{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:06:07Z","timestamp":1779210367944,"version":"3.51.4"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health Fogarty Global Health Research Fellowship","award":["T32HD075731"],"award-info":[{"award-number":["T32HD075731"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Women living with HIV face an increased burden of spontaneous preterm birth (sPTB); however, the underlying immunological mechanisms of sPTB and its association with HIV infection are poorly understood. Although the limited earlier literature implicates sphingosine-1-phosphate (S1P), a lysosphingolipid signaling molecule, in reproductive biology, the association of S1P signaling with HIV and sPTB has not been investigated. We examined whether two S1P signaling components, S1P receptors and sphingosine kinases, are expressed in the female reproductive tract and whether levels are associated with HIV status or spontaneous preterm birth. We quantified the mRNA expression of sphingosine-1-phosphate receptors 1 and 3 (S1PR1\/S1PR3) and sphingosine kinases 1 and 2 (SPHK1\/SPHK2) in 167 banked vaginal swab specimens collected between 14 and 26 weeks of gestation in a longitudinal pregnancy cohort in Lusaka, Zambia. We evaluated the expression of S1PR1, S1PR3, SPHK1, and SPHK2 by real-time quantitative reverse transcription PCR (RT-qPCR) in four groups (n = 41\u201342 each): women without HIV (WWoH) with term birth (\u226537 weeks of gestation; TB), WWoH with spontaneous preterm birth (&lt;37 weeks of gestation, sPTB), women with HIV (WWH) with TB, and WWH with sPTB. We found that S1P receptors and sphingosine kinases are expressed in the female reproductive tract. SPHK1 and SPHK2 mRNA expression were generally comparable among women independent of HIV status or birth outcome, though SPHK2 trended toward higher expression in women with HIV and women with sPTB. In contrast, S1PR1 mRNA trended toward higher expression in WWH vs. WWoH overall, as well as in WWH vs. WWoH among women with sPTB. Similarly, S1PR3 mRNA expression was greater in women with HIV than in women without HIV, and WWH, both with TB and sPTB, had higher S1PR3 mRNA expression than WWoH with TB. Perturbations in S1PR1 and S1PR3 mRNA expression may be associated with inflammation related to HIV infection and spontaneous preterm birth, suggesting that further studies of S1P signaling in pregnancy, especially among women with HIV, are warranted.<\/jats:p>","DOI":"10.3390\/v18050559","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:07:26Z","timestamp":1779206846000},"page":"559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sphingosine-1-Phosphate Receptor and Kinase Expression in the Reproductive Tract Is Associated with HIV Infection and Preterm Birth in a Cohort of Pregnant Women in Zambia"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3833-2433","authenticated-orcid":false,"given":"Rachel S.","family":"Resop","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA"},{"name":"National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Innocent","family":"Mwape","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Research, Lusaka 10101, Zambia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4268-3095","authenticated-orcid":false,"given":"Yuri V.","family":"Sebasti\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5571-0793","authenticated-orcid":false,"given":"Katelyn J.","family":"Rittenhouse","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ntazana","family":"Sindano","sequence":"additional","affiliation":[{"name":"UNC Global Projects\u2014Zambia, LLC, Lusaka 10101, Zambia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Humphrey","family":"Mwape","sequence":"additional","affiliation":[{"name":"UNC Global Projects\u2014Zambia, LLC, Lusaka 10101, Zambia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret P.","family":"Kasaro","sequence":"additional","affiliation":[{"name":"UNC Global Projects\u2014Zambia, LLC, Lusaka 10101, Zambia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bellington","family":"Vwalika","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynaecology, School of Medicine, University of Zambia, Lusaka 10101, Zambia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan T.","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey S. A.","family":"Stringer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5199-3004","authenticated-orcid":false,"given":"Kristina","family":"De Paris","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","unstructured":"(2026, April 15). WHO The Global Health Observatory: HIV. 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