TY - JOUR
T1 - Induction of innate immune responses by SIV in vivo and in vitro
T2 - Differential expression and function of RIG-I and MDA5
AU - Co, Juliene G.
AU - Witwer, Kenneth W.
AU - Gama, Lucio
AU - Zink, M. Christine
AU - Clements, Janice E.
N1 - Funding Information:
This work was supported by National Institutes of Health grants to J. E. C. [MH070306, NS047984, NS055648].
PY - 2011/10/1
Y1 - 2011/10/1
N2 - Interferon-β induction occurs during acute simian immunodeficiency virus (SIV) infection in the brain. We have examined expression and function of cytosolic RNA sensors, retinoic acid inducible gene I (RIG-I), and melanoma differentiation-associated protein 5 (MDA5), in vivo in the brain of our consistent, accelerated SIV-macaque model and in vitro in SIV-infected macaque macrophages to identify the pathway of type I interferon (IFN) induction. MDA5 messenger RNA (mRNA) and protein were expressed at higher levels in the brain than RIG-I, with protein expression correlating with the severity of disease from 42 until 84 days post-inoculation. The siRNA experiments reveal that mRNA expression of IFN-inducible gene MxA is dependent on MDA5, but not RIG-I. Finally, we demonstrate that SIV infection leads to the production of double-stranded RNA in vivo, which may act as the MDA5 ligand. We have shown for the first time to our knowledge the functional role of MDA5 in the innate immune response to SIV infection.
AB - Interferon-β induction occurs during acute simian immunodeficiency virus (SIV) infection in the brain. We have examined expression and function of cytosolic RNA sensors, retinoic acid inducible gene I (RIG-I), and melanoma differentiation-associated protein 5 (MDA5), in vivo in the brain of our consistent, accelerated SIV-macaque model and in vitro in SIV-infected macaque macrophages to identify the pathway of type I interferon (IFN) induction. MDA5 messenger RNA (mRNA) and protein were expressed at higher levels in the brain than RIG-I, with protein expression correlating with the severity of disease from 42 until 84 days post-inoculation. The siRNA experiments reveal that mRNA expression of IFN-inducible gene MxA is dependent on MDA5, but not RIG-I. Finally, we demonstrate that SIV infection leads to the production of double-stranded RNA in vivo, which may act as the MDA5 ligand. We have shown for the first time to our knowledge the functional role of MDA5 in the innate immune response to SIV infection.
UR - http://www.scopus.com/inward/record.url?scp=80052518621&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052518621&partnerID=8YFLogxK
U2 - 10.1093/infdis/jir469
DO - 10.1093/infdis/jir469
M3 - Article
C2 - 21881126
AN - SCOPUS:80052518621
SN - 0022-1899
VL - 204
SP - 1104
EP - 1114
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 7
ER -