CD4+ T cells from elite suppressors are more susceptible to HIV-1 but produce fewer virions than cells from chronic progressors.

Abstract

Elite suppressors/controllers (ES) are HIV-1-infected individuals who maintain stable CD4(+) T-cell counts and viral loads of <50 copies/mL without antiretroviral therapy. Research has predominantly focused on immune factors contributing to the control of viral replication in these patients. A more fundamental question, however, is whether there are differences in the nature of CD4(+) T-cell infection in ES compared with viremic patients. Here, we compare chronic progressor (CP), ES, and uninfected donors in terms of three aspects of CD4(+) T-cell infection: cellular susceptibility to infection, death of infected cells, and production of virus from infected cells. Using multiple methods of infection and both single-cycle and replication-competent virus, we show that unmanipulated CD4(+) T-cell populations from ES are actually more susceptible to HIV-1 infection than those populations from CP. Depletion of highly susceptible cells in CP may contribute to this difference. Using 7AAD and AnnexinV staining, we show that infected cells die more rapidly than uninfected cells, but the increased death of infected cells from CP and ES is proportional. Finally, using an assay for measuring virus production, we show that virus production by cells from CP is high compared with virus production by cells from ES or uninfected donors. This higher virus production is linked to cellular activation levels. These data identify fundamental differences in chronic infection of ES and CP that likely contribute to differential HIV-1 disease progression.