Preferential Infection of α4β7+ Memory CD4+ T Cells During Early Acute Human Immunodeficiency Virus Type 1 Infection. (29th April 2020)

• Record Type: Journal Article
• 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
• Is Part Of: Clinical infectious diseases. Volume 71:Number 11(2020)
• Page Start: e735
• Page End: e743
• Publication Date: 2020-04-29
• Subjects: HIV-1 -- acute infection -- integrin -- 7 -- activation; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa497
• Languages: English
• ISSNs: 1058-4838

Abstract

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 (β7 negative and β7 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 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 β7 high and β7 negative subsets, with no significant difference in HIV-1 DNA copies. In Fiebig stages II/III and in chronically infected individuals, β7 high cells were enriched in integrated and total HIV-1 DNA compared to β7 negative cells. During suppressive cART, integrated HIV-1 DNA copies decreased in both β7 negative and β7 high subsets, which did not differ in DNA copies. In Fiebig II/III, integrated HIV-1 DNA in β7 high cells was correlated with their activation. Conclusions: β7 high memory CD4 + T cells are preferential targets during early HIV-1 infection, which may be due to the increased activation of these cells. Abstract : We demonstrate that memory CD4 + T cells expressing high levels of integrin β7 are enriched in total and integrated HIV-1 DNA compared to β7 negative cells, and that preferential targeting of β7 high cells is associated with their activation status.