HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells.
Identifieur interne : 000D45 ( PubMed/Corpus ); précédent : 000D44; suivant : 000D46HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells.
Auteurs : Yin Xu ; Chansavath Phetsouphanh ; Kazuo Suzuki ; Anu Aggrawal ; Stephanie Graff-Dubois ; Michael Roche ; Michelle Bailey ; Sheilajen Alcantara ; Kieran Cashin ; Rahuram Sivasubramaniam ; Kersten K. Koelsch ; Brigitte Autran ; Richard Harvey ; Paul R. Gorry ; Arnaud Moris ; David A. Cooper ; Stuart Turville ; Stephen J. Kent ; Anthony D. Kelleher ; John ZaundersSource :
- Frontiers in immunology [ 1664-3224 ] ; 2017.
Abstract
T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4(+) T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells.
DOI: 10.3389/fimmu.2017.00376
PubMed: 28484447
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pubmed:28484447Le document en format XML
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<author><name sortKey="Turville, Stuart" sort="Turville, Stuart" uniqKey="Turville S" first="Stuart" last="Turville">Stuart Turville</name>
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<author><name sortKey="Kelleher, Anthony D" sort="Kelleher, Anthony D" uniqKey="Kelleher A" first="Anthony D" last="Kelleher">Anthony D. Kelleher</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells.</title>
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<author><name sortKey="Phetsouphanh, Chansavath" sort="Phetsouphanh, Chansavath" uniqKey="Phetsouphanh C" first="Chansavath" last="Phetsouphanh">Chansavath Phetsouphanh</name>
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</affiliation>
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<author><name sortKey="Suzuki, Kazuo" sort="Suzuki, Kazuo" uniqKey="Suzuki K" first="Kazuo" last="Suzuki">Kazuo Suzuki</name>
<affiliation><nlm:affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</nlm:affiliation>
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<author><name sortKey="Aggrawal, Anu" sort="Aggrawal, Anu" uniqKey="Aggrawal A" first="Anu" last="Aggrawal">Anu Aggrawal</name>
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</affiliation>
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<author><name sortKey="Graff Dubois, Stephanie" sort="Graff Dubois, Stephanie" uniqKey="Graff Dubois S" first="Stephanie" last="Graff-Dubois">Stephanie Graff-Dubois</name>
<affiliation><nlm:affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Roche, Michael" sort="Roche, Michael" uniqKey="Roche M" first="Michael" last="Roche">Michael Roche</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia.</nlm:affiliation>
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<author><name sortKey="Bailey, Michelle" sort="Bailey, Michelle" uniqKey="Bailey M" first="Michelle" last="Bailey">Michelle Bailey</name>
<affiliation><nlm:affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Alcantara, Sheilajen" sort="Alcantara, Sheilajen" uniqKey="Alcantara S" first="Sheilajen" last="Alcantara">Sheilajen Alcantara</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Cashin, Kieran" sort="Cashin, Kieran" uniqKey="Cashin K" first="Kieran" last="Cashin">Kieran Cashin</name>
<affiliation><nlm:affiliation>Center for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Sivasubramaniam, Rahuram" sort="Sivasubramaniam, Rahuram" uniqKey="Sivasubramaniam R" first="Rahuram" last="Sivasubramaniam">Rahuram Sivasubramaniam</name>
<affiliation><nlm:affiliation>St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Koelsch, Kersten K" sort="Koelsch, Kersten K" uniqKey="Koelsch K" first="Kersten K" last="Koelsch">Kersten K. Koelsch</name>
<affiliation><nlm:affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</nlm:affiliation>
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<author><name sortKey="Autran, Brigitte" sort="Autran, Brigitte" uniqKey="Autran B" first="Brigitte" last="Autran">Brigitte Autran</name>
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</affiliation>
</author>
<author><name sortKey="Harvey, Richard" sort="Harvey, Richard" uniqKey="Harvey R" first="Richard" last="Harvey">Richard Harvey</name>
<affiliation><nlm:affiliation>St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW, Australia.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Gorry, Paul R" sort="Gorry, Paul R" uniqKey="Gorry P" first="Paul R" last="Gorry">Paul R. Gorry</name>
<affiliation><nlm:affiliation>Center for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Moris, Arnaud" sort="Moris, Arnaud" uniqKey="Moris A" first="Arnaud" last="Moris">Arnaud Moris</name>
<affiliation><nlm:affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Cooper, David A" sort="Cooper, David A" uniqKey="Cooper D" first="David A" last="Cooper">David A. Cooper</name>
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</affiliation>
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</affiliation>
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<author><name sortKey="Kent, Stephen J" sort="Kent, Stephen J" uniqKey="Kent S" first="Stephen J" last="Kent">Stephen J. Kent</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kelleher, Anthony D" sort="Kelleher, Anthony D" uniqKey="Kelleher A" first="Anthony D" last="Kelleher">Anthony D. Kelleher</name>
<affiliation><nlm:affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Zaunders, John" sort="Zaunders, John" uniqKey="Zaunders J" first="John" last="Zaunders">John Zaunders</name>
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</affiliation>
</author>
</analytic>
<series><title level="j">Frontiers in immunology</title>
<idno type="ISSN">1664-3224</idno>
<imprint><date when="2017" type="published">2017</date>
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<front><div type="abstract" xml:lang="en">T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4(+) T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">28484447</PMID>
<DateCreated><Year>2017</Year>
<Month>05</Month>
<Day>09</Day>
</DateCreated>
<DateRevised><Year>2017</Year>
<Month>08</Month>
<Day>16</Day>
</DateRevised>
<Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">1664-3224</ISSN>
<JournalIssue CitedMedium="Print"><Volume>8</Volume>
<PubDate><Year>2017</Year>
</PubDate>
</JournalIssue>
<Title>Frontiers in immunology</Title>
<ISOAbbreviation>Front Immunol</ISOAbbreviation>
</Journal>
<ArticleTitle>HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells.</ArticleTitle>
<Pagination><MedlinePgn>376</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.3389/fimmu.2017.00376</ELocationID>
<Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4(+) T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells.</AbstractText>
<AbstractText Label="METHODOLOGY" NlmCategory="METHODS">Tfh and other CD4(+) T cell subsets from macaque lymph nodes and spleens, splenic Tfh from HIV(+) subjects, and tonsillar Tfh from HIV-uninfected subjects were isolated by cell sorting prior to cell surface and molecular characterization. HIV proviral gp120 sequences were submitted to genotypic and phenotypic tropism assays. Entry of CCR5- and CXCR4-using viruses into Tfh from uninfected tonsillar tissue was measured using a fusion assay.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">Phylogenetic analysis, genotypic, and phenotypic analysis showed that splenic Tfh cells from chronic HIV(+) subjects were predominantly infected with CCR5-using viruses. In macaques, purified CCR5(+)PD-1(intermediate(int)+) memory CD4(+) T cells were shown to include pre-Tfh cells capable of differentiating in vitro to Tfh by upregulation of PD-1 and Bcl6, confirmed by qRT-PCR and single-cell multiplex PCR. Infected PD-1(int) cells survive, carry SIV provirus, and differentiate into PD-1(hi) Tfh after T cell receptor stimulation, suggesting a pathway for SIV infection of Tfh. In addition, a small subset of macaque and human PD-1(hi) Tfh can express low levels of CCR5, which makes them susceptible to infection. Fusion assays demonstrated CCR5-using HIV-1 entry into CCR5(+) Tfh and pre-Tfh cells from human tonsils.</AbstractText>
<AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">The major route of infection of Tfh in macaques and humans appears to be via a CCR5-expressing pre-Tfh population. As the generation of Tfh are important for establishing effective immune responses during primary infections, Tfh are likely to be an early target of HIV-1 following transmission, creating an important component of the reservoir that has the potential to expand over time.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Xu</LastName>
<ForeName>Yin</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Phetsouphanh</LastName>
<ForeName>Chansavath</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Suzuki</LastName>
<ForeName>Kazuo</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Aggrawal</LastName>
<ForeName>Anu</ForeName>
<Initials>A</Initials>
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</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Graff-Dubois</LastName>
<ForeName>Stephanie</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Roche</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Center for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bailey</LastName>
<ForeName>Michelle</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Alcantara</LastName>
<ForeName>Sheilajen</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cashin</LastName>
<ForeName>Kieran</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Center for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sivasubramaniam</LastName>
<ForeName>Rahuram</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Koelsch</LastName>
<ForeName>Kersten K</ForeName>
<Initials>KK</Initials>
<AffiliationInfo><Affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Autran</LastName>
<ForeName>Brigitte</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Sorbonne Universités, UPMC University Paris 06, INSERM U1135, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Harvey</LastName>
<ForeName>Richard</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gorry</LastName>
<ForeName>Paul R</ForeName>
<Initials>PR</Initials>
<AffiliationInfo><Affiliation>Center for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>School of Health and Biomedical Sciences, College of Science, Engineering and Health, RMIT University, Bundoora, VIC, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Moris</LastName>
<ForeName>Arnaud</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cooper</LastName>
<ForeName>David A</ForeName>
<Initials>DA</Initials>
<AffiliationInfo><Affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Turville</LastName>
<ForeName>Stuart</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kent</LastName>
<ForeName>Stephen J</ForeName>
<Initials>SJ</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Infectious Diseases, Alfred Hospital, Monash University, Melbourne, VIC, Australia.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Kelleher</LastName>
<ForeName>Anthony D</ForeName>
<Initials>AD</Initials>
<AffiliationInfo><Affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zaunders</LastName>
<ForeName>John</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
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<Language>eng</Language>
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<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">CCR5</Keyword>
<Keyword MajorTopicYN="N">CD4</Keyword>
<Keyword MajorTopicYN="N">HIV-1</Keyword>
<Keyword MajorTopicYN="N">T follicular helper cells</Keyword>
<Keyword MajorTopicYN="N">germinal center</Keyword>
</KeywordList>
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<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year>
<Month>10</Month>
<Day>08</Day>
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<PubMedPubDate PubStatus="accepted"><Year>2017</Year>
<Month>03</Month>
<Day>15</Day>
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