title: The majority of HIV type 1 DNA in circulating CD4+ T lymphocytes is present in non-gut-homing resting memory CD4+ T cells.
abstract: Memory CD4(+) T lymphocytes in peripheral blood that express integrins α4ß7 preferentially recirculate through gut-associated lymphoid tissue (GALT), a proposed site of significant HIV-1 replication. Tregs and activated CD4(+) T cells in GALT could also be particularly susceptible to infection. We therefore hypothesized that infection of these subsets of memory CD4(+) T cells may contribute disproportionately to the HIV-1 reservoir. A cross-sectional study of CD4(+) T cell subsets of memory CD45RO(+) cells in peripheral blood mononuclear cells (PBMCs) was conducted using leukapheresis from eight subjects with untreated chronic HIV-1 infection. Real-time polymerase chain reaction (PCR) was used to quantify total and integrated HIV-1 DNA levels from memory CD4(+) T cells sorted into integrin β7(+) vs. β7(-), CD25(+)CD127(low) Treg vs. CD127(high), and activated CD38(+) vs. CD38(-). More than 80% of total HIV-1 DNA was found to reside in the integrin β7-negative non-gut-homing subset of CD45RO(+) memory CD4(+) T cells. Less than 10% was found in highly purified Tregs or CD38(+) activated memory cells. Similarly, integrated HIV-1 DNA copies were found to be more abundant in resting non-gut-homing memory CD4(+) T cells (76%) than in their activated counterparts (23%). Our investigations showed that the majority of both total and integrated HIV-1 DNA was found within non-gut-homing resting CD4(+) T cells.
authors: 1 The Kirby Institute for Infection and Immunity in Society, University of New South Wales , Sydney, Australia .
authors: Kristin
authors: K
authors: McBride
authors: Yin
authors: Y
authors: Xu
authors: Michelle
authors: M
authors: Bailey
authors: Nabila
authors: N
authors: Seddiki
authors: Kazuo
authors: K
authors: Suzuki
authors: John M
authors: JM
authors: Murray
authors: Yuan
authors: Y
authors: Gao
authors: Celine
authors: C
authors: Yan
authors: David A
authors: DA
authors: Cooper
authors: Anthony D
authors: AD
authors: Kelleher
authors: Kersten K
authors: KK
authors: Koelsch
authors: John
authors: J
authors: Zaunders
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000821:virology*; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D039641:Integrin beta Chains / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000821:virology; D008297:Male; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000821:virology*
chemical_list: D015703:Antigens, CD; D004279:DNA, Viral; D039641:Integrin beta Chains
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