GTPase Activity of MxB Contributes to Its Nuclear Location,Interaction with Nucleoporins and Anti-HI

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The human myxovirus resistance 2(Mx2/MxB)protein,a member of interferon(IFN)-inducible dynamin-like large GTPases,restricts a number of virus infections.Inhibition of these viruses occurs at poorly-defined steps after viral entry and has a common requirement for MxB oligomerization.However,the GTPase activity is essential for the anti-viral effects of MxB against herpesviruses and HBV but not HIV-1.To understand the role of MxB GTPase activity,including GTP binding and GTP hydrolysis,in restriction of HIV-1 infection,we genetically separated these two functions and evaluated their contributions to restriction.We found that both the GTP binding and hydrolysis function of MxB involved in the restriction of HIV-1 replication.The GTPase activity of MxB contributed to its nuclear location,interaction with nucleoporins(NUPs)and HIV-1 capsids.Furthermore,MxB disrupted the association between NUPs and HIV-1 cores dependently upon its GTPase activity.The function of GTPase activity was therefore multi-faceted,led to fundamentally distinct mechanisms employed by wild-type MxB and GTPase activity defective MxB mutations to restrict HIV-1 replication.
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