Preferential Infection of α4ß7+ Memory CD4+ T Cells During Early Acute Human Immunodeficiency Virus Type 1 Infection.

ABSTRACT

BACKGROUND: Establishment of persistent human immunodeficiency virus type 1 (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 α4ß7 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 peripheral blood mononuclear cells obtained from acutely (Fiebig I-III) and chronically infected individuals by sorting memory CD4+ T-cell subsets lacking or expressing high levels of integrin ß7 (ß7negative and ß7high, respectively). HIV-1 DNA was also assessed after 8 months of combination antiretroviral therapy (cART) initiated in Fiebig II/III individuals. Activation marker and chemokine receptor expression was determined for ß7-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 ß7high and ß7negative subsets, with no significant difference in HIV-1 DNA copies. In Fiebig stages II/III and in chronically infected individuals, ß7high cells were enriched in integrated and total HIV-1 DNA compared to ß7negative cells. During suppressive cART, integrated HIV-1 DNA copies decreased in both ß7negative and ß7high subsets, which did not differ in DNA copies. In Fiebig II/III, integrated HIV-1 DNA in ß7high cells was correlated with their activation. CONCLUSIONS: ß7high memory CD4+ T cells are preferential targets during early HIV-1 infection, which may be due to the increased activation of these cells.