Interferon-induced, antiviral human MxA protein localizes to a distinct subcompartment of the smooth endoplasmic reticulum.
Human MxA protein belongs to the superfamily of dynamin-like large GTPases that are involved in intracellular membrane trafficking. MxA is induced by interferons-alpha/beta (IFN-alpha/beta) and is a key component of the antiviral response against RNA viruses. Here, we show that MxA localizes to membranes that are positive for specific markers of the smooth endoplasmic reticulum, such as Syntaxin17, but is excluded from other membrane compartments. Overexpression of MxA leads to a characteristic reorganization of the associated membranes. Interestingly, Hook3, mannose-6-phosphate receptor, and Lamp-1, which normally accumulate in cis- Golgi, endosomes, and lysosomes, respectively, also colocalized with MxA, indicating that these markers were redistributed to the MxA-positive compartment. Functional assays, however, did not show any effect of MxA on endocytosis or the secretory pathway. The present results demonstrate that MxA is an IFN-induced antiviral effector protein that resembles the constitutively expressed large GTPase family members in its capacity to localize to and reorganize intracellular membranes.
Stertz
Silke
S
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany.
Reichelt
Mike
M
Krijnse-Locker
Jacomine
J
Mackenzie
Jason
J
Simpson
Jeremy C
JC
Haller
Otto
O
Kochs
Georg
G
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002458:Cell Fractionation; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D018871:Endoplasmic Reticulum, Smooth / Q000378:metabolism* / Q000648:ultrastructure; D011992:Endosomes / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D016350:Leucine Zippers; D008562:Membrane Glycoproteins / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D064547:Myxovirus Resistance Proteins; D050765:Qa-SNARE Proteins / Q000378:metabolism; D012328:RNA Viruses / Q000276:immunology*; D014168:Transferrin / Q000378:metabolism; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism
D015415:Biomarkers; C028391:G protein, vesicular stomatitis virus; D016898:Interferon-alpha; C579071:MX1 protein, human; D008562:Membrane Glycoproteins; D064547:Myxovirus Resistance Proteins; D050765:Qa-SNARE Proteins; D014168:Transferrin; D014759:Viral Envelope Proteins; D016899:Interferon-beta; D019204:GTP-Binding Proteins