{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T08:50:46Z","timestamp":1779353446154,"version":"3.51.4"},"reference-count":63,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"vor","delay-in-days":31,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Research Council, Advanced","award":["670424"],"award-info":[{"award-number":["670424"]}]},{"name":"Aidsfonds","award":["P-11118"],"award-info":[{"award-number":["P-11118"]}]},{"name":"Scientific Research NWO","award":["863.13.025"],"award-info":[{"award-number":["863.13.025"]}]},{"name":"Scientific Research NWO","award":["91718331"],"award-info":[{"award-number":["91718331"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern AIDS Soc"],"published-print":{"date-parts":[[2019,3]]},"abstract":"Abstract<\/jats:title>Introduction<\/jats:title>The significant rise in incidence of Hepatitis C virus (HCV<\/jats:styled-content>) infection among men\u2010who\u2010have\u2010sex\u2010with\u2010men (MSM<\/jats:styled-content>) living with HIV<\/jats:styled-content>\u20101 suggests that HCV<\/jats:styled-content> under specific circumstances is transmitted via sexual contact. During sexual transmission HCV<\/jats:styled-content> has to cross the epithelial barrier to either directly enter the blood stream or indirectly via mucosal immune cells. However, the mechanisms of sexual transmission of HCV<\/jats:styled-content> remain unclear. We investigated the role of Langerhans cells (LC<\/jats:styled-content>s) in HCV<\/jats:styled-content> susceptibility during sexual contact as LC<\/jats:styled-content>s are among the first cells in mucosal tissues to encounter invading viruses.<\/jats:p><\/jats:sec>Methods<\/jats:title>We investigated the phenotype of primary LC<\/jats:styled-content>s in anal biopsies from MSM<\/jats:styled-content> living with HIV<\/jats:styled-content>\u20101. To investigate the role of primary LC<\/jats:styled-content>s in HCV<\/jats:styled-content> infection and transmission, we have used both isolated primary skin LC<\/jats:styled-content>s and the ex\u00a0vivo<\/jats:italic> tissue transmission model.<\/jats:p><\/jats:sec>Results<\/jats:title>Our data identified an important role for mucosal LC<\/jats:styled-content>s in facilitating HCV<\/jats:styled-content> transmission after HIV<\/jats:styled-content>\u20101 exposure or immune activation. LC<\/jats:styled-content>s were detected within mucosal anal tissues obtained from HIV<\/jats:styled-content>\u20101 positive MSM<\/jats:styled-content> biopsies. In order to perform functional studies, we used primary LC<\/jats:styled-content>s from skin, which have a similar phenotype as mucosal LC<\/jats:styled-content>s. Immature LC<\/jats:styled-content>s were neither infected nor transmitted HCV<\/jats:styled-content> to hepatocytes. Notably, exposure to HIV<\/jats:styled-content>\u20101 significantly increased HCV<\/jats:styled-content> transmission by LC<\/jats:styled-content>s in the ex\u00a0vivo<\/jats:italic> transmission model. HIV<\/jats:styled-content>\u20101 replication was crucial for the increased HCV<\/jats:styled-content> transmission as HIV<\/jats:styled-content>\u20101 inhibitors significantly reduced HIV<\/jats:styled-content>\u20101\u2010induced HCV<\/jats:styled-content> transmission. Moreover, tissue immune activation of LC<\/jats:styled-content>s also increased HCV<\/jats:styled-content> transmission to target cells.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Thus, our data strongly indicate that HIV<\/jats:styled-content>\u20101 or immune activation in MSM<\/jats:styled-content> leads to capture of HCV<\/jats:styled-content> by mucosal LC<\/jats:styled-content>s, which might facilitate transmission to other cells or allow entry of HCV<\/jats:styled-content> into the blood. This novel transmission mechanism by LC<\/jats:styled-content>s also implicates that the activation state of LC<\/jats:styled-content>s is an important cellular determinant for HCV<\/jats:styled-content> susceptibility after sexual contact.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25268","type":"journal-article","created":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T06:35:31Z","timestamp":1554100531000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["HIV<\/scp>\u20101 exposure and immune activation enhance sexual transmission of Hepatitis C virus by primary Langerhans cells"],"prefix":"10.1002","volume":"22","author":[{"given":"Bernadien M","family":"Nijmeijer","sequence":"first","affiliation":[{"name":"Department of Experimental Immunology Amsterdam Infection and Immunity Institute Amsterdam University Medical Centers University of Amsterdam Amsterdam The 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Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie M","family":"Koekkoek","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology Clinical Virology Laboratory Amsterdam University Medical Centers University of Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Molenkamp","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology Clinical Virology Laboratory Amsterdam University Medical Centers University of Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janke","family":"Schinkel","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology Clinical Virology Laboratory Amsterdam University Medical Centers University of Amsterdam Amsterdam The 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