Characteristics of alpha/beta interferon induction after infection of murine fibroblasts with wild-type and mutant alphaviruses
- Center for Molecular and Tumor Virology, Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130 (United States)
- Feist-Weiller Cancer Center, Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130 (United States)
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.
- OSTI ID:
- 21357573
- Journal Information:
- Virology, Journal Name: Virology Journal Issue: 1 Vol. 395; ISSN VIRLAX; ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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