Preferential infection of alpha4beta7+ memory CD4+ T cells during early acute HIV-1 infection.

BACKGROUND: Establishment of persistent HIV-1 reservoirs occurs early in infection and biomarkers of infected CD4+ T cells during acute infection are poorly defined. CD4+ T cells expressing the gut homing integrin complex alpha4beta7 are associated with HIV-1 acquisition, and are rapidly depleted from the periphery and gastrointestinal mucosa during acute HIV-1 infection. METHODS: Integrated HIV-1 DNA was quantified in PBMC obtained from acutely (Fiebig I-III) and chronically infected individuals by sorting memory CD4+ T cell subsets lacking or expressing high levels of integrin beta7 (beta7negative and beta7high, respectively). HIV-1 DNA was also assessed after eight months of combination ART (cART) initiated in Fiebig II/III. Activation marker and chemokine receptor expression was determined for beta7-defined subsets at acute infection and in uninfected controls. RESULTS: In Fiebig I, memory CD4+ T cells harboring integrated HIV-1 DNA were rare in both beta7high and beta7negative subsets, with no significant difference in HIV-1 DNA copies. In Fiebig stages II/III and in chronically infected individuals, beta7high cells were enriched in integrated and total HIV-1 DNA compared to beta7negative cells. During suppressive cART, integrated HIV-1 DNA copies decreased in both beta7negative and beta7high subsets, which did not differ in DNA copies. In Fiebig II/III, integrated HIV-1 DNA in beta7high cells was correlated with their activation. CONCLUSIONS: beta7high memory CD4+ T cells are preferential targets during early HIV-1 infection, which may be due to the increased activation of these cells.