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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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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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.</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. Dec 2004</rights><rights>2004 Blackwell Publishing Ltd 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5280-b69e3c12eaa517f2f2497b67f644eee6772acf1ad20548270c66efff0a3fa0023</citedby><cites>FETCH-LOGICAL-c5280-b69e3c12eaa517f2f2497b67f644eee6772acf1ad20548270c66efff0a3fa0023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782606/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782606/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15554931$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Chemokine receptor expression in the human ectocervix: implications for infection by the human immunodeficiency virus‐type I</title><title>Immunology</title><addtitle>Immunology</addtitle><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.</description><subject>CD4 Antigens - metabolism</subject><subject>Cervix Uteri - immunology</subject><subject>Cervix Uteri - virology</subject><subject>chemokine receptor expression</subject><subject>Disease Susceptibility - immunology</subject><subject>Epithelial Cells - immunology</subject><subject>Female</subject><subject>HIV Infections - immunology</subject><subject>HIV-1 - pathogenicity</subject><subject>HIV‐1</subject><subject>Human immunodeficiency virus 1</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Original</subject><subject>Receptors, CCR5 - metabolism</subject><subject>Receptors, Chemokine - metabolism</subject><subject>Receptors, CXCR4 - metabolism</subject><subject>Receptors, HIV - metabolism</subject><issn>0019-2805</issn><issn>1365-2567</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks2O0zAUhSMEYjoDr4AsFuwSbMd2EiSQRhUDlWbEBtaW615Tl8QOdlKaDeIReEaeBIdWw8AGvPHP_c6R7XOzDBFckDSe7wpSCp5TLqqCYswKTJoGF4d72eK2cD9b4HSc0xrzs-w8xl3alpjzh9kZ4ZyzpiSL7OtyC53_ZB2gABr6wQcEhz5AjNY7ZB0atoC2Y6ccAj14DWFvDy-Q7frWajUkKCKTRNaZVJ816-mOxnbd6PwGjNUWnJ7Q3oYx_vj2fZh6QKtH2QOj2giPT_NF9uHq9fvl2_z63ZvV8vI61zzdP1-LBkpNKCjFSWWooayp1qIygjEAEFVFlTZEbSjmrKYV1kKAMQar0iiMaXmRvTr69uO6g40GNwTVyj7YToVJemXlnxVnt_Kj30tS1VRgkQyenQyC_zxCHGRno4a2VQ78GKWocFPVDfsnmAxFKeoygU__And-DC79gkxhMlYTNrvVR0gHH2MAc3tlguXcCnIn58TlnLicW0H-agV5SNInd5_8W3jKPgEvj8AX28L038ZydXMzr8qf-SrG9w</recordid><startdate>200412</startdate><enddate>200412</enddate><creator>Yeaman, Grant R.</creator><creator>Asin, Susana</creator><creator>Weldon, Sally</creator><creator>Demian, Douglas J.</creator><creator>Collins, Jane E.</creator><creator>Gonzalez, Jorge L.</creator><creator>Wira, Charles R.</creator><creator>Fanger, Michael W.</creator><creator>Howell, Alexandra L.</creator><general>Blackwell Science Ltd</general><general>Wiley Subscription Services, Inc</general><general>Blackwell Science Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QR</scope><scope>7T5</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200412</creationdate><title>Chemokine receptor expression in the human ectocervix: implications for infection by the human immunodeficiency virus‐type I</title><author>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.</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). 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.</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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