Distinct Genetic Loci Control Plasma HIV-RNA and Cellular HIV-DNA Levels in HIV-1 Infection: The ANRS Genome Wide Association 01 Study

Cyril Dalmasso; Wassila Carpentier; Laurence Meyer; Christine Rouzioux; Cécile Goujard; Marie-Laure Chaix; Olivier Lambotte; Véronique Avettand-Fenoël; Sigrid Le Clerc; Laure Denis de Senneville; Christiane Deveau; Faroudy Boufassa; Patrice Debré; Jean-François Delfraissy; Philippe Broët; Ioannis Theodorou

doi:10.1371/journal.pone.0003907

Journal articles

Distinct Genetic Loci Control Plasma HIV-RNA and Cellular HIV-DNA Levels in HIV-1 Infection: The ANRS Genome Wide Association 01 Study

Cyril Dalmasso ¹ Wassila Carpentier ^{2, 3, 4} Laurence Meyer ^{5, 6} Christine Rouzioux ^{7, 8} Cécile Goujard ^{9, 6} Marie-Laure Chaix ^{7, 8} Olivier Lambotte ^{9, 6} Véronique Avettand-Fenoël ^{7, 8} Sigrid Le Clerc ¹⁰ Laure Denis de Senneville ^{3, 4} Christiane Deveau ^{5, 6} Faroudy Boufassa ^{5, 6} Patrice Debré ^{3, 4} Jean-François Delfraissy ^{9, 6} Philippe Broët ^{1, 11} Ioannis Theodorou ^{3, 4}

1 JE2492 - Méthodologie biostatistique de la génomique fonctionnelle en épidémiologie clinique

2 P3S - Plateforme Post-génomique de la Pitié-Salpêtrière

OMIQUE - UMS omique

3 Immunologie cellulaire et tissulaire

4 CHU Pitié-Salpêtrière [AP-HP]

5 Santé reproductive, sexualité, infection à VIH - épidémiologie, démographie, sciences sociales

6 AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)

7 Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant

8 CHU Necker - Enfants Malades [AP-HP]

9 Immunologie antivirale systémique et cérébrale

10 Chaire de Bioinformatique

CNAM - Conservatoire National des Arts et Métiers [CNAM]

11 Hôpital Paul Brousse

Abstract : Previous studies of the HIV-1 disease have shown that HLA and Chemokine receptor genetic variants influence disease progression and early viral load. We performed a Genome Wide Association study in a cohort of 605 HIV-1-infected seroconverters for detection of novel genetic factors that influence plasma HIV-RNA and cellular HIV-DNA levels. Most of the SNPs strongly associated with HIV-RNA levels were localised in the 6p21 major histocompatibility complex (MHC) region and were in the vicinity of class I and III genes. Moreover, protective alleles for four disease-associated SNPs in the MHC locus (rs2395029, rs13199524, rs12198173 and rs3093662) were strikingly over-represented among forty-five Long Term HIV controllers. Furthermore, we show that the HIV-DNA levels (reflecting the HIV reservoir) are associated with the same four SNPs, but also with two additional SNPs on chromosome 17 (rs6503919; intergenic region flanked by the DDX40 and YPEL2 genes) and chromosome 8 (rs2575735; within the Syndecan 2 gene). Our data provide evidence that the MHC controls both HIV replication and HIV reservoir. They also indicate that two additional genomic loci may influence the HIV reservoir.

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Journal articles

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Life Sciences [q-bio] / Human health and pathology / Infectious diseases

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Distinct Genetic Loci Control Plasma HIV-RNA and Cellular HIV-DNA Levels in HIV-1 Infection: The ANRS Genome Wide Association 01 Study

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Distinct Genetic Loci Control Plasma HIV-RNA and Cellular HIV-DNA Levels in HIV-1 Infection: The ANRS Genome Wide Association 01 Study

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