The Journal of biological chemistry 2017 10 18() pii 10.1074/jbc.M117.796839
Promyelocytic leukemia nuclear bodies (PMLNB) are sub-nuclear organelles which are the hub of numerous proteins. DNA/RNA viruses often hijack cellular-factors resident in PML-NBs to promote their proliferation in host cells. Hepatitis B virus (HBV), belonging to Hepadnaviridae family, remains undetected in early infection as it does not induce the innate immune response and is known to be the cause of several hepatic diseases leading to cirrhosis and hepatocellular carcinoma. The association of PML-NB proteins and HBV is being addressed in a number of recent studies. Here, we report that PML-NB protein Speckled 110kDa (Sp110), is SUMO1-modified and undergoes a deSUMOylation driven release from the PML-NB in presence of HBV. Intriguingly, Sp110 knock-down significantly reduced viral DNA-load in the culture supernatant by activation of type-I interferon response pathway. Further, we found that Sp110 differentially regulates several direct target genes of HBx, a viral co-factor. Subsequently, we identified Sp110, as a novel interactor of HBx and found this association to be essential for the exit of Sp110 from the PML-NB during HBV infection and HBx recruitment on the promoter of these genes. HBx, in turn, modulates the recruitment of its associated transcription cofactors p300/HDAC1 to these co-regulated genes, thereby altering the host gene expression programme in favor of viral persistence. Thus we report a mechanism by which HBV can evade host immune-response by hijacking PML-NB protein Sp110 and therefore propose it to be a novel target for antiviral therapy.