quantifying susceptibility of cd4+ stem memory t-cells to infection by laboratory adapted and clinical hiv-1 strains

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2014
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Abstract
CD4+ T cells are principal targets for human immunodeficiency virus type 1 (HIV-1) infection. CD4+ T cell subsets are heterogeneous cell populations, divided by functional and phenotypic differences into naïve and memory T cells. The memory CD4+ T cells are further segregated into central, effector and transitional memory cell subsets by functional, phenotypic and homeostatic characteristics. Defining the distribution of HIV-1 infection in different T cell subsets is important, as this can play a role in determining the size and composition of the viral reservoir. Both central memory and transitional memory CD4+ T cells have been described as long-lived viral reservoirs for HIV. Recently, the newly described stem memory T cell subset has also been implicated as a long-lived HIV reservoir. Using green fluorescent protein (GFP) reporter strains of HIV-1 and multi parameter flow cytometry, we developed an assay to simultaneously quantify the susceptibility of stem memory (TSCM), central memory, effector memory, transitional memory and naïve CD4+ T cell subsets, to HIV-1 infection in vitro. We show that TSCM are susceptible to infection with laboratory adapted and clinical HIV-1 strains. Our system facilitates the quantitation of HIV-1 infection in alternative T cell subsets by CCR5- and CXCR4-using viruses across different HIV-1 subtypes, and will be useful for studies of HIV-1 pathogenesis and viral reservoirs.
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Authors Jacqueline K. Flynn, Geza Paukovics, Kieran Cashin, Katharina Borm, Anne Ellett, Michael Roche, Martin R. Jakobsen, Melissa J. Churchill, Paul R. Gorry
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Journal International journal of pharmaceutics
Year 2014
DOI
10.3390/v6020709
URL
http://www.mdpi.com/1999-4915/6/2/709
Keywords
hiv-1 envelope cd4+ t cells viral reservoirmicrobiology

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