Show simple item record Rotger, M Dang, KK Fellay, J Heinzen, EL Feng, S Descombes, P Shianna, KV Ge, D Günthard, HF Goldstein, DB Telenti, A Swiss HIV Cohort Study Center for HIV/AIDS Vaccine Immunology
dc.coverage.spatial United States 2011-06-21T17:32:21Z 2010-02-26
dc.identifier.citation PLoS Pathog, 2010, 6 (2), pp. e1000781 - ?
dc.description.abstract 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.
dc.format.extent e1000781 - ?
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof PLoS Pathog
dc.relation.isversionof 10.1371/journal.ppat.1000781
dc.subject Adult
dc.subject CD4-Positive T-Lymphocytes
dc.subject Cell Separation
dc.subject Female
dc.subject Gene Expression
dc.subject Gene Expression Profiling
dc.subject Genome-Wide Association Study
dc.subject HIV Infections
dc.subject HIV-1
dc.subject Humans
dc.subject Male
dc.subject Oligonucleotide Array Sequence Analysis
dc.subject Polymorphism, Single Nucleotide
dc.subject RNA, Messenger
dc.subject Viral Load
dc.title Genome-wide mRNA expression correlates of viral control in CD4+ T-cells from HIV-1-infected individuals.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US 2010-2-0 en_US
duke.description.endpage e1000781 en_US
duke.description.issue 2 en_US
duke.description.startpage e1000781 en_US
duke.description.volume 6 en_US
dc.relation.journal Plos Pathogens en_US
pubs.issue 2
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Institutes and Provost's Academic Units
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers/Duke Institute for Brain Sciences
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Molecular Genetics and Microbiology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Center for Human Genome Variation
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Clinical Research Institute
pubs.publication-status Published online
pubs.volume 6
dc.identifier.eissn 1553-7374

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