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Abstract
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.