Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque
Margalida Rotger, … , Javier Martinez-Picado, Amalio Telenti
Margalida Rotger, … , Javier Martinez-Picado, Amalio Telenti
Published May 9, 2011
Citation Information: J Clin Invest. 2011;121(6):2391-2400. https://doi.org/10.1172/JCI45235.
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Research Article AIDS/HIV

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

Abstract

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.

Authors

Margalida Rotger, Judith Dalmau, Andri Rauch, Paul McLaren, Steven E. Bosinger, Raquel Martinez, Netanya G. Sandler, Annelys Roque, Julia Liebner, Manuel Battegay, Enos Bernasconi, Patrick Descombes, Itziar Erkizia, Jacques Fellay, Bernard Hirschel, Jose M. Miró, Eduard Palou, Matthias Hoffmann, Marta Massanella, Julià Blanco, Matthew Woods, Huldrych F. Günthard, Paul de Bakker, Daniel C. Douek, Guido Silvestri, Javier Martinez-Picado, Amalio Telenti

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Figure 4

Analysis of the candidate VNP signature in an independent CD4+ T cell expression data set.

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Analysis of the candidate VNP signature in an independent CD4+ T cell ex...
The signature associated with the VNP profile upon transcriptome analysis in humans and nonhumans was tested in an independent validation set of 153 individuals, contributing CD4+ T cell expression data across all levels of viral set point after seroconversion. Correlations with individual gene expression levels and viral set point after seroconversion are shown in the 6 top panels. Correlations with disease progression, as indicated by time to CD4+ T cell count depletion to fewer than 350 cells/μl, are shown in the 6 bottom panels. Multiple probes for 1 gene are shown in different colors: orange/red is used for genes differentially upregulated in RPs, and blue/light blue is used for genes differentially upregulated in the VNPs. Where there are 2 P values, the first value represents the red/blue lines, and the second value represents the orange/light blue lines. Each dot represents an individual. The regression lines from the linear models are shown.