The antiviral potential of interferon-induced cotton rat Mx proteins against orthomyxovirus (influenza), rhabdovirus, and bunyavirus.

Influenza A virus (FLUAV) is an important human pathogen able to cause devastating pandemics. Recently, cotton rats have been proposed as an animal model to study the innate immune response against FLUAV and other human pathogens. The interferon (IFN)-induced Mx GTPases are part of the cell-autonomous innate immune response against viruses. We, therefore, tested the antiviral activity of the two cotton rat Mx proteins that were recently identified. The nuclear cotton rat Mx1 protein was found to be a strong inhibitor of FLUAV, whereas the cytoplasmic cotton rat Mx2 protein was inactive. Cotton rat Mx2, but not cotton rat Mx1, was able to inhibit the rhabdovirus vesicular stomatitis virus (VSV) and the bunyavirus Rift Valley fever virus (RVFV) known to replicate in the cytoplasm of infected cells. Thus, cotton rats possess two Mx proteins that have selective antiviral activity that depends on their intracellular localization. We conclude that the Mx status of cotton rats differs from that of conventional inbred mouse strains, which are known to have defective Mx genes. Therefore, cotton rats are a suitable animal model to study experimental infections with FLUAV and other RNA viruses.