Antivirally active MxA protein sequesters La Crosse virus nucleocapsid protein into perinuclear complexes
AUTOR(ES)
Kochs, Georg
FONTE
The National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=122488Documentos Relacionados
- Expression of Human MxA Protein in Mosquito Cells Interferes with LaCrosse Virus Replication
- Human MxA Protein Protects Mice Lacking a Functional Alpha/Beta Interferon System against La Crosse Virus and Other Lethal Viral Infections
- MxA GTPase Blocks Reporter Gene Expression of Reconstituted Thogoto Virus Ribonucleoprotein Complexes
- Human MxA protein inhibits tick-borne Thogoto virus but not Dhori virus.
- Enhanced virus resistance of transgenic mice expressing the human MxA protein.