Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I
State Key Laboratory of Molecular Virology and Genetic Engineering, Institute of Pathogen Biology, Peking Union Medical College & Chinese Academy of Medical Sciences, # 9 Dong Dan San Tiao, Dongcheng District, Beijing 100730, P. R. China
Virology Journal 2011, 8:526 doi:10.1186/1743-422X-8-526Published: 8 December 2011
The nonstructural protein 1 (NSP1) of rotavirus has been reported to block interferon (IFN) signaling by mediating proteasome-dependent degradation of IFN-regulatory factors (IRFs) and (or) the β-transducin repeat containing protein (β-TrCP). However, in addition to these targets, NSP1 may subvert innate immune responses via other mechanisms.
The NSP1 of rotavirus OSU strain as well as the IRF3 binding domain truncated NSP1 of rotavirus SA11 strain are unable to degrade IRFs, but can still inhibit host IFN response, indicating that NSP1 may target alternative host factor(s) other than IRFs. Overexpression of NSP1 can block IFN-β promoter activation induced by the retinoic acid inducible gene I (RIG-I), but does not inhibit IFN-β activation induced by the mitochondrial antiviral-signaling protein (MAVS), indicating that NSP1 may target RIG-I. Immunoprecipitation experiments show that NSP1 interacts with RIG-I independent of IRF3 binding domain. In addition, NSP1 induces down-regulation of RIG-I in a proteasome-independent way.
Our findings demonstrate that inhibition of RIG-I mediated type I IFN responses by NSP1 may contribute to the immune evasion of rotavirus.