GTPase activity is not essential for the interferon-inducible MxA protein to inhibit the replication of hepatitis B virus.
Multiple studies have established that GTPase activity is critical for MxA to act against RNA viruses. Recently, it was shown that MxA can also restrict the replication of hepatitis B virus (HBV), a DNA virus, but the requirements for GTPase activity in inhibition of HBV by MxA remain unknown. Here, we report that GTPase-defective mutants (K83A, T103A, and L612K) can downregulate extracellular HBsAg and HBeAg and reduce the expression of extra- and intracellular HBV DNA in HepG2 cells to levels similar to that achieved by wild-type MxA. Furthermore, TMxA and T103, two nuclear forms of wild-type MxA and a GTPase-defective mutant (T103A) could only slightly decrease the expression of extra- and intracellular HBV DNA in HepG2 cells. In conclusion, GTPase activity is not essential for MxA protein to inhibit HBV replication, and MxA may have only a minimal effect on the replicative cycle of HBV in the nucleus.
Yu
Zhijian
Z
Department of Infectious Diseases, Nanfang Hospital, Nanfang Medical University, Guangzhou, China.
Wang
Zhanhui
Z
Chen
Jinjun
J
Li
Hui
H
Lin
Zhanzhou
Z
Zhang
Fan
F
Zhou
Yuanping
Y
Hou
Jinlin
J
D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology / Q000821:virology; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006509:Hepatitis B / Q000201:enzymology* / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009154:Mutation; D064547:Myxovirus Resistance Proteins; D021381:Protein Transport; D014779:Virus Replication
C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins