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

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 & 7 others Matthew Woods, Huldrych F. Günthard, Paul De Bakker, Daniel C. Douek, Guido Silvestri, Javier Martinez-Picado, Amalio Telenti

Research output: Contribution to journalArticle

122 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2391-2400
Number of pages10
JournalJournal of Clinical Investigation
Volume121
Issue number6
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

Fingerprint

Cercocebus atys
Macaca mulatta
HIV Infections
HIV-1
Phenotype
Infection
T-Lymphocytes
Transcriptome
Genes
CD4 Lymphocyte Count
Immunosuppression
Interferons
Disease Progression
Acquired Immunodeficiency Syndrome
HIV

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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; Woods, Matthew; Günthard, Huldrych F.; De Bakker, Paul; Douek, Daniel C.; Silvestri, Guido; Martinez-Picado, Javier; Telenti, Amalio.

In: Journal of Clinical Investigation, Vol. 121, No. 6, 01.06.2011, p. 2391-2400.

Research output: Contribution to journalArticle

Rotger, M, Dalmau, J, Rauch, A, McLaren, P, Bosinger, SE, Martinez, R, Sandler, NG, Roque, A, Liebner, J, Battegay, M, Bernasconi, E, Descombes, P, Erkizia, I, Fellay, J, Hirschel, B, Miró, JM, Palou, E, Hoffmann, M, Massanella, M, Blanco, J, Woods, M, Günthard, HF, De Bakker, P, Douek, DC, Silvestri, G, Martinez-Picado, J & Telenti, A 2011, 'Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque', Journal of Clinical Investigation, vol. 121, no. 6, pp. 2391-2400. https://doi.org/10.1172/JCI45235
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 ; Woods, Matthew ; Günthard, Huldrych F. ; De Bakker, Paul ; Douek, Daniel C. ; Silvestri, Guido ; Martinez-Picado, Javier ; Telenti, Amalio. / Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque. In: Journal of Clinical Investigation. 2011 ; Vol. 121, No. 6. pp. 2391-2400.
@article{69bc5ce96eed4db7b72a2ef6a86dae42,
title = "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.",
author = "Margalida Rotger and Judith Dalmau and Andri Rauch and Paul McLaren and Bosinger, {Steven E.} and Raquel Martinez and Sandler, {Netanya G.} and Annelys Roque and Julia Liebner and Manuel Battegay and Enos Bernasconi and Patrick Descombes and Itziar Erkizia and Jacques Fellay and Bernard Hirschel and Mir{\'o}, {Jose M.} and Eduard Palou and Matthias Hoffmann and Marta Massanella and Juli{\`a} Blanco and Matthew Woods and G{\"u}nthard, {Huldrych F.} and {De Bakker}, Paul and Douek, {Daniel C.} and Guido Silvestri and Javier Martinez-Picado and Amalio Telenti",
year = "2011",
month = "6",
day = "1",
doi = "10.1172/JCI45235",
language = "English (US)",
volume = "121",
pages = "2391--2400",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",

}

TY - JOUR

T1 - Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque

AU - Rotger, Margalida

AU - Dalmau, Judith

AU - Rauch, Andri

AU - McLaren, Paul

AU - Bosinger, Steven E.

AU - Martinez, Raquel

AU - Sandler, Netanya G.

AU - Roque, Annelys

AU - Liebner, Julia

AU - Battegay, Manuel

AU - Bernasconi, Enos

AU - Descombes, Patrick

AU - Erkizia, Itziar

AU - Fellay, Jacques

AU - Hirschel, Bernard

AU - Miró, Jose M.

AU - Palou, Eduard

AU - Hoffmann, Matthias

AU - Massanella, Marta

AU - Blanco, Julià

AU - Woods, Matthew

AU - Günthard, Huldrych F.

AU - De Bakker, Paul

AU - Douek, Daniel C.

AU - Silvestri, Guido

AU - Martinez-Picado, Javier

AU - Telenti, Amalio

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79957912712&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957912712&partnerID=8YFLogxK

U2 - 10.1172/JCI45235

DO - 10.1172/JCI45235

M3 - Article

VL - 121

SP - 2391

EP - 2400

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 6

ER -