Abstract
Interferons inhibit viruses by inducing antiviral protein expression. One of the interferon-induced antiviral proteins, human Moloney leukemia virus 10 (MOV10), a superfamily 1 RNA helicase, has been shown to inhibit retroviruses and several RNA viruses. However, it remains undetermined whether MOV10 also inhibits DNA viruses, including hepatitis B virus (HBV). Here, we report that MOV10 dramatically reduces the levels of intracellular HBV DNA, resulting in significant inhibition of both the HBV experimental strain and the clinical isolates. Mechanistic experiments revealed that MOV10 interacts with HBV RNA and blocks the early step of viral reverse transcription, thereby impairing viral DNA synthesis, without affecting viral gene expression and pregenomic RNA encapsidation. Moreover, mutation of the helicase domain of MOV10 caused loss of binding to HBV RNA and of the anti-HBV activity. Together, our results indicate that MOV10 restricts HBV replication, insights that may open new avenues to the development of anti-HBV therapeutics.
Highlights
Interferons inhibit viruses by inducing antiviral protein expression
As the best-studied member of Hepadnaviridae, hepatitis B virus (HBV) has been classified as a pararetrovirus, because HBV DNA genome is generated by reverse transcription of the pregenomic RNA [4]
To determine HBV replication, we first measured the hepatitis B surface antigen (HBsAg) in the extracellular culture medium and found that Moloney leukemia virus 10 (MOV10) had no significant effect on the level of secreted HBsAg (Fig. 1B)
Summary
Interferons inhibit viruses by inducing antiviral protein expression. One of the interferon-induced antiviral proteins, human Moloney leukemia virus 10 (MOV10), a superfamily 1 RNA helicase, has been shown to inhibit retroviruses and several RNA viruses. Restricted HBV replication by reducing the level of intracellular viral DNA. To answer whether above findings were reproducible in other hepatoma cell lines, we performed the same experiments in Huh7 cells and observed similar inhibitory effect of MOV10 on HBV DNA replication (Supplementary Fig. 1A-G), which supports that MOV10-mediated inhibition of HBV is not cell-type specific.
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