Genome-wide mRNA expression correlates of viral control in CD4+ T-cells from HIV-1-infected individuals.

Détails

Ressource 1Télécharger: BIB_43B9660D8EEB.P001.pdf (3045.06 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_43B9660D8EEB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genome-wide mRNA expression correlates of viral control in CD4+ T-cells from HIV-1-infected individuals.
Périodique
Plos Pathogens
Auteur(s)
Rotger M., Dang K.K., Fellay J., Heinzen E.L., Feng S., Descombes P., Shianna K.V., Ge D., Günthard H.F., Goldstein D.B., Telenti A., Center for HIV/AIDS Vaccine Immunology 
Collaborateur(s)
Swiss HIV Cohort Study
Contributeur(s)
Center for HIV/AIDS Vaccine Immunology , Battegay M., Bernasconi E., Böni J., Bucher HC., Bürgisser P., Calmy A., Cattacin S., Cavassini M., Dubs R., Egger M., Elzi L., Erb P., Fischer M., Flepp M., Fontana A., Francioli P., Furrer H., Fux C., Gorgievski M., Günthard H., Hirsch H., Hirschel B., Hösli I., Kahlert Ch., Kaiser L., Karrer U., Kind C., Klimkait T., Ledergerber B., Martinetti G., Martinez B., Müller N., Nadal D., Opravil M., Paccaud F., Pantaleo G., Rauch A., Regenass S., Rickenbach M., Rudin C., Schmid P., Schultze D., Schüpbach J., Speck R., Taffé P., Tarr P., Telenti A., Trkola A., Vernazza P., Weber R., Yerly S., Haynes B., Goldstein D.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Statut éditorial
Publié
Date de publication
2010
Volume
6
Numéro
2
Pages
e1000781
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
There is great interindividual variability in HIV-1 viral setpoint after seroconversion, some of which is known to be due to genetic differences among infected individuals. Here, our focus is on determining, genome-wide, the contribution of variable gene expression to viral control, and to relate it to genomic DNA polymorphism. RNA was extracted from purified CD4+ T-cells from 137 HIV-1 seroconverters, 16 elite controllers, and 3 healthy blood donors. Expression levels of more than 48,000 mRNA transcripts were assessed by the Human-6 v3 Expression BeadChips (Illumina). Genome-wide SNP data was generated from genomic DNA using the HumanHap550 Genotyping BeadChip (Illumina). We observed two distinct profiles with 260 genes differentially expressed depending on HIV-1 viral load. There was significant upregulation of expression of interferon stimulated genes with increasing viral load, including genes of the intrinsic antiretroviral defense. Upon successful antiretroviral treatment, the transcriptome profile of previously viremic individuals reverted to a pattern comparable to that of elite controllers and of uninfected individuals. Genome-wide evaluation of cis-acting SNPs identified genetic variants modulating expression of 190 genes. Those were compared to the genes whose expression was found associated with viral load: expression of one interferon stimulated gene, OAS1, was found to be regulated by a SNP (rs3177979, p = 4.9E-12); however, we could not detect an independent association of the SNP with viral setpoint. Thus, this study represents an attempt to integrate genome-wide SNP signals with genome-wide expression profiles in the search for biological correlates of HIV-1 control. It underscores the paradox of the association between increasing levels of viral load and greater expression of antiviral defense pathways. It also shows that elite controllers do not have a fully distinctive mRNA expression pattern in CD4+ T cells. Overall, changes in global RNA expression reflect responses to viral replication rather than a mechanism that might explain viral control.
Mots-clé
Adult, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/virology, Cell Separation, Female, Gene Expression, Gene Expression Profiling, Genome-Wide Association Study, HIV Infections/genetics, HIV Infections/immunology, HIV-1/immunology, Humans, Male, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, RNA, Messenger/analysis, RNA, Messenger/genetics, Viral Load
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/03/2010 16:17
Dernière modification de la notice
20/08/2019 14:47
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