1. Contribution of the gp120 V3 loop to envelope glycoprotein trimer stability in primate immunodeficiency viruses
- Author
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Bowder, Dane, Hollingsead, Haley, Durst, Kate, Hu, Duoyi, Wei, Wenzhong, Wiggins, Joshua, Medjahed, Halima, Finzi, Andrés, Sodroski, Joseph, and Xiang, Shi-Hua
- Subjects
Membrane Glycoproteins ,Protein Stability ,viruses ,Hydrophobic patch ,virus diseases ,HIV Envelope Protein gp120 ,Virus Internalization ,Article ,gp120 ,HEK293 Cells ,Viral Envelope Proteins ,HIV-2 ,Simian immunodeficiency virus (SIV) ,HIV-1 ,V3 loop ,Humans ,Simian Immunodeficiency Virus ,Protein Multimerization ,Hydrophobic and Hydrophilic Interactions ,Primate immunodeficiency viruses (PIV) - 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 Env-mediated 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., Highlights • The V3-loop of HIV-1 gp120 contributes to Env trimer stability and viral entry. • The hydrophobic patch in the tip of the V3 loop is critical for pre-triggered Env trimer stability. • The hydrophobic patch is a conserved motif in primate immunodeficiency viruses.
- Published
- 2018