Type I interferon inhibits Crimean-Congo hemorrhagic fever virus in human target cells

Crimean-Congo hemorrhagic fever virus (CCHFV) is a causative agent of severe hemorrhagic fever occurring sporadically in parts of Africa, Asia, Southeast Europe, and the Middle East. Its recent recognition as a potential agent of bioterrorism/biowarfare highlights the need for effective antiviral therapy. In this study, it is shown that human endothelial cells are permissive to CCHFV. It is also shown that interferon-alpha inhibits the growth of CCHFV in human endothelial and hepatoma cells, reducing virus yields by a factor of 100-1,000. By using a siRNA approach, it was demonstrated that the interferon-induced MxA GTPase is a major factor mediating the antiviral effect against CCHFV, in agreement with previous findings showing that recombinant MxA inhibits CCHFV replication by interacting with the viral nucleocapsid protein. The identification of intrinsic cellular resistance factors that block CCHFV replication may help in designing novel antiviral agents.