Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops

Carlos G. Moscoso, Li Xing, Jinwen Hui, Jeffrey Hu, Mohammad Baikoghli Kalkhoran, Onur M. Yenigun, Yide Sun, Lassi Paavolainen, Loïc Martin, Anders Vahlne, Carlo Zambonelli, Susan W. Barnett, Indresh K. Srivastava, R. Holland Cheng

Research output: Contribution to journalArticle

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Abstract

Hypervariable loops of HIV-1 Env protein gp120 are speculated to play roles in the conformational transition of Env to the receptor binding-induced metastable state. Structural analysis of full-length Env-based immunogens, containing the entire V2 loop, displayed tighter association between gp120 subunits, resulting in a smaller trimeric diameter than constructs lacking V2. A prominent basal quaternary location of V2 and V39 that challenges previous reports would facilitate gp41-independent gp120-gp120 interactions and suggests a quaternary mechanism of epitope occlusion facilitated by hypervariable loops. Deletion of V2 resulted in dramatic exposure of basal, membrane-proximal gp41 epitopes, consistent with its predicted basal location. The structural features of HIV-1 Env characterized here provide grounds for a paradigm shift in loop exposure and epitope occlusion, while providing substantive rationale for epitope display required for elicitation of broadly neutralizing antibodies, as well as substantiating previous pertinent literature disregarded in recent reports.

Original languageEnglish (US)
Article number7025
JournalScientific Reports
Volume4
DOIs
StatePublished - Nov 14 2014

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Epitopes
HIV
HIV-1
HIV Envelope Protein gp120
Neutralizing Antibodies
Membranes

ASJC Scopus subject areas

  • General

Cite this

Moscoso, C. G., Xing, L., Hui, J., Hu, J., Kalkhoran, M. B., Yenigun, O. M., ... Cheng, R. H. (2014). Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops. Scientific Reports, 4, [7025]. https://doi.org/10.1038/srep07025

Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops. / Moscoso, Carlos G.; Xing, Li; Hui, Jinwen; Hu, Jeffrey; Kalkhoran, Mohammad Baikoghli; Yenigun, Onur M.; Sun, Yide; Paavolainen, Lassi; Martin, Loïc; Vahlne, Anders; Zambonelli, Carlo; Barnett, Susan W.; Srivastava, Indresh K.; Cheng, R. Holland.

In: Scientific Reports, Vol. 4, 7025, 14.11.2014.

Research output: Contribution to journalArticle

Moscoso, CG, Xing, L, Hui, J, Hu, J, Kalkhoran, MB, Yenigun, OM, Sun, Y, Paavolainen, L, Martin, L, Vahlne, A, Zambonelli, C, Barnett, SW, Srivastava, IK & Cheng, RH 2014, 'Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops', Scientific Reports, vol. 4, 7025. https://doi.org/10.1038/srep07025
Moscoso CG, Xing L, Hui J, Hu J, Kalkhoran MB, Yenigun OM et al. Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops. Scientific Reports. 2014 Nov 14;4. 7025. https://doi.org/10.1038/srep07025
Moscoso, Carlos G. ; Xing, Li ; Hui, Jinwen ; Hu, Jeffrey ; Kalkhoran, Mohammad Baikoghli ; Yenigun, Onur M. ; Sun, Yide ; Paavolainen, Lassi ; Martin, Loïc ; Vahlne, Anders ; Zambonelli, Carlo ; Barnett, Susan W. ; Srivastava, Indresh K. ; Cheng, R. Holland. / Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops. In: Scientific Reports. 2014 ; Vol. 4.
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