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CD25+ FoxP3+ Memory CD4 T Cells Are Frequent Targets of HIV Infection In Vivo.

Identifieur interne : 000378 ( PubMed/Corpus ); précédent : 000377; suivant : 000379

CD25+ FoxP3+ Memory CD4 T Cells Are Frequent Targets of HIV Infection In Vivo.

Auteurs : Mkunde Chachage ; Georgios Pollakis ; Edmund Osei Kuffour ; Kerstin Haase ; Asli Bauer ; Yuka Nadai ; Lilli Podola ; Petra Clowes ; Matthias Schiemann ; Lynette Henkel ; Dieter Hoffmann ; Sarah Joseph ; Sabin Bhuju ; Leonard Maboko ; Fred Stephen Sarfo ; Kirsten Eberhardt ; Michael Hoelscher ; Torsten Feldt ; Elmar Saathoff ; Christof Geldmacher

Source :

RBID : pubmed:27384654

English descriptors

Abstract

Interleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replication in vitro and facilitates homeostatic proliferation of CD25(+) FoxP3(+) CD4(+) T cells. CD25(+) FoxP3(+) CD4(+) T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25(+) FoxP3(+) CD4(+) T cell frequencies, absolute numbers, and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV(+) and HIV(-) study volunteers. Different memory CD4(+) T cell subsets were then sorted for quantification of cell-associated HIV DNA and phylogenetic analyses of the highly variable EnvV1V3 region in comparison to plasma-derived virus sequences. In HIV(+) subjects, 51% (median) of CD25(+) FoxP3(+) CD4(+) T cells expressed the HIV coreceptor CCR5. Very high frequencies of Ki67(+) cells were detected in CD25(+) FoxP3(+) memory CD4(+) T cells (median, 27.6%) in comparison to CD25(-) FoxP3(-) memory CD4(+) T cells (median, 4.1%; P < 0.0001). HIV DNA content was 15-fold higher in CD25(+) FoxP3(+) memory CD4(+) T cells than in CD25(-) FoxP3(-) T cells (P = 0.003). EnvV1V3 sequences derived from CD25(+) FoxP3(+) memory CD4(+) T cells did not preferentially cluster with plasma-derived sequences. Quasi-identical cell-plasma sequence pairs were rare, and their proportion decreased with the estimated HIV infection duration. These data suggest that specific cellular characteristics of CD25(+) FoxP3(+) memory CD4(+) T cells might facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. The contribution of this cell population to plasma virion production remains unclear.

DOI: 10.1128/JVI.00612-16
PubMed: 27384654

Links to Exploration step

pubmed:27384654

Le document en format XML

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<name sortKey="Hoffmann, Dieter" sort="Hoffmann, Dieter" uniqKey="Hoffmann D" first="Dieter" last="Hoffmann">Dieter Hoffmann</name>
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<name sortKey="Joseph, Sarah" sort="Joseph, Sarah" uniqKey="Joseph S" first="Sarah" last="Joseph">Sarah Joseph</name>
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<name sortKey="Sarfo, Fred Stephen" sort="Sarfo, Fred Stephen" uniqKey="Sarfo F" first="Fred Stephen" last="Sarfo">Fred Stephen Sarfo</name>
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<name sortKey="Saathoff, Elmar" sort="Saathoff, Elmar" uniqKey="Saathoff E" first="Elmar" last="Saathoff">Elmar Saathoff</name>
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<nlm:affiliation>Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.</nlm:affiliation>
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<nlm:affiliation>Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany mchachage@nimr-mmrc.org geldmacher@lrz.uni-muenchen.de.</nlm:affiliation>
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<term>CD4-Positive T-Lymphocytes (virology)</term>
<term>DNA, Viral (analysis)</term>
<term>DNA, Viral (genetics)</term>
<term>Forkhead Transcription Factors (analysis)</term>
<term>HIV (classification)</term>
<term>HIV (genetics)</term>
<term>HIV (isolation & purification)</term>
<term>HIV Infections (virology)</term>
<term>Humans</term>
<term>Interleukin-2 Receptor alpha Subunit (analysis)</term>
<term>Ki-67 Antigen (analysis)</term>
<term>Phylogeny</term>
<term>Receptors, CCR5 (analysis)</term>
<term>Sequence Analysis, DNA</term>
<term>T-Lymphocyte Subsets (chemistry)</term>
<term>T-Lymphocyte Subsets (virology)</term>
<term>env Gene Products, Human Immunodeficiency Virus (genetics)</term>
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<term>DNA, Viral</term>
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<term>Ki-67 Antigen</term>
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<term>CD4-Positive T-Lymphocytes</term>
<term>T-Lymphocyte Subsets</term>
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<term>T-Lymphocyte Subsets</term>
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<front>
<div type="abstract" xml:lang="en">Interleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replication in vitro and facilitates homeostatic proliferation of CD25(+) FoxP3(+) CD4(+) T cells. CD25(+) FoxP3(+) CD4(+) T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25(+) FoxP3(+) CD4(+) T cell frequencies, absolute numbers, and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV(+) and HIV(-) study volunteers. Different memory CD4(+) T cell subsets were then sorted for quantification of cell-associated HIV DNA and phylogenetic analyses of the highly variable EnvV1V3 region in comparison to plasma-derived virus sequences. In HIV(+) subjects, 51% (median) of CD25(+) FoxP3(+) CD4(+) T cells expressed the HIV coreceptor CCR5. Very high frequencies of Ki67(+) cells were detected in CD25(+) FoxP3(+) memory CD4(+) T cells (median, 27.6%) in comparison to CD25(-) FoxP3(-) memory CD4(+) T cells (median, 4.1%; P < 0.0001). HIV DNA content was 15-fold higher in CD25(+) FoxP3(+) memory CD4(+) T cells than in CD25(-) FoxP3(-) T cells (P = 0.003). EnvV1V3 sequences derived from CD25(+) FoxP3(+) memory CD4(+) T cells did not preferentially cluster with plasma-derived sequences. Quasi-identical cell-plasma sequence pairs were rare, and their proportion decreased with the estimated HIV infection duration. These data suggest that specific cellular characteristics of CD25(+) FoxP3(+) memory CD4(+) T cells might facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. The contribution of this cell population to plasma virion production remains unclear.</div>
</front>
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<PMID Version="1">27384654</PMID>
<DateCreated>
<Year>2016</Year>
<Month>09</Month>
<Day>30</Day>
</DateCreated>
<DateCompleted>
<Year>2017</Year>
<Month>05</Month>
<Day>10</Day>
</DateCompleted>
<DateRevised>
<Year>2017</Year>
<Month>05</Month>
<Day>10</Day>
</DateRevised>
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<Journal>
<ISSN IssnType="Electronic">1098-5514</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>90</Volume>
<Issue>20</Issue>
<PubDate>
<Year>2016</Year>
<Month>Oct</Month>
<Day>15</Day>
</PubDate>
</JournalIssue>
<Title>Journal of virology</Title>
<ISOAbbreviation>J. Virol.</ISOAbbreviation>
</Journal>
<ArticleTitle>CD25+ FoxP3+ Memory CD4 T Cells Are Frequent Targets of HIV Infection In Vivo.</ArticleTitle>
<Pagination>
<MedlinePgn>8954-67</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1128/JVI.00612-16</ELocationID>
<Abstract>
<AbstractText Label="UNLABELLED">Interleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replication in vitro and facilitates homeostatic proliferation of CD25(+) FoxP3(+) CD4(+) T cells. CD25(+) FoxP3(+) CD4(+) T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25(+) FoxP3(+) CD4(+) T cell frequencies, absolute numbers, and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV(+) and HIV(-) study volunteers. Different memory CD4(+) T cell subsets were then sorted for quantification of cell-associated HIV DNA and phylogenetic analyses of the highly variable EnvV1V3 region in comparison to plasma-derived virus sequences. In HIV(+) subjects, 51% (median) of CD25(+) FoxP3(+) CD4(+) T cells expressed the HIV coreceptor CCR5. Very high frequencies of Ki67(+) cells were detected in CD25(+) FoxP3(+) memory CD4(+) T cells (median, 27.6%) in comparison to CD25(-) FoxP3(-) memory CD4(+) T cells (median, 4.1%; P < 0.0001). HIV DNA content was 15-fold higher in CD25(+) FoxP3(+) memory CD4(+) T cells than in CD25(-) FoxP3(-) T cells (P = 0.003). EnvV1V3 sequences derived from CD25(+) FoxP3(+) memory CD4(+) T cells did not preferentially cluster with plasma-derived sequences. Quasi-identical cell-plasma sequence pairs were rare, and their proportion decreased with the estimated HIV infection duration. These data suggest that specific cellular characteristics of CD25(+) FoxP3(+) memory CD4(+) T cells might facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. The contribution of this cell population to plasma virion production remains unclear.</AbstractText>
<AbstractText Label="IMPORTANCE" NlmCategory="OBJECTIVE">Despite recent advances in the understanding of AIDS virus pathogenesis, which cell subsets support HIV infection and replication in vivo is incompletely understood. In vitro, the IL-2 signaling pathway and IL-2-dependent cell cycle induction are essential for HIV infection of stimulated T cells. CD25(+) FoxP3(+) memory CD4 T cells, often referred to as regulatory CD4 T cells, depend on IL-2 signaling for homeostatic proliferation in vivo Our results show that CD25(+) FoxP3(+) memory CD4(+) T cells often express the HIV coreceptor CCR5, are significantly more proliferative, and contain more HIV DNA than CD25(-) FoxP3(-) memory CD4 T cell subsets. The specific cellular characteristics of CD25(+) FoxP3(+) memory CD4(+) T cells probably facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. However, the contribution of this cell subset to plasma viremia remains unclear.</AbstractText>
<CopyrightInformation>Copyright © 2016, American Society for Microbiology. All Rights Reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Chachage</LastName>
<ForeName>Mkunde</ForeName>
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