title: Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys.
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.
authors: Department of Pathology and Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Steven E
authors: SE
authors: Bosinger
authors: Qingsheng
authors: Q
authors: Li
authors: Shari N
authors: SN
authors: Gordon
authors: Nichole R
authors: NR
authors: Klatt
authors: Lijie
authors: L
authors: Duan
authors: Luoling
authors: L
authors: Xu
authors: Nicholas
authors: N
authors: Francella
authors: Abubaker
authors: A
authors: Sidahmed
authors: Anthony J
authors: AJ
authors: Smith
authors: Elizabeth M
authors: EM
authors: Cramer
authors: Ming
authors: M
authors: Zeng
authors: David
authors: D
authors: Masopust
authors: John V
authors: JV
authors: Carlis
authors: Longsi
authors: L
authors: Ran
authors: Thomas H
authors: TH
authors: Vanderford
authors: Mirko
authors: M
authors: Paiardini
authors: R Benjamin
authors: RB
authors: Isett
authors: Don A
authors: DA
authors: Baldwin
authors: James G
authors: JG
authors: Else
authors: Silvija I
authors: SI
authors: Staprans
authors: Guido
authors: G
authors: Silvestri
authors: Ashley T
authors: AT
authors: Haase
authors: David J
authors: DJ
authors: Kelvin
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016665:Cercocebus atys / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D055106:Genome-Wide Association Study; D007113:Immunity, Innate / Q000235:genetics*; D007372:Interferons / Q000235:genetics; D008253:Macaca mulatta; D020411:Oligonucleotide Array Sequence Analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity*; D013045:Species Specificity; D015854:Up-Regulation; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D007372:Interferons; D000093322:Lymphocyte Activation Gene 3 Protein