Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque

Rotger, Margalida; Dalmau, Judith; Rauch, Andri; McLaren, Paul; Bosinger, Steven E; Martinez, Raquel; Sandler, Netanya G; Roque, Annelys; Liebner, Julia; Battegay, Manuel; Bernasconi, Enos; Descombes, Patrick; Erkizia, Itziar; Fellay, Jacques; Hirschel, Bernard; Miró, Jose M; Palou, Eduard; Hoffmann, Matthias; Massanella, Marta; Blanco, Julià; ... (2011). Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque. Journal of clinical investigation, 121(6), pp. 2391-400. Ann Arbor, Mich.: American Society for Clinical Investigation 10.1172/JCI45235

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High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4⁺ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4⁺ and CD8⁺ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4⁺ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Rauch, Andri

ISSN:

0021-9738

Publisher:

American Society for Clinical Investigation

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:24

Last Modified:

22 Jul 2015 09:55

Publisher DOI:

10.1172/JCI45235

PubMed ID:

21555857

Web of Science ID:

000291234300037

BORIS DOI:

10.7892/boris.8269

URI:

https://boris.unibe.ch/id/eprint/8269 (FactScience: 213785)

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