TY - JOUR
T1 - Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys
AU - Bosinger, Steven E.
AU - Li, Qingsheng
AU - Gordon, Shari N.
AU - Klatt, Nichole R.
AU - Duan, Lijie
AU - Xu, Luoling
AU - Francella, Nicholas
AU - Sidahmed, Abubaker
AU - Smith, Anthony J.
AU - Cramer, Elizabeth M.
AU - Zeng, Ming
AU - Masopust, David
AU - Carlis, John V.
AU - Ran, Longsi
AU - Vanderford, Thomas H.
AU - Paiardini, Mirko
AU - Isett, R. Benjamin
AU - Baldwin, Don A.
AU - Else, James G.
AU - Staprans, Silvija I.
AU - Silvestri, Guido
AU - Haase, Ashley T.
AU - Kelvin, David J.
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - Adaptive Immunity/genetics
KW - Animals
KW - Antigens, CD/genetics
KW - CD4-Positive T-Lymphocytes/immunology
KW - Cercocebus atys/genetics
KW - Genome-Wide Association Study
KW - Immunity, Innate/genetics
KW - Interferons/genetics
KW - Lymphocyte Activation Gene 3 Protein
KW - Macaca mulatta
KW - Oligonucleotide Array Sequence Analysis
KW - Simian Acquired Immunodeficiency Syndrome/genetics
KW - Simian Immunodeficiency Virus/immunology
KW - Species Specificity
KW - Up-Regulation
UR - http://www.scopus.com/inward/record.url?scp=72849132344&partnerID=8YFLogxK
U2 - 10.1172/JCI40115
DO - 10.1172/JCI40115
M3 - Article
C2 - 19959874
AN - SCOPUS:72849132344
SN - 0021-9738
VL - 119
SP - 3556
EP - 3572
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 12
ER -