Nebraska-Lincoln
Duoyi Hu, University of Nebraska-Lincoln
Wenzhong Wei, University of Nebraska-Lincoln
Joshua Wiggins, University of Nebraska-LincolnFollow
Halima Medjahed, Universite de Montreal
Andrés Finzi, Universite de MontrealFollow
Joseph Sodroski, Dana-Farber Cancer InstituteFollow
Shi-Hua Xiang, University of Nebraska-LincolnFollow

Date of this Version

2018

Citation

Virology 521 (2018) 158–168

Comments

© 2018 The Authors

Open access

https://doi.org/10.1016/j.virol.2018.06.005

Abstract

The V3 loop of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein (Env) becomes exposed after CD4 binding and contacts the coreceptor to mediate viral entry. Prior to CD4 engagement, a hydrophobic patch located at the tip of the V3 loop stabilizes the non-covalent association of gp120 with the Env trimer of HIV-1 subtype B strains. Here, we show that this conserved hydrophobic patch (amino acid residues 307, 309 and 317) contributes to gp120-trimer association in HIV-1 subtype C, HIV-2 and SIV. Changes that reduced the hydrophobicity of these V3 residues resulted in increased gp120 shedding and decreased Envmediated cell-cell fusion and virus entry in the different primate immunodeficiency viruses tested. Thus, the hydrophobic patch is an evolutionarily conserved element in the tip of the gp120 V3 loop that plays an essential role in maintaining the stability of the pre-triggered Env trimer in diverse primate immunodeficiency viruses.