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Quantifying Susceptibility of CD4+ Stem Memory T-Cells to Infection by Laboratory Adapted and Clinical HIV-1 Strains

Center for Biomedical Research, Burnet Institute, Melbourne, Victoria 3004, Australia
Department of Infectious Diseases, Monash University, Melbourne, Victoria 3004, Australia
Alfred Medical Research and Education Precinct and Burnet Institute Flow Cytometry Core Facility, Melbourne, Victoria 3004, Australia
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia
Department of Microbiology, La Trobe University, Melbourne, Victoria 3086, Australia
Department of Biomedicine, Aarhus University, Aarhus 237551, Denmark
Department of Medicine, Monash University, Melbourne, Victoria 3004, Australia
Department of Microbiology, Monash University, Melbourne, Victoria 3010, Australia
Author to whom correspondence should be addressed.
Viruses 2014, 6(2), 709-726;
Received: 20 December 2013 / Revised: 5 February 2014 / Accepted: 6 February 2014 / Published: 10 February 2014
(This article belongs to the Special Issue HIV Latency)
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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. View Full-Text
Keywords: HIV-1; stem memory T cells; CD4+ T cells; T cell subsets; envelope; viral reservoir HIV-1; stem memory T cells; CD4+ T cells; T cell subsets; envelope; viral reservoir

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Flynn, J.K.; Paukovics, G.; Cashin, K.; Borm, K.; Ellett, A.; Roche, M.; Jakobsen, M.R.; Churchill, M.J.; Gorry, P.R. Quantifying Susceptibility of CD4+ Stem Memory T-Cells to Infection by Laboratory Adapted and Clinical HIV-1 Strains. Viruses 2014, 6, 709-726.

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