Characteristics of alpha/beta interferon induction after infection of murine fibroblasts with wild-type and mutant alphaviruses.
We examined the characteristics of interferon alpha/beta (IFN-alpha/beta) induction after alphavirus or control Sendai virus (SeV) infection of murine fibroblasts (MEFs). As expected, SeV infection of wild-type (wt) MEFs resulted in strong dimerization of IRF3 and the production of high levels of IFN-alpha/beta. In contrast, infection of MEFs with multiple alphaviruses failed to elicit detectable IFN-alpha/beta. In more detailed studies, Sindbis virus (SINV) infection caused dimerization and nuclear migration of IRF3, but minimal IFN-beta promoter activity, although surprisingly, the infected cells were competent for IFN production by other stimuli early after infection. A SINV mutant defective in host macromolecular synthesis shutoff induced IFN-alpha/beta in the MEF cultures dependent upon the activities of the TBK1 IRF3 activating kinase and host pattern recognition receptors (PRRs) PKR and MDA5 but not RIG-I. These results suggest that wild-type alphaviruses antagonize IFN induction after IRF3 activation but also may avoid detection by host PRRs early after infection.
Center for Molecular and Tumor Virology, Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
Crystal W
CW
Burke
Christina L
CL
Gardner
Joshua J
JJ
Steffan
Kate D
KD
Ryman
William B
WB
Klimstra
D000524:Alphavirus / Q000276:immunology*; D018354:Alphavirus Infections / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D005786:Gene Expression Regulation; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016898:Interferon-alpha / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis*; D051379:Mice; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D029082:Sendai virus / Q000276:immunology
D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha; C494233:Irf3 protein, mouse; D016899:Interferon-beta