Preferential Infection of α4β7+ Memory CD4+ T Cells During Early Acute Human Immunodeficiency Virus Type 1 Infection

Clin Infect Dis. 2020 Dec 31;71(11):e735-e743. doi: 10.1093/cid/ciaa497.

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.

Keywords: 7; HIV-1; activation; acute infection; integrin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • CD4-Positive T-Lymphocytes
  • HIV Infections* / drug therapy
  • HIV-1*
  • Humans
  • Leukocytes, Mononuclear
  • T-Lymphocyte Subsets