{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T18:07:54Z","timestamp":1748628474481,"version":"3.37.3"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["HD 42402, HD 47177, HD 57784, HD 073977 and HD 073952"],"award-info":[{"award-number":["HD 42402, HD 47177, HD 57784, HD 073977 and HD 073952"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","award":["84177"],"award-info":[{"award-number":["84177"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Some mother-to-child transmission (MTCT) studies suggest that allelic variations of Fc gamma receptors (Fc\u03b3R) play a role in infant HIV-1 acquisition, but findings are inconsistent. To address the limitations of previous studies, the present study investigates the association between perinatal HIV-1 transmission and Fc\u03b3R variability in three cohorts of South African infants born to women living with HIV-1.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This nested case-control study combines <jats:italic>FCGR<\/jats:italic> genotypic data from three perinatal cohorts at two hospitals in Johannesburg, South Africa. Children with perinatally-acquired HIV-1 (cases, n = 395) were compared to HIV-1-exposed uninfected children (controls, n = 312). All study participants were black South Africans and received nevirapine for prevention of MTCT. Functional variants were genotyped using a multiplex ligation-dependent probe amplification assay, and their representation compared between groups using logistic regression analyses.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p><jats:italic>FCGR3A<\/jats:italic> gene duplication associated with HIV-1 acquisition (OR = 10.27; 95% CI 2.00\u201352.65; <jats:italic>P<\/jats:italic> = 0.005) as did the Fc\u03b3RIIb-232TT genotype even after adjusting for <jats:italic>FCGR3A<\/jats:italic> copy number and <jats:italic>FCGR3B<\/jats:italic> genotype (AOR = 1.72; 95%CI 1.07\u20132.76; <jats:italic>P<\/jats:italic> = 0.024). The association between Fc\u03b3RIIb-232TT genotype and HIV-1 acquisition was further strengthened (AOR = 2.28; 95%CI 1.11\u20134.69; <jats:italic>P<\/jats:italic> = 0.024) if adjusted separately for <jats:italic>FCGR2C<\/jats:italic> c.134-96C&gt;T. Homozygous Fc\u03b3RIIIb-HNA1a did not significantly associate with HIV-1 acquisition in a univariate model (OR = 1.42; 95%CI 0.94\u20132.16; <jats:italic>P<\/jats:italic> = 0.098) but attained significance after adjustment for <jats:italic>FCGR3A<\/jats:italic> copy number and <jats:italic>FCGR2B<\/jats:italic> genotype (AOR = 1.55; 95%CI 1.01\u20132.38; <jats:italic>P<\/jats:italic> = 0.044). Both Fc\u03b3RIIb-232TT (AOR = 1.83; 95%CI 1.13\u20132.97; <jats:italic>P<\/jats:italic> = 0.014) and homozygous Fc\u03b3RIIIb-HNA1a (AOR = 1.66; 95%CI 1.07\u20132.57; <jats:italic>P<\/jats:italic> = 0.025) retained significance when birthweight and breastfeeding were added to the model. The common <jats:italic>FCGR2A<\/jats:italic> and <jats:italic>FCGR3A<\/jats:italic> polymorphisms did not associate with HIV-1 acquisition.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Collectively, our findings suggest that the Fc\u03b3RIIb-232TT genotype exerts a controlling influence on infant susceptibility to HIV-1 infection. We also show a role for less studied variants\u2013<jats:italic>FCGR3A<\/jats:italic> duplication and homozygous HNA1a. These findings provide additional insight into a role for Fc\u03b3Rs in HIV-1 infection in children.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0273933","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T20:43:58Z","timestamp":1662756238000},"page":"e0273933","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["FCGR3A gene duplication, Fc\u03b3RIIb-232TT and Fc\u03b3RIIIb-HNA1a associate with an increased risk of vertical acquisition of HIV-1"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1329-7785","authenticated-orcid":true,"given":"Joy","family":"Ebonwu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ria","family":"Lassauni\u00e8re","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Paximadis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renate","family":"Strehlau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenda E.","family":"Gray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-8665","authenticated-orcid":true,"given":"Louise","family":"Kuhn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0991-1690","authenticated-orcid":true,"given":"Caroline T.","family":"Tiemessen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"issue":"2","key":"pone.0273933.ref001","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.immuni.2017.07.009","article-title":"Fc\u03b3 Receptor Function and the Design of Vaccination Strategies","volume":"47","author":"S 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