Cleavage of IPS-1 in cells infected with human rhinovirus.
Rhinoviruses are prevalent human pathogens that are associated with life-threatening acute asthma exacerbations. The innate immune response to rhinovirus infection, which may play an important role in virus-induced asthma induction, has not been comprehensively investigated. We examined the innate immune response in cells infected with human rhinovirus 1a (HRV1a). Beta interferon (IFN-beta) mRNA was induced in HRV1a-infected cells at levels significantly lower than in cells infected with Sendai virus. To understand the basis for this observation, we determined whether components of the pathway leading to IFN-beta induction were altered during infection. Dimerization of the transcription factor IRF-3, which is required for synthesis of IFN-beta mRNA, is not observed in cells infected with HRV1a. Beginning at 7 h postinfection, IPS-1, a protein that is essential for cytosolic sensing of viral RNA, is degraded in HRV1a-infected cells. Induction of apoptosis by puromycin led to the cleavage of IPS-1, but treatment of HRV1a-infected cells with the pan-caspase inhibitor, zVAD, did not block cleavage of IPS-1. IPS-1 is cleaved in vitro by caspase-3 and by the picornaviral proteinases 2A(pro) and 3C(pro). Expression of HRV1a and polioviral 2A(pro) and 3C(pro) led to degradation of IPS-1 in cells. These results suggest that IPS-1 is cleaved during HRV1a infection by three different proteases. Cleavage of IPS-1 may be a mechanism for evasion of the type I IFN response, leading to a more robust infection.
Drahos
Jennifer
J
Department of Microbiology and Immunology, College of Physicians and Surgeons of Columbia University, 701 West 168th St., New York, NY 10032, USA.
Racaniello
Vincent R
VR
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis; D045744:Cell Line, Tumor; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis; D010850:Picornaviridae Infections / Q000378:metabolism*; D012229:Rhinovirus / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D048868:Adaptor Proteins, Signal Transducing; D050838:Interferon Regulatory Factor-3; C505371:MAVS protein, human; D016899:Interferon-beta