In vivo HIV-1 infection of CD45RA(+)CD4(+) T cells is established primarily by syncytium-inducing variants and correlates with the rate of CD4(+) T cell decline

Switch from non-syncytium-inducing (NSI) to syncytium-inducing (SI) HIV typ e 1 (HIV-1) is associated with accelerated CD4(+) T cell depletion, which m ight partially be explained by higher virulence of SI variants compared wit h NSI variants. Because NSI and SI variants use different coreceptors for e ntry of target cells, altered tropism might offer an explanation for increa sed pathogenesis associated with SI HIV-1 infection. To investigate whether SI and NSI HIV-1 variants infect different CD4(+) T cell subsets in vivo, the distribution of SI and NSI variants over CD4(+) memory (CD45RA(-)RO(+)) and naive (CD45RA(+)RO(-)) cells was studied by using limiting dilution cu ltures. In contrast to NSI variants that were mainly present in CD45RO(+) c ells, SI variants were equally distributed over CD45RO(+) and CD45RA(+) cel ls. Infection of memory cells by both NSI and SI HIV-1 and infection of nai ve cells primarily by SI HIV-1 corresponded closely with the differential c ell surface expression of CXCR4 and CCR5. The frequency of SI-infected CD45 RA(+) CD4(+) T cells, but not the frequency of NSI- or SI-infected CD45RO() CD4(+) T cells, correlated with the rate of CD4(+) T cell depletion. Infe ction of naive cells by SI HIV-1 may interfere with CD4(+) T cell productio n and thus account for rapid CD4(+) T cell depletion.