Missorting of LaCrosse virus nucleocapsid protein by the interferon-induced MxA GTPase involves smooth ER membranes.
The interferon-induced human MxA protein belongs to the class of dynamin-like, large guanosine-5'-triphosphatases that are involved in intracellular vesicle trafficking and organelle homeostasis. MxA shares many properties with the other members of this protein superfamily, including the propensity to self-assemble and to associate with lipid membranes. However, MxA is unique in that it has antiviral activity and inhibits the replication of several RNA viruses. Here, we determined the role of membranes for the antiviral function of MxA using LaCrosse-bunyavirus (LACV). We show that MxA does not affect trafficking and sorting of viral glycoproteins but binds and mislocates the viral nucleocapsid (N) protein into membrane-associated, large perinuclear complexes. We further demonstrate that MxA localizes to a subcompartment of the smooth endoplasmic reticulum where the viral N protein accumulates. In infected MxA-expressing cells, oligomeric MxA/N complexes are formed in close association with COP-I-positive vesicular-tubular membranes. Our results suggest that this membrane compartment is the preferred place where MxA and N interact, leading to efficient sequestration and missorting of an essential viral component.
Reichelt
Mike
M
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany.
Stertz
Silke
S
Krijnse-Locker
Jacomine
J
Haller
Otto
O
Kochs
Georg
G
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism; D018871:Endoplasmic Reticulum, Smooth / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007372:Interferons / Q000378:metabolism; D018062:La Crosse virus / Q000737:chemistry / Q000502:physiology; D016253:Microscopy, Immunoelectron; D008870:Microtubules / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism / Q000648:ultrastructure; D064547:Myxovirus Resistance Proteins; D019590:Nucleocapsid Proteins / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D013997:Time Factors; D014779:Virus Replication
C579071:MX1 protein, human; D046912:Multiprotein Complexes; D064547:Myxovirus Resistance Proteins; D019590:Nucleocapsid Proteins; D007372:Interferons; D019204:GTP-Binding Proteins