{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:42:45Z","timestamp":1774316565634,"version":"3.50.1"},"reference-count":78,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R01AI140799"],"award-info":[{"award-number":["R01AI140799"]}]},{"name":"HHS | National Institutes of Health","award":["R01DK131585"],"award-info":[{"award-number":["R01DK131585"]}]},{"name":"HHS | National Institutes of Health","award":["R01AI131430"],"award-info":[{"award-number":["R01AI131430"]}]},{"name":"HHS | National Institutes of Health","award":["P30AI050410"],"award-info":[{"award-number":["P30AI050410"]}]},{"name":"HHS | National Institutes of Health","award":["5UM1AI126619"],"award-info":[{"award-number":["5UM1AI126619"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Sexually transmitted HIV infections in heterosexual men are acquired through the penis. Low adherence to condom usage and the fact that 40% of circumcised men are not protected indicate the need for additional prevention strategies. Here, we describe a new approach to evaluate the prevention of penile HIV transmission. We demonstrated that the entire male genital tract (MGT) of bone marrow\/liver\/thymus (BLT) humanized mice is repopulated with human T and myeloid cells. The majority of the human T cells in the MGT express CD4 and CCR5. Direct penile exposure to HIV leads to systemic infection including all tissues of the MGT. HIV replication throughout the MGT was reduced 100-1,000-fold by treatment with 4\u2032-ethynyl-2-fluoro-2\u2032-deoxyadenosine (EFdA), resulting in the restoration of CD4\n            <jats:sup>+<\/jats:sup>\n            T cell levels. Importantly, systemic preexposure prophylaxis with EFdA effectively protects from penile HIV acquisition.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Over 84.2 million people have been infected by the human immunodeficiency virus type 1 (HIV-1) during the past 40 years, most through sexual transmission. Men comprise approximately half of the HIV-infected population worldwide. Sexually transmitted HIV infections in exclusively heterosexual men are acquired through the penis. However, direct evaluation of HIV infection throughout the human male genital tract (MGT) is not possible. Here, we developed a new\n              <jats:italic>in vivo<\/jats:italic>\n              model that permits, for the first time, the detail analysis of HIV infection. Using BLT humanized mice, we showed that productive HIV infection occurs throughout the entire MGT and induces a dramatic reduction in human CD4 T cells compromising immune responses in this organ. Antiretroviral treatment with novel drug EFdA suppresses HIV replication in all tissues of the MGT, restores normal levels of CD4 T cells and is highly efficient at preventing penile transmission.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.02224-22","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T14:17:32Z","timestamp":1686579452000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["EFdA efficiently suppresses HIV replication in the male genital tract and prevents penile HIV acquisition"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7152-1709","authenticated-orcid":true,"given":"Martina","family":"Kovarova","sequence":"first","affiliation":[{"name":"International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Wessel","sequence":"additional","affiliation":[{"name":"International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire E.","family":"Johnson","sequence":"additional","affiliation":[{"name":"International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelby V.","family":"Anderson","sequence":"additional","affiliation":[{"name":"International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mackenzie L.","family":"Cottrell","sequence":"additional","affiliation":[{"name":"UNC Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Sykes","sequence":"additional","affiliation":[{"name":"UNC Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myron S.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3726-0482","authenticated-orcid":true,"given":"J. Victor","family":"Garcia","sequence":"additional","affiliation":[{"name":"International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001888"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu328"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/517359"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0b013e32833a8844"},{"key":"e_1_3_5_7_2","first-page":"104","article-title":"HIV and sexually transmitted diseases: lethal synergy","volume":"12","author":"Cohen MS","year":"2004","unstructured":"Cohen MS. 2004. 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