Preferential Infection of α4β7+ 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 alpha 4 beta 7 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 beta 7 (beta 7(negative) and beta 7(high), 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 beta 7-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 beta 7(high) and beta 7(negative) subsets, with no significant difference in HIV-1 DNA copies. In Fiebig stages II/III and in chronically infected individuals, beta 7(high) cells were enriched in integrated and total HIV-1 DNA compared to beta 7(negative) cells. During suppressive cART, integrated HIV-1 DNA copies decreased in both beta 7(negative) and beta 7(high) subsets, which did not differ in DNA copies. In Fiebig II/III, integrated HIV-1 DNA in beta 7(high) cells was correlated with their activation. Conclusions. beta 7(high) memory CD4(+) T cells are preferential targets during early HIV-1 infection, which may be due to the increased activation of these cells.