Interferon-induced human MxA protein belongs to the dynamin superfamily of
large GTPases. It exhibits antiviral activity against a variety of RNA viru
ses, including Thogoto virus, an influenza virus-like orthomyxovirus transm
itted by ticks. Here, we report that MxA blocks the transport of Thogoto vi
rus nucleocapsids into the nucleus, thereby preventing transcription of the
viral genome. This interaction can be abolished by a mAb that neutralizes
the antiviral activity of MxA. Our results reveal an antiviral mechanism wh
ereby an interferon-induced protein traps the incoming virus and interferes
with proper transport of the viral genome to its ultimate target compartme
nt within the infected cell.