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Journal of Virology, November 2009, p. 11581-11587, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01490-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cleavage of IPS-1 in Cells Infected with Human Rhinovirus{triangledown}

Jennifer Drahos and Vincent R. Racaniello*

Department Microbiology and Immunology, College of Physicians and Surgeons of Columbia University, 701 West 168th Street, New York, New York 10032

Received 17 July 2009/ Accepted 31 August 2009

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-β) 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-β induction were altered during infection. Dimerization of the transcription factor IRF-3, which is required for synthesis of IFN-β 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 2Apro and 3Cpro. Expression of HRV1a and polioviral 2Apro and 3Cpro 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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Physicians and Surgeons of Columbia University, 701 West 168th St., New York, NY 10032. Phone: (212) 305-5707. Fax: (212) 305-5106. E-mail: vrr1{at}columbia.edu

{triangledown} Published ahead of print on 9 September 2009.

Journal of Virology, November 2009, p. 11581-11587, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01490-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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