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• W2995538685 abstract "•IFN-α inducible MX2 potently inhibited HBV replication driven by episomal templates. •MX2 reduced HBV RNA by significantly decreasing HBV RNA transcription and slightly accelerating its decay. •MX2 contributes substantially to the anti-HBV activity of IFN-α. •MX2 but not the homologous MX1 efficiently inhibited HBV infection of HepG2-NTCP cells and primary human hepatocytes. •Multiple MX2 determinants including GTPase activity and oligomerization status were required for anti-HBV activity. Background & Aims Non-cytolytic cure of HBV-infected hepatocytes by cytokines, including type I interferons (IFNs), is of importance for resolving acute and chronic infection. However, as IFNs stimulate hundreds of genes, those most relevant for HBV suppression remain largely unknown. Amongst them are the large myxovirus resistance (Mx) GTPases. Human MX1 (or MxA) is active against many RNA viruses, while MX2 (or MxB) was recently found to restrict HIV-1, HCV, and herpesviruses. Herein, we investigated the anti-HBV activity of MX2. Methods The potential anti-HBV activity of MX2 and functional variants were assessed in transfected and HBV-infected hepatoma cells and primary human hepatocytes, employing multiple assays to analyze the synthesis and decay of HBV nucleic acids. The specific roles of MX2 in IFN-α-driven inhibition of HBV transcription and replication were assessed by MX2-specific shRNA interference (RNAi). Results Both MX2 alone and IFN-α substantially inhibited HBV replication, due to significant deceleration of the synthesis and slight acceleration of the turnover of viral RNA. RNAi knockdown of MX2 significantly reduced the inhibitory effects of IFN-α. Strikingly, MX2 inhibited HBV infection by reducing covalently closed circular DNA (cccDNA), most likely by indirectly impairing the conversion of relaxed circular DNA to cccDNA rather than by destabilizing existing cccDNA. Various mutations affecting the GTPase activity and oligomerization status reduced MX2's anti-HBV activity. Conclusion MX2 is an important IFN-α inducible effector that decreases HBV RNA levels but can also potently inhibit HBV infection by indirectly impairing cccDNA formation. MX2 likely has the potential for therapeutic applications aimed at curing HBV infection by eliminating cccDNA. Lay summary This study shows that the protein MX2, which is induced by interferon-α, has important anti-hepatitis B virus (HBV) effector functions. MX2 can reduce the amount of covalently closed circular DNA, which is the form of DNA that HBV uses to maintain viral persistence within hepatocytes. MX2 also reduces HBV RNA levels by downregulating synthesis of viral RNA. MX2 likely represents a novel intrinsic HBV inhibitor that could have therapeutic potential, as well as being useful for improving our understanding of the complex biology of HBV and the antiviral mechanisms of interferon-α. Non-cytolytic cure of HBV-infected hepatocytes by cytokines, including type I interferons (IFNs), is of importance for resolving acute and chronic infection. However, as IFNs stimulate hundreds of genes, those most relevant for HBV suppression remain largely unknown. Amongst them are the large myxovirus resistance (Mx) GTPases. Human MX1 (or MxA) is active against many RNA viruses, while MX2 (or MxB) was recently found to restrict HIV-1, HCV, and herpesviruses. Herein, we investigated the anti-HBV activity of MX2. The potential anti-HBV activity of MX2 and functional variants were assessed in transfected and HBV-infected hepatoma cells and primary human hepatocytes, employing multiple assays to analyze the synthesis and decay of HBV nucleic acids. The specific roles of MX2 in IFN-α-driven inhibition of HBV transcription and replication were assessed by MX2-specific shRNA interference (RNAi). Both MX2 alone and IFN-α substantially inhibited HBV replication, due to significant deceleration of the synthesis and slight acceleration of the turnover of viral RNA. RNAi knockdown of MX2 significantly reduced the inhibitory effects of IFN-α. Strikingly, MX2 inhibited HBV infection by reducing covalently closed circular DNA (cccDNA), most likely by indirectly impairing the conversion of relaxed circular DNA to cccDNA rather than by destabilizing existing cccDNA. Various mutations affecting the GTPase activity and oligomerization status reduced MX2's anti-HBV activity. MX2 is an important IFN-α inducible effector that decreases HBV RNA levels but can also potently inhibit HBV infection by indirectly impairing cccDNA formation. MX2 likely has the potential for therapeutic applications aimed at curing HBV infection by eliminating cccDNA." @default.
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• W2995538685 date "2020-05-01" @default.
• W2995538685 modified "2023-10-06" @default.
• W2995538685 title "Interferon-inducible MX2 is a host restriction factor of hepatitis B virus replication" @default.
• W2995538685 cites W1525096919 @default.
• W2995538685 cites W1552626038 @default.
• W2995538685 cites W1563075736 @default.
• W2995538685 cites W1585420923 @default.
• W2995538685 cites W1799137450 @default.
• W2995538685 cites W1844576826 @default.
• W2995538685 cites W1882530951 @default.
• W2995538685 cites W1896078937 @default.
• W2995538685 cites W1969776963 @default.
• W2995538685 cites W1971070935 @default.
• W2995538685 cites W1974586894 @default.
• W2995538685 cites W1984314246 @default.
• W2995538685 cites W1986829091 @default.
• W2995538685 cites W1990662760 @default.
• W2995538685 cites W1998938204 @default.
• W2995538685 cites W2008517556 @default.
• W2995538685 cites W2009154021 @default.
• W2995538685 cites W2010338556 @default.
• W2995538685 cites W2015763479 @default.
• W2995538685 cites W2019406621 @default.
• W2995538685 cites W2020265617 @default.
• W2995538685 cites W2027680432 @default.
• W2995538685 cites W2031174462 @default.
• W2995538685 cites W2033162292 @default.
• W2995538685 cites W2037525015 @default.
• W2995538685 cites W2039325208 @default.
• W2995538685 cites W2042304504 @default.
• W2995538685 cites W2043726848 @default.
• W2995538685 cites W2046082575 @default.
• W2995538685 cites W2050098166 @default.
• W2995538685 cites W2050385094 @default.
• W2995538685 cites W2051173965 @default.
• W2995538685 cites W2061857131 @default.
• W2995538685 cites W2063295060 @default.
• W2995538685 cites W2064823659 @default.
• W2995538685 cites W2069475314 @default.
• W2995538685 cites W2079671323 @default.
• W2995538685 cites W2081563673 @default.
• W2995538685 cites W2088160623 @default.
• W2995538685 cites W2089108066 @default.
• W2995538685 cites W2090009581 @default.
• W2995538685 cites W2096907436 @default.
• W2995538685 cites W2101032357 @default.
• W2995538685 cites W2114174430 @default.
• W2995538685 cites W2115819181 @default.
• W2995538685 cites W2120426460 @default.
• W2995538685 cites W2122224350 @default.
• W2995538685 cites W2124727151 @default.
• W2995538685 cites W2129480749 @default.
• W2995538685 cites W2132623766 @default.
• W2995538685 cites W2138592666 @default.
• W2995538685 cites W2143233396 @default.
• W2995538685 cites W2148216588 @default.
• W2995538685 cites W2149759976 @default.
• W2995538685 cites W2154882162 @default.
• W2995538685 cites W2156731130 @default.
• W2995538685 cites W2157098396 @default.
• W2995538685 cites W2164065545 @default.
• W2995538685 cites W2164489181 @default.
• W2995538685 cites W2172100406 @default.
• W2995538685 cites W2259423114 @default.
• W2995538685 cites W2291407818 @default.
• W2995538685 cites W2334539119 @default.
• W2995538685 cites W2583077266 @default.
• W2995538685 cites W2587853523 @default.
• W2995538685 cites W2605770782 @default.
• W2995538685 cites W2618110836 @default.
• W2995538685 cites W2745921792 @default.
• W2995538685 cites W2756138246 @default.
• W2995538685 cites W2803453391 @default.
• W2995538685 cites W2810169082 @default.
• W2995538685 cites W2885885677 @default.
• W2995538685 cites W2888601619 @default.
• W2995538685 cites W2894027454 @default.
• W2995538685 cites W2896579627 @default.
• W2995538685 cites W2908415217 @default.
• W2995538685 cites W4235029171 @default.
• W2995538685 doi "https://doi.org/10.1016/j.jhep.2019.12.009" @default.
• W2995538685 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31863794" @default.
• W2995538685 hasPublicationYear "2020" @default.
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