5C). This observation suggests that the generation and maintenance of the compartment are microtubule-dependent. As an IFN-inducible cytoplasmic protein, the effect of MxA on DNA virus replication has just recently been recognized, and the underlying mechanisms have not been fully elucidated. In this study, we verified the anti-HBV effect of MxA in HepG2.2.15 cells. Our results suggest that MxA inhibits HBV replication by a direct interaction with the HBV core protein HBcAg via its CID domain, causing the immobilization of HBcAg and

subsequently the loss of capsid assembly. Interaction with viral nucleoprotein is the most likely common Ipilimumab research buy pathway for MxA to perform its antiviral function against RNA viruses. Nevertheless, in the case of HBV, it has been shown that MxA suppression of HBV replication involves inhibition of the export of viral mRNA from the nucleus to the cytoplasm via the PRE sequence.11 However, results from recent studies indicate that this might not be the case. Expression of two nuclear forms of the wild-type Ibrutinib only slightly decreases the expression of extra- and intracellular

HBV DNA in HepG2 cells, indicating that MxA has only a minimal effect on the replicative cycle of HBV in the nucleus.13 In HBV and HBV/MxA transgenic mice lacking functional IFN receptors, while MxA evidently inhibits HBV, the cytoplasmic HBV RNA level is not dramatically changed.12 In Vero cells, MxA inhibition of the replication of African swine fever virus (ASFV), a large double-stranded DNA virus, involves recruitment of MxA to perinuclear viral assembly sites,19 implying an interaction between ASFV and

MxA. Using biochemical and fluorescence imaging techniques, we here identified an MxA-HBcAg interaction and its necessity for the anti-HBV activity of MxA, suggesting a mechanism common to that in RNA viruses and ASFV. Our results contrast with the results of Kremsdorf and colleagues in which a lack of MxA-HBcAg interaction was indicated.11 The major cause for the differences in results and interpretation could be the experimental this website conditions. Instead of a cosedimentation assay using purified HBcAg, we performed immunoprecipitation in cells coexpressing the proteins. This may facilitate the encounter efficiency of the proteins by positioning them in a relatively physiological condition without losing possible unknown modifications required for their interaction. Identification of the interaction domain together with the colocalization of the proteins and FRET in living cells further support our conclusion. Our results showing an MxA interaction with transfected HBcAg suggest that this interaction is independent of additional HBV viral components, further supporting a direct association between MxA and HBcAg. In addition to revealing the interaction, we identified here the region in MxA responsible for the interaction.

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