{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:05:26Z","timestamp":1785423926684,"version":"3.56.0"},"reference-count":78,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD099091"],"award-info":[{"award-number":["R01HD099091"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R01HD099091"],"award-info":[{"award-number":["R01HD099091"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Innate immunity predictors of HIV-1 risk and pathogenesis vary with reproductive hormones, pregnancy, and lactation, yet the underlying mechanisms remain unclear. We hypothesized that pregnancy-associated physiological adaptations alter systemic microRNA (miRNA) expression, thereby regulating immunity, pathogenesis and susceptibility to infection. We analyzed 174 serum samples from 88 participants in a longitudinal cohort from Uganda and Zimbabwe across pre-pregnancy (PP), pregnancy (P), and postpartum breastfeeding (BF). Cell-free peripheral blood miRNAs (n = 2083) were profiled using HTG EdgeSeq. Pregnancy-specific miRNAs were identified by intersecting differentially expressed (DE) miRNAs from P vs. PP and P vs. BF comparisons. miRNA targets and pathways were analyzed using miRWalk, Cytoscape\/ClueGO, and cytoHubba. Pregnancy was associated with DE miRNAs (29 upregulated and 131 downregulated) targeting 2733 validated genes. Enriched pathways (FDR &lt; 0.05) included adaptive immune response, Hippo Signaling, Cellular Senescence, HSV-1 infection, and two cancer-related pathways. Pregnancy-enriched targets within each pathway overlapped with the HIV\u2013host interactome by 37\u201388%. Network analysis identified 47 hub genes interacting with 18 HIV-1 proteins, with Tat and gp120 being most connected viral and HLA-A being the most connected host protein. These findings indicate that pregnancy-driven systemic miRNAs target the HIV\u2013host interactome and specifically identify pregnancy-enriched central hub genes involved in cell cycle control, viral immune evasion and replication to be further investigated for their predictive value in HIV acquisition and pathogenesis in longitudinal cohorts and experimental settings.<\/jats:p>","DOI":"10.3390\/v18070753","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T13:19:31Z","timestamp":1783430371000},"page":"753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MicroRNAs Regulated by Pregnancy Target Antiviral and Cancer Immunity Overlapping with the HIV Interactome"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9293-9773","authenticated-orcid":false,"given":"Paula F. T.","family":"Cezar-de-Mello","sequence":"first","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7242-3991","authenticated-orcid":false,"given":"Jonathan M.","family":"Dreyfuss","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8910-5316","authenticated-orcid":false,"given":"Pai-Lien","family":"Chen","sequence":"additional","affiliation":[{"name":"FHI 360, Durham, NC 07701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8340-7786","authenticated-orcid":false,"given":"Hidemi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6058-8120","authenticated-orcid":false,"given":"Xiaoming","family":"Gao","sequence":"additional","affiliation":[{"name":"FHI 360, Durham, NC 07701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5748-7217","authenticated-orcid":false,"given":"Hui","family":"Pan","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Morrison","sequence":"additional","affiliation":[{"name":"FHI 360, Durham, NC 07701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9641-1325","authenticated-orcid":false,"given":"Gustavo F.","family":"Doncel","sequence":"additional","affiliation":[{"name":"CONRAD, Eastern Virginia Medical School, Norfolk, VA 23507, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3918-038X","authenticated-orcid":false,"given":"Robert L.","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-5735","authenticated-orcid":false,"given":"Raina N.","family":"Fichorova","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/infdis\/jiy113","article-title":"Increased Risk of HIV Acquisition Among Women Throughout Pregnancy and During the Postpartum Period: A Prospective Per-Coital-Act Analysis Among Women with HIV-Infected Partners","volume":"218","author":"Thomson","year":"2018","journal-title":"J. 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