Structural Dynamics of HIV-1 Envelope Gp120 Outer Domain with V3 Loop

Masaru Yokoyama, Satoshi Naganawa, Kazuhisa Yoshimura, Shuzo Matsushita and Hironori Sato

PLOS ONE, 2012, vol. 7, issue 5, 1-9

Abstract: Background: The net charge of the hypervariable V3 loop on the HIV-1 envelope gp120 outer domain plays a key role in modulating viral phenotype. However, the molecular mechanisms underlying the modulation remain poorly understood. Methodology/Principal Findings: By combining computational and experimental approaches, we examined how V3 net charge could influence the phenotype of the gp120 interaction surface. Molecular dynamics simulations of the identical gp120 outer domain, carrying a V3 loop with net charge of +3 or +7, showed that the V3 change alone could induce global changes in fluctuation and conformation of the loops involved in binding to CD4, coreceptor and antibodies. A neutralization study using the V3 recombinant HIV-1 infectious clones showed that the virus carrying the gp120 with +3 V3, but not with +7 V3, was resistant to neutralization by anti-CD4 binding site monoclonal antibodies. An information entropy study shows that otherwise variable surface of the gp120 outer domain, such as V3 and a region around the CD4 binding loop, are less heterogeneous in the gp120 subpopulation with +3 V3. Conclusions/Significance: These results suggest that the HIV-1 gp120 V3 loop acts as an electrostatic modulator that influences the global structure and diversity of the interaction surface of the gp120 outer domain. Our findings will provide a novel structural basis to understand how HIV-1 adjusts relative replication fitness by V3 mutations.

Date: 2012
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0037530

DOI: 10.1371/journal.pone.0037530

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