Stoichiometric parameters of HIV-1 entry

Abstract

During HIV type 1 (HIV-1) entry, trimers of gp120 bind to CD4 and either the CCR5 or CXCR4 coreceptor on the target cell. The stoichiometric parameters associated with HIV-1 entry remain unclear. Important unanswered questions include: how many trimers must attach to CD4 molecules, how many must bind coreceptors, and how many functional gp120 subunits per trimer are required for entry? We performed single round infectivity assays with chimeric viruses and compared the experimental relative infectivity curves with curves generated by mathematical models. Our results indicate that HIV-1 entry requires only a small number of functional spikes (one or two), that Env trimers may function with fewer than three active subunits, and that there is no major difference in the stoichiometric requirements for CCR5 vs. CXCR4 mediated HIV-1 entry into host cells.

Keywords: CCR5; CD4; CXCR4; Entry; Env; HIV-2; Relative infectivity; gp120.