Susceptibility to flavivirus-specific antiviral response of Oas1b affects the neurovirulence of the Far-Eastern subtype of tick-borne encephalitis virus

Tick-borne encephalitis virus (TBEV) is a zoonotic agent that causes fatal encephalitis in humans. 2'-5'-oligoadenylate synthetase 1b (Oas1b) has been identified as a flavivirus resistance gene, but most inbred laboratory mice do not possess a functional Oas1b gene. In this study, a congenic strain carrying a functional Oas1b gene, B6.MSM-Oas, was used to evaluate the pathogenicity of Far-Eastern TBEV. Although intracerebral infection of B6.MSM-Oas mice by Oshima 5-10 resulted in limited signs of illness, infection by Sofjin-HO resulted in death with severe neurologic signs. While Oshima 5-10 was cleared from the brain, Sofjin-HO was not cleared despite a similar level of expression of the intact Oas1b gene. Necrotic neurons with viral antigens and inflammatory reactions were observed in the brain infected with Sofjin-HO. These data indicate that the different susceptibility to the antiviral activity of Oas1b resulted in a difference in neurovirulence in the two TBEV strains.