Chemokine receptor expression in the human ectocervix: implications for infection by the human immunodeficiency virus‐type I

Summary Human immunodeficiency virus‐type 1 (HIV‐1) is a sexually transmitted pathogen that can infect cells in the female reproductive tract (FRT). The mechanism of viral transmission within the FRT and the mode of viral spread to the periphery are not well understood. To characterize the frequency...

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Veröffentlicht in:Immunology 2004-12, Vol.113 (4), p.524-533
Hauptverfasser: Yeaman, Grant R., Asin, Susana, Weldon, Sally, Demian, Douglas J., Collins, Jane E., Gonzalez, Jorge L., Wira, Charles R., Fanger, Michael W., Howell, Alexandra L.
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container_end_page 533
container_issue 4
container_start_page 524
container_title Immunology
container_volume 113
creator Yeaman, Grant R.
Asin, Susana
Weldon, Sally
Demian, Douglas J.
Collins, Jane E.
Gonzalez, Jorge L.
Wira, Charles R.
Fanger, Michael W.
Howell, Alexandra L.
description Summary Human immunodeficiency virus‐type 1 (HIV‐1) is a sexually transmitted pathogen that can infect cells in the female reproductive tract (FRT). The mechanism of viral transmission within the FRT and the mode of viral spread to the periphery are not well understood. To characterize the frequency of potential targets of HIV infection within the FRT, we performed a systematic study of the expression of HIV receptors (CD4, galactosyl ceramide (GalCer)) and coreceptors (CXCR4 and CCR5) on epithelial cells and leucocytes from the ectocervix. The ectocervix is a likely first site of contact with HIV‐1 following heterosexual transmission, and expression of these receptors is likely to correlate with susceptibility to viral infection. We obtained ectocervical tissue specimens from women undergoing hysterectomy, and compared expression of these receptors among patients who were classified as being in the proliferative or secretory phases of their menstrual cycle at the time of hysterectomy, as well as from postmenopausal tissues. Epithelial cells from tissues at early and mid‐proliferative stages of the menstrual cycle express CD4, although by late proliferative and secretory phases, CD4 expression was absent or weak. In contrast, GalCer expression was uniform in all stages of the menstrual cycle. CXCR4 expression was not detected on ectocervical epithelial cells and positive staining was only evident on individual leucocytes. In contrast, CCR5 expression was detected on ectocervical epithelial cells from tissues at all stages of the menstrual cycle. Overall, our results suggest that HIV infection of cells in the ectocervix could most likely occur through GalCer and CCR5. These findings are important to define potential targets of HIV‐1 infection within the FRT, and for the future design of approaches to reduce the susceptibility of women to infection by HIV‐1.
doi_str_mv 10.1111/j.1365-2567.2004.01990.x
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The mechanism of viral transmission within the FRT and the mode of viral spread to the periphery are not well understood. To characterize the frequency of potential targets of HIV infection within the FRT, we performed a systematic study of the expression of HIV receptors (CD4, galactosyl ceramide (GalCer)) and coreceptors (CXCR4 and CCR5) on epithelial cells and leucocytes from the ectocervix. The ectocervix is a likely first site of contact with HIV‐1 following heterosexual transmission, and expression of these receptors is likely to correlate with susceptibility to viral infection. We obtained ectocervical tissue specimens from women undergoing hysterectomy, and compared expression of these receptors among patients who were classified as being in the proliferative or secretory phases of their menstrual cycle at the time of hysterectomy, as well as from postmenopausal tissues. Epithelial cells from tissues at early and mid‐proliferative stages of the menstrual cycle express CD4, although by late proliferative and secretory phases, CD4 expression was absent or weak. In contrast, GalCer expression was uniform in all stages of the menstrual cycle. CXCR4 expression was not detected on ectocervical epithelial cells and positive staining was only evident on individual leucocytes. In contrast, CCR5 expression was detected on ectocervical epithelial cells from tissues at all stages of the menstrual cycle. Overall, our results suggest that HIV infection of cells in the ectocervix could most likely occur through GalCer and CCR5. These findings are important to define potential targets of HIV‐1 infection within the FRT, and for the future design of approaches to reduce the susceptibility of women to infection by HIV‐1.</description><identifier>ISSN: 0019-2805</identifier><identifier>EISSN: 1365-2567</identifier><identifier>DOI: 10.1111/j.1365-2567.2004.01990.x</identifier><identifier>PMID: 15554931</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>CD4 Antigens - metabolism ; Cervix Uteri - immunology ; Cervix Uteri - virology ; chemokine receptor expression ; Disease Susceptibility - immunology ; Epithelial Cells - immunology ; Female ; HIV Infections - immunology ; HIV-1 - pathogenicity ; HIV‐1 ; Human immunodeficiency virus 1 ; Humans ; Immunophenotyping ; Original ; Receptors, CCR5 - metabolism ; Receptors, Chemokine - metabolism ; Receptors, CXCR4 - metabolism ; Receptors, HIV - metabolism</subject><ispartof>Immunology, 2004-12, Vol.113 (4), p.524-533</ispartof><rights>Copyright Blackwell Scientific Publications Ltd. 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Epithelial cells from tissues at early and mid‐proliferative stages of the menstrual cycle express CD4, although by late proliferative and secretory phases, CD4 expression was absent or weak. In contrast, GalCer expression was uniform in all stages of the menstrual cycle. CXCR4 expression was not detected on ectocervical epithelial cells and positive staining was only evident on individual leucocytes. In contrast, CCR5 expression was detected on ectocervical epithelial cells from tissues at all stages of the menstrual cycle. Overall, our results suggest that HIV infection of cells in the ectocervix could most likely occur through GalCer and CCR5. 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Asin, Susana ; Weldon, Sally ; Demian, Douglas J. ; Collins, Jane E. ; Gonzalez, Jorge L. ; Wira, Charles R. ; Fanger, Michael W. ; Howell, Alexandra L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5280-b69e3c12eaa517f2f2497b67f644eee6772acf1ad20548270c66efff0a3fa0023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>CD4 Antigens - metabolism</topic><topic>Cervix Uteri - immunology</topic><topic>Cervix Uteri - virology</topic><topic>chemokine receptor expression</topic><topic>Disease Susceptibility - immunology</topic><topic>Epithelial Cells - immunology</topic><topic>Female</topic><topic>HIV Infections - immunology</topic><topic>HIV-1 - pathogenicity</topic><topic>HIV‐1</topic><topic>Human immunodeficiency virus 1</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Original</topic><topic>Receptors, CCR5 - metabolism</topic><topic>Receptors, Chemokine - metabolism</topic><topic>Receptors, CXCR4 - metabolism</topic><topic>Receptors, HIV - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yeaman, Grant R.</creatorcontrib><creatorcontrib>Asin, Susana</creatorcontrib><creatorcontrib>Weldon, Sally</creatorcontrib><creatorcontrib>Demian, Douglas J.</creatorcontrib><creatorcontrib>Collins, Jane E.</creatorcontrib><creatorcontrib>Gonzalez, Jorge L.</creatorcontrib><creatorcontrib>Wira, Charles R.</creatorcontrib><creatorcontrib>Fanger, Michael W.</creatorcontrib><creatorcontrib>Howell, Alexandra L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yeaman, Grant R.</au><au>Asin, Susana</au><au>Weldon, Sally</au><au>Demian, Douglas J.</au><au>Collins, Jane E.</au><au>Gonzalez, Jorge L.</au><au>Wira, Charles R.</au><au>Fanger, Michael W.</au><au>Howell, Alexandra L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemokine receptor expression in the human ectocervix: implications for infection by the human immunodeficiency virus‐type I</atitle><jtitle>Immunology</jtitle><addtitle>Immunology</addtitle><date>2004-12</date><risdate>2004</risdate><volume>113</volume><issue>4</issue><spage>524</spage><epage>533</epage><pages>524-533</pages><issn>0019-2805</issn><eissn>1365-2567</eissn><abstract>Summary Human immunodeficiency virus‐type 1 (HIV‐1) is a sexually transmitted pathogen that can infect cells in the female reproductive tract (FRT). 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Epithelial cells from tissues at early and mid‐proliferative stages of the menstrual cycle express CD4, although by late proliferative and secretory phases, CD4 expression was absent or weak. In contrast, GalCer expression was uniform in all stages of the menstrual cycle. CXCR4 expression was not detected on ectocervical epithelial cells and positive staining was only evident on individual leucocytes. In contrast, CCR5 expression was detected on ectocervical epithelial cells from tissues at all stages of the menstrual cycle. Overall, our results suggest that HIV infection of cells in the ectocervix could most likely occur through GalCer and CCR5. These findings are important to define potential targets of HIV‐1 infection within the FRT, and for the future design of approaches to reduce the susceptibility of women to infection by HIV‐1.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15554931</pmid><doi>10.1111/j.1365-2567.2004.01990.x</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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subjects CD4 Antigens - metabolism
Cervix Uteri - immunology
Cervix Uteri - virology
chemokine receptor expression
Disease Susceptibility - immunology
Epithelial Cells - immunology
Female
HIV Infections - immunology
HIV-1 - pathogenicity
HIV‐1
Human immunodeficiency virus 1
Humans
Immunophenotyping
Original
Receptors, CCR5 - metabolism
Receptors, Chemokine - metabolism
Receptors, CXCR4 - metabolism
Receptors, HIV - metabolism
title Chemokine receptor expression in the human ectocervix: implications for infection by the human immunodeficiency virus‐type I
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