Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys

Steven E Bosinger; Qingsheng Li; Shari N Gordon; Nichole R Klatt; Lijie Duan; Luoling Xu; Nicholas Francella; Abubaker Sidahmed; Anthony J Smith; Elizabeth M Cramer; Ming Zeng; David Masopust; John V Carlis; Longsi Ran; Thomas H Vanderford; Mirko Paiardini; R. Benjamin Isett; Don A Baldwin; James G Else; Silvija I Staprans; Guido Silvestri; Ashley T Haase; David J Kelvin

doi:10.1172/JCI40115

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Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys

Journal article

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Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys

Steven E Bosinger, Qingsheng Li, Shari N Gordon, Nichole R Klatt, Lijie Duan, Luoling Xu, Nicholas Francella, Abubaker Sidahmed, Anthony J Smith, Elizabeth M Cramer, …

The Journal of clinical investigation, Vol.119(12), pp.3556-3572

2009-12-01

DOI: https://doi.org/10.1172/JCI40115

PMCID: PMC2786806

PMID: 19959874

Abstract

Natural SIV infection of sooty mangabeys (SMs) is nonprogressive despite chronic virus replication. Strikingly, it is characterized by low levels of immune activation, while pathogenic SIV infection of rhesus macaques (RMs) is associated with chronic immune activation. To elucidate the mechanisms underlying this intriguing phenotype, we used high-density oligonucleotide microarrays to longitudinally assess host gene expression in SIV-infected SMs and RMs. We found that acute SIV infection of SMs was consistently associated with a robust innate immune response, including widespread upregulation of IFN-stimulated genes (ISGs) in blood and lymph nodes. While SMs exhibited a rapid resolution of ISG expression and immune activation, both responses were observed chronically in RMs. Systems biology analysis indicated that expression of the lymphocyte inhibitory receptor LAG3, a marker of T cell exhaustion, correlated with immune activation in SIV-infected RMs but not SMs. Our findings suggest that active immune regulatory mechanisms, rather than intrinsically attenuated innate immune responses, underlie the low levels of immune activation characteristic of SMs chronically infected with SIV.

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.66 HIV; 1.66.46 HIV-1
Web Of Science research areas: Medicine, Research & Experimental
ESI research areas: Clinical Medicine

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Title: Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys
Creators: Steven E Bosinger - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Qingsheng Li - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Shari N Gordon - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Nichole R Klatt - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Lijie Duan - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Luoling Xu - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Nicholas Francella - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Abubaker Sidahmed - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Anthony J Smith - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Elizabeth M Cramer - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Ming Zeng - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
David Masopust - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
John V Carlis - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Longsi Ran - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Thomas H Vanderford - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Mirko Paiardini - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
R. Benjamin Isett - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Don A Baldwin - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
James G Else - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Silvija I Staprans - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Guido Silvestri - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Ashley T Haase - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
David J Kelvin - Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Publication Details: The Journal of clinical investigation, Vol.119(12), pp.3556-3572
Publisher: American Society for Clinical Investigation
Academic Unit: UMMG Department of Pediatrics
Language: English
Resource Type: Journal article
PMID: 19959874
PMCID: PMC2786806
Record Identifier: 991031613707302976