biostudies-literatureAzar PFrench national Agency for Research on AIDS and Viral HepatitisFondation Recherche MédicaleSidactionConseil Régional Occitanie-Midi-Pyrénées136047https://www.ebi.ac.uk/biostudies/studies/S-EPMC7406249biostudies-literatureUnknown5(12)Type I IFN (IFN-I) production by plasmacytoid DCs (pDCs) occurs during acute HIV-1 infection in response to TLR7 stimulation, but the role of pDC-derived IFN-I in controlling or promoting HIV-1 infection is ambiguous. We report here a sex-biased interferogenic phenotype for a frequent single-nucleotide polymorphism of human TLR7, rs179008, displaying an impact on key parameters of acute HIV-1 infection. We show allele rs179008 T to determine lower TLR7 protein abundance in cells from women, specifically - likely by diminishing TLR7 mRNA translation efficiency through codon usage. The hypomorphic TLR7 phenotype is mirrored by decreased TLR7-driven IFN-I production by female pDCs. Among women from the French ANRS PRIMO cohort of acute HIV-1 patients, carriage of allele rs179008 T associated JCI insightTLR7 dosage polymorphism shapes interferogenesis and HIV-1 acute viremia in women.PMC7406249DEQ20180339187ECTZ22047EP-53 studyBI25-2-02374INSPIREPassaes CCenac CMeyer LShaiykova AMuller-Trutwin MLaffont SMejia JEEssat AAzar PDelobel PYouness AGuery JCIzopet JfalseTLR7 dosage polymorphism shapes interferogenesis and HIV-1 acute viremia in women.Type I IFN (IFN-I) production by plasmacytoid DCs (pDCs) occurs during acute HIV-1 infection in response to TLR7 stimulation, but the role of pDC-derived IFN-I in controlling or promoting HIV-1 infection is ambiguous. We report here a sex-biased interferogenic phenotype for a frequent single-nucleotide polymorphism of human TLR7, rs179008, displaying an impact on key parameters of acute HIV-1 infection. We show allele rs179008 T to determine lower TLR7 protein abundance in cells from women, specifically - likely by diminishing TLR7 mRNA translation efficiency through codon usage. The hypomorphic TLR7 phenotype is mirrored by decreased TLR7-driven IFN-I production by female pDCs. Among women from the French ANRS PRIMO cohort of acute HIV-1 patients, carriage of allele rs179008 T associated 2020-01-01T00:00:00Z2020 Jun2026-05-03T20:38:59.69Z2020-11-19T13:32:36ZS-EPMC74062493255492410.1172/jci.insight.136047