Transcriptional Profiling of CD4 T Cells Identifies Distinct Subgroups of HIV-1 Elite Controllers

Author:

Vigneault Francois12,Woods Matthew2,Buzon Maria J.3,Li Chun2,Pereyra Florencia2,Crosby Seth D.4,Rychert Jennifer5,Church George1,Martinez-Picado Javier36,Rosenberg Eric S.5,Telenti Amalio7,Yu Xu G.2,Lichterfeld Mathias5

Affiliation:

1. Department of Genetics, Harvard Medical School, Boston, Massachusetts

2. Ragon Institute of MGH, MIT, and Harvard, Boston, Massachusetts

3. IrsiCaixa Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

4. Department of Genetics, Washington University School of Medicine, St. Louis, Missouri

5. Infectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts

6. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain

7. Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

Abstract

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) elite controllers maintain undetectable levels of viral replication in the absence of antiretroviral therapy (ART), but their underlying immunological and virological characteristics may vary. Here, we used a whole-genome transcriptional profiling approach to characterize gene expression signatures of CD4 T cells from an unselected cohort of elite controllers. The transcriptional profiles for the majority of elite controllers were similar to those of ART-treated patients but different from those of HIV-1-negative persons. Yet, a smaller proportion of elite controllers showed an alternative gene expression pattern that was indistinguishable from that of HIV-1-negative persons but different from that of highly active antiretroviral therapy (HAART)-treated individuals. Elite controllers with the latter gene expression signature had significantly higher CD4 T cell counts and lower levels of HIV-1-specific CD8 + T cell responses but did not significantly differ from other elite controllers in terms of HLA class I alleles, HIV-1 viral loads determined by ultrasensitive single-copy PCR assays, or chemokine receptor polymorphisms. Thus, these data identify a specific subgroup of elite controllers whose immunological and gene expression characteristics approximate those of HIV-1-negative persons.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference33 articles.

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4. Bosinger, S. E., et al. 2009. Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. J. Clin. Invest. 119:3556-3572.

5. Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen

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