Interferon-[alpha]/[beta] Genes Are Up-Regulated in Murine Brain Astrocytes After Infection With Theiler's Murine Encephalomyelitis Virus

• Published in: Journal of interferon & cytokine research Vol. 30; no. 4; p. 253
• Main Authors: Rubio, Nazario, Palomo, Marcos, Alcami, Antonio
• Format: Journal Article
• Language: English
• Published: New Rochelle Mary Ann Liebert, Inc 01.04.2010
• ISSN: 1079-9907; 1557-7465
• DOI: 10.1089/jir.2009.0050

This article reports the production of interferon alpha/beta (IFN-α/β) by SJL/J mouse brain astrocyte cultures infected with Theiler's murine encephalomyelitis virus (TMEV). cRNA from mock- and TMEV-infected SJL/J astrocytes was hybridized to the Affymetrix whole murine genome DNA microarray. Analysis revealed the up-regulation of 3 sequences coding for the IFN-α/β domain. Increased expression of mRNA coding for IFN-α was shown by conventional RT-PCR and quantitative real-time RT-PCR. According to ELISA, the concentration of IFN-α in the supernatants of infected astrocyte cultures varied with the multiplicity of infection and post-infection time. The IFN-α/β secreted was biologically active, as shown by a virus-based IFN bioassay involving Cocal virus and TMEV infection. The contribution to total interferon activity was 29% ± 3.0% for IFN-α and 52% ± 3.6% for IFN-β. IFN-α/β was induced by whole TMEV virions; induction was not achieved with either purified isolated virion capsid proteins or UV-inactivated virus. Further, induction was inhibited by specific anti-TMEV antibodies. The receptor for IFN-α/β, which is absent in uninfected astrocytes, was up-regulated after infection, as suggested by DNA hybridization analysis. The brains of infected mice contained IFN-α/β mRNA during the acute encephalitis phase, peaking at day 5 post-infection. Our findings could have significance for human diseases such as viral encephalitis and multiple sclerosis.