Structure/Function Studies Involving the V3 Region of the HIV-1 Envelope Delineate Multiple Factors That Affect Neutralization Sensitivity

• DOI: 10.1128/jvi.01645-15
• Publication Date: 2015-10-22T15:02:01Z
• Authors: Susan Zolla-Pazner; Sandra Sharpe Cohen; David Boyd; Xiang-Peng Kong; Michael Seaman; Michel Nussenzweig; Florian Klein; Julie Overbaugh; Max Totrov
• Keywords: Trimer; V3 loop; Viral protein; Envelope (radar)

Antibodies (Abs) specific for the V3 loop of HIV-1 gp120 envelope neutralize most tier 1 and many 2 viruses are present in essentially all HIV-infected individuals as well immunized humans animals. Vaccine-induced Abs associated with reduced HIV infection rates affect nature transmitted infected vaccinees, despite fact that is often occluded trimer. Here, we link structural experimental data showing how conformational alterations trimer render exceptionally sensitive to Abs. The experiments interrogated neutralization sensitivity pseudoviruses single amino acid mutations various regions were predicted alter packing Env results indicate metastable on virion surface, flickering between states which either or available binding chemokine receptors (leading infection) virus neutralization). spring-loaded easily released by disruption stability pocket unliganded favorable V3/pocket interactions. Formation requires appropriate positioning V1V2 domain, is, turn, dependent conformation bridging sheet B-C strand-connecting loop.