title: Transcriptome analysis of primary monocytes shows global down-regulation of genetic networks in HIV viremic patients versus long-term non-progressors.
abstract: Despite significant contributions of monocytes to HIV persistence, the genomic basis of HIV-infection of monocytes and its association with plasma viremia remain elusive. To understand HIV interactions with monocytes during disease progression, monocytic transcriptomes from long-term non-progressors (LTNP), HIV+ patients with viral load <1000, with viral load >1000, and seronegative controls were analyzed using Illumina microarray. Differentially expressed genes were identified (fold change >2; adjusted p<0.05) and GSEA between HIV+ groups demonstrated that the down-regulation of the pathways including Toll-like receptor (TLR) signaling, cytokine-cytokine receptor interaction, cell cycle and apoptosis was significantly associated with the viremic groups, whereas their up-regulation with the LTNP group. The down-regulation of TLR pathway in the viremic patients was exemplified by the decreased expression of TLR with the subsequent tuning down of MAPK, NF-κB, JAK-STAT, and IRF cascades. These data provide the first transcriptomic distinction between HIV+ progressors and LTNPs based on primary monocytes.
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia. jingqin.wu@newcastle.edu.au
authors.forename: Jing Qin
authors.initials: JQ
authors.lastname: Wu
authors.forename: Tara Ruth
authors.initials: TR
authors.lastname: Sassé
authors.forename: Georg
authors.initials: G
authors.lastname: Wolkenstein
authors.forename: Viviane
authors.initials: V
authors.lastname: Conceicao
authors.forename: Monica Miranda
authors.initials: MM
authors.lastname: Saksena
authors.forename: Maly
authors.initials: M
authors.lastname: Soedjono
authors.forename: Suneth S
authors.initials: SS
authors.lastname: Perera
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Dominic E
authors.initials: DE
authors.lastname: Dwyer
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Saksena
mesh_terms: D000328:Adult; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D059467:Transcriptome; D014766:Viremia / Q000276:immunology* / Q000821:virology
chemical_list: D051193:Toll-Like Receptors