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 α4β7 are associated with HIV-1...

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Published in:Clinical infectious diseases 2020-12, Vol.71 (11), p.e735-e743
Main Authors: Tokarev, Andrey, McKinnon, Lyle R, Pagliuzza, Amélie, Sivro, Aida, Omole, Tosin E, Kroon, Eugene, Chomchey, Nitiya, Phanuphak, Nittaya, Schuetz, Alexandra, Robb, Merlin L, Eller, Michael A, Ananworanich, Jintanat, Chomont, Nicolas, Bolton, Diane L
Format: Article
Language:English
Subjects:
CD4-Positive T-Lymphocytes
HIV Infections - drug therapy
HIV-1
Humans
Leukocytes, Mononuclear
Online Only
T-Lymphocyte Subsets
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Summary: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. We demonstrate that memory CD4+ T cells expressing high levels of integrin β7 are enriched in total and integrated HIV-1 DNA compared to β7negative cells, and that preferential targeting of β7high cells is associated with their activation status.
ISSN:1058-4838
1537-6591
DOI:10.1093/cid/ciaa497