INHIBITION OF BUNYAVIRUSES, PHLEBOVIRUSES, AND HANTAVIRUSES BY HUMAN MXA PROTEIN

Viruses of the Bunyaviridae family cause a variety of diseases ranging from uncomplicated fever to potentially lethal encephalitis and hemor rhagic fever. Little is known about the factors determining pathogenic ity in the vertebrate host. Interferons have been reported to be inhib itory, but their mode of action against members of the Bunyaviridae ha s not yet been elucidated. The interferon-induced MxA protein encoded on human chromosome 21 is a large GTPase with antiviral activity again st distinct negative-strand RNA viruses, notably influenza viruses. He re we show that MxA inhibits representative members of the Bunyavirida e family by interacting,vith an early step of virus replication. When constitutively expressed in stably transfected Vero cells, MxA prevent ed the accumulation of viral transcripts and proteins of Hantaan virus (genus Hantavirus). Other members of the family such as La Crosse vir us (genus Bunyavirus) and Rift Valley fever virus and sandfly fever vi rus (both genus Phlebovirus) were likewise inhibited, and virus titers were reduced up to 10(4)-fold. Our data indicate that humans have evo lved a mechanism of controlling these viruses irrespective of differen ces in viral coding strategies.