Interferon-induced rat Mx proteins confer resistance to Rift Valley fever virus and other arthropod-borne viruses

Mx proteins belong to the interferon (IFN)-induced antiviral defense. The r at genome contains three Mx genes, ratMx1, ratMx2, and ratMx3. The Mx gene products differ in their subcellular localization and antiviral specificity . The nuclear ratMx1 protein confers resistance to influenza A virus, and t he cytoplasmic ratMx2 is active against vesicular stomatitis virus (VSV), w hereas the cytoplasmic ratMx3 protein is antivirally inactive. To investiga te the antiviral potential of the rat Mx proteins against arboviruses, a ph ylogenetically diverse group of viruses that frequently infect rodents, we studied the replication of LaCrosse virus (LACV). Rift Valley fever virus ( RVFV) (both family Bunyaviridae), and Thogoto virus (THOV) (family Orthomyx oviridae). To that end, we used transfected Vero cells constitutively expre ssing one of the rat Mx proteins. We observed that the antiviral activity o f rat Mx proteins against these arboviruses correlates with their intracell ular localization: ratMx1 is active against THOV, which replicates in the n ucleus, whereas ratMx2 inhibits bunyaviruses that replicate in the cytoplas m. The results indicate that rats have evolved two Mx proteins to efficient ly control viruses with different replication strategies.