HIV-1 entry into host cells is mediated by the interaction of the V3 loop of gp120 and coreceptors CCR5 or CXCR4 on host cell surfaces, with assistance of viral protein gp41 and cell receptor CD4. The coreceptor choice is associated with asymptomatic viral infection (CCR5) or progression to disease (CXCR4). Based on previous experimental and computational data and renewed thinking, we have formed the hypothesis that as the positive net charge of the V3 loop increases the coreceptor selection switches from CCR5 to CXCR4, with an intermediate net charge value denoting dual specificity. Given the sequence and structural variability of the V3 loop, we have performed: (i) electrostatic and statistical analysis of 5309 V3 loop sequences with known coreceptor use, derived from patient data, and (ii) structural analysis of two 100-ns molecular dynamics trajectories, in search for persistent physicochemical properties that may be responsible in mediating coreceptor selectivity.

Role of gp120 V3 loop charge in HIV-1 coreceptor selectivity

243rd National Meeting (2012)

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