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© Michaela Muller-Trutwin
HIV
Publication : JCI insight

TLR7 dosage polymorphism shapes interferogenesis and HIV-1 acute viremia in women.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in JCI insight - 18 Jun 2020

Azar P, Mejía JE, Cenac C, Shaiykova A, Youness A, Laffont S, Essat A, Izopet J, Passaes C, Müller-Trutwin M, Delobel P, Meyer L, Guéry JC,

Link to Pubmed [PMID] – 32554924

Link to DOI [DOI] – 10.1172/jci.insight.136047136047

JCI Insight 2020 Jun; 5(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 with lower viremia, cell-associated HIV-1 DNA, and CXCL10 (IP-10) plasma concentrations. RNA viral load was decreased by 0.85 log10 (95% CI, -1.51 to -0.18) among T/T homozygotes, who also exhibited a lower frequency of acute symptoms. TLR7 emerges as an important control locus for acute HIV-1 viremia, and the clinical phenotype for allele rs179008 T, carried by 30%-50% of European women, supports a beneficial effect of toning down TLR7-driven IFN-I production by pDCs during acute HIV-1 infection.

https://pubmed.ncbi.nlm.nih.gov/32554924