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

被引：148

作者：

Rotger, Margalida ^{[2
,3
]}

Dalmau, Judith ^{[1
]}

Rauch, Andri ^{[4
]}

McLaren, Paul ^{[5
]}

Bosinger, Steven E. ^{[6
,7
]}

Martinez, Raquel ^{[2
,3
]}

Sandler, Netanya G. ^{[8
]}

Roque, Annelys ^{[8
]}

Liebner, Julia ^{[8
]}

Battegay, Manuel ^{[9
]}

Bernasconi, Enos ^{[10
]}

Descombes, Patrick ^{[11
]}

Erkizia, Itziar ^{[1
]}

Fellay, Jacques ^{[2
,3
]}

Hirschel, Bernard ^{[12
]}

Miro, Jose M. ^{[13
]}

Palou, Eduard ^{[14
]}

Hoffmann, Matthias ^{[15
]}

Massanella, Marta ^{[1
]}

Blanco, Julia ^{[1
]}

Woods, Matthew ^{[16
]}

Guenthard, Huldrych F. ^{[17
]}

de Bakker, Paul ^{[5
]}

Douek, Daniel C. ^{[8
]}

Silvestri, Guido ^{[6
,7
]}

Martinez-Picado, Javier ^{[1
,19
]}

Telenti, Amalio ^{[2
,3
,18
]}

机构：

[1] Hosp Badalona Germans Trias & Pujol, AIDS Res Inst IrsiCaixa, Barcelona, Spain

[2] Univ Lausanne, Lausanne, Switzerland

[3] Univ Hosp, Inst Microbiol, Lausanne, Switzerland

[4] Univ Hosp Bern, Div Infect Dis, CH-3010 Bern, Switzerland

[5] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA

[6] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA

[7] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA

[8] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[9] Univ Basel Hosp, Div Infect Dis & Hosp Epidemiol, CH-4031 Basel, Switzerland

[10] Osped Reg, Lugano, Switzerland

[11] Univ Geneva, Geneva, Switzerland

[12] Univ Hosp Geneva, Div Infect Dis, Geneva, Switzerland

[13] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain

[14] Banc de Sang & Teixits, Barcelona, Spain

[15] Kantonsspital St Gall, St Gallen, Switzerland

[16] Ragon Inst MGH MIT & Harvard, Boston, MA USA

[17] Univ Zurich, Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland

[18] SHCS, Lausanne, Switzerland

[19] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2011年 / 121卷 / 06期

基金：

加拿大健康研究院; 瑞士国家科学基金会;

关键词：

VIRUS TYPE-1 INFECTION; ANTIRETROVIRAL THERAPY; LYMPHOCYTE-ACTIVATION; IMMUNE ACTIVATION; LYMPHATIC TISSUE; EXPRESSION; DISEASE; MECHANISMS; SIGNATURES; DISCOVERY;

D O I：

10.1172/JCI45235

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：2391 / 2400

页数：10

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