{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:25:40Z","timestamp":1790011540993,"version":"4.0.1"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T00:00:00Z","timestamp":1515974400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD072663"],"award-info":[{"award-number":["R01HD072663"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006521","name":"Stanford University School of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006521","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern AIDS Soc"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>HIV affects more women than any other life\u2010threatening infectious agent, and most infections are sexually transmitted. HIV must breach the female genital tract mucosal barrier to establish systemic infection, and clinical studies indicate virus more easily evades this barrier in women using depot\u2010medroxyprogesterone acetate (DMPA) and other injectable progestins for contraception. Identifying a potential mechanism for this association, we learned DMPA promotes susceptibility of wild\u2010type mice to genital herpes simplex virus type 2 (HSV\u20102) infection by reducing genital tissue expression of the cell\u2010cell adhesion molecule desmoglein\u20101 (DSG\u20101) and increasing genital mucosal permeability. Conversely, DMPA\u2010mediated increases in genital mucosal permeability and HSV\u20102 susceptibility were eliminated in mice concomitantly administered exogenous oestrogen (E). To confirm and extend these findings, herein we used humanized mice to define effects of systemic DMPA and intravaginal (ivag) E administration on susceptibility to genital infection with cell\u2010associated HIV\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Effects of DMPA or an intravaginal (ivag) E cream on engraftment of NOD\u2010scid\u2010IL\u20102Rgc<jats:sup>null<\/jats:sup>\u00a0(NSG) mice with human peripheral blood mononuclear cells (hPBMCs) were defined with flow cytometry. Confocal microscopy was used to evaluate effects of DMPA, DMPA and E cream, or DMPA and the pharmacologically active component of the cream on vaginal tissue DSG\u20101 expression and genital mucosal permeability to low molecular weight (LMW) molecules and hPBMCs. In other studies, hPBMC\u2010engrafted NSG mice (hPBMC\u2010NSG) received DMPA or DMPA and ivag E cream before genital inoculation with 10<jats:sup>6<\/jats:sup> HIV\u20101\u2010infected hPBMCs. Mice were euthanized 10\u00a0days after infection, and plasma HIV\u20101 load quantified by qRT\u2010PCR and splenocytes used to detect HIV\u20101 p24 antigen via immunohistochemistry and infectious virus via TZM\u2010bl luciferase assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Whereas hPBMC engraftment was unaffected by DMPA or E treatment, mice administered DMPA and E (cream or the pharmacologically active cream component) displayed greater vaginal tissue expression of DSG\u20101 protein and decreased vaginal mucosal permeability to LMW molecules and hPBMCs versus DMPA\u2010treated mice. DMPA\u2010treated hPBMC\u2010NSG mice were also uniformly susceptible to genital transmission of cell\u2010associated HIV\u20101, while no animal concomitantly administered DMPA and E cream acquired systemic HIV\u20101 infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Exogenous E administration reduces susceptibility of DMPA\u2010treated humanized mice to genital HIV\u20101 infection.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25063","type":"journal-article","created":{"date-parts":[[2018,1,16]],"date-time":"2018-01-16T12:10:18Z","timestamp":1516104618000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Exogenous oestrogen inhibits genital transmission of cell\u2010associated HIV\u20101 in DMPA\u2010treated humanized mice"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8829-4549","authenticated-orcid":false,"given":"Nirk E","family":"Quispe Calla","sequence":"first","affiliation":[{"name":"Department of Comparative Medicine Stanford University School of Medicine Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2494-8184","authenticated-orcid":false,"given":"Rodolfo D","family":"Vicetti Miguel","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine Stanford University School of Medicine Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa E","family":"Glick","sequence":"additional","affiliation":[{"name":"The Ohio State University (OSU) College of Veterinary Medicine Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4277-8315","authenticated-orcid":false,"given":"Jesse J","family":"Kwiek","sequence":"additional","affiliation":[{"name":"Department of Microbiology OSU College of Arts and Sciences Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle M","family":"Gabriel","sequence":"additional","affiliation":[{"name":"OSU School of Health and Rehabilitation Sciences Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L","family":"Cherpes","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine Stanford University School of Medicine Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,15]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"HIV\/AIDS JUNPo. 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