TICK-BORNE THOGOTO VIRUS-INFECTION IN MICE IS INHIBITED BY THE ORTHOMYXOVIRUS RESISTANCE GENE-PRODUCT MX1

We show that tick-transmitted Thogoto virus is sensitive to interferon -induced nuclear Mx1 protein, which is known for its specific antivira l action against orthomyxoviruses. Influenza virus-susceptible BALB/c mice (lacking a functional Mx1 gene) developed severe disease symptoms and died within days after intracerebral or intraperitoneal infection with a lethal challenge dose of Thogoto virus. In contrast, Mx1-posit ive congenic, influenza virus-resistant BALB.A2G-Mx1 mice remained hea lthy and survived. Likewise, A2G, congenic B6.A2G-Mx1 and CBA.T9-Mx1 m ice (derived from influenza virus-resistant wild mice) as well as Mx1- transgenic 979 mice proved to be resistant. Peritoneal macrophages and interferon-treated embryo cells from resistant mice exhibited the sam e resistance phenotype in vitro. Moreover, stable lines of transfected mouse 3T3 cells that constitutively express Mx1 protein showed increa sed resistance to Thogoto virus infection. We conclude that an Mx1-sen sitive step has been conserved during evolution of orthomyxoviruses an d suggest that the Mx1 gene in rodents may serve to combat infections by influenza virus-like arboviruses.