Antivirally active MxA protein sequesters La Crosse virus nucleocapsid protein into perinuclear complexes.
Bunyaviruses replicate in the cytoplasm of infected cells. New viral particles are formed by budding of nucleocapsids into the Golgi apparatus. We have previously shown that the IFN-induced human MxA protein inhibits bunyavirus replication by an unknown mechanism. Here we demonstrate that MxA binds to the nucleocapsid protein of La Crosse virus (LACV) and colocalizes with the viral protein in cytoplasmic complexes. Electron microscopy revealed that these complexes accumulated in the perinuclear area and consisted of highly ordered fibrillary structures. A similar MxA-mediated redistribution of viral nucleocapsid proteins was detected with other bunyaviruses, such as Bunyamwera virus and Rift Valley fever virus. MxA(E645R), a carboxy-terminal mutant of MxA without antiviral activity against LACV, did not lead to complex formation. Wild-type MxA, but not MxA(E645R), was able to bind to LACV nucleocapsid protein in coimmunoprecipitation assays, demonstrating the importance of the carboxy-terminal effector domain of MxA. These results illustrate an efficient mechanism of IFN action whereby an essential virus component is trapped in cytoplasmic inclusions and becomes unavailable for the generation of new virus particles.
Kochs
Georg
G
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany. kochs@ukl.uni-freiburg.de
Janzen
Christian
C
Hohenberg
Heinz
H
Haller
Otto
O
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D019204:GTP-Binding Proteins; D006801:Humans; D018062:La Crosse virus / Q000235:genetics / Q000378:metabolism*; D064547:Myxovirus Resistance Proteins; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014709:Vero Cells
D000998:Antiviral Agents; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D019590:Nucleocapsid Proteins; D011506:Proteins; D019204:GTP-Binding Proteins