Preferential Infection of α4β7+ Memory CD4+ T Cells During Early Acute Human Immunodeficiency Virus Type 1 Infection
Andrey Tokarev, Lyle R. McKinnon, Amélie Pagliuzza, Aida Sivro, Tosin Omole, Eugène Kroon, Nitiya Chomchey, Nittaya Phanuphak, Alexandra Schuetz, Merlin L. Robb, Michael A. Eller, Jintanat Ananworanich, Nicolas Chomont, Diane L. Bolton
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 α4β7 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 β7 (β7negative and β7high, 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 β7-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 β7high and β7negative subsets, with no significant difference in HIV-1 DNA copies. In Fiebig stages II/III and in chronically infected individuals, β7high cells were enriched in integrated and total HIV-1 DNA compared to β7negative cells. During suppressive cART, integrated HIV-1 DNA copies decreased in both β7negative and β7high subsets, which did not differ in DNA copies. In Fiebig II/III, integrated HIV-1 DNA in β7high cells was correlated with their activation. CONCLUSIONS: β7high memory CD4+ T cells are preferential targets during early HIV-1 infection, which may be due to the increased activation of these cells.