tetano
Editor, Senior Moderator
J Virol. 2016 Feb 3. pii: JVI.03137-15. [Epub ahead of print]
[h=1]MOV10 is a Restriction Factor of Influenza A Virus by Inhibiting the Nuclear Import of the Viral Nucleoprotein.[/h] Zhang J[SUP]1[/SUP], Huang F[SUP]2[/SUP], Tan L[SUP]3[/SUP], Bai C[SUP]3[/SUP], Chen B[SUP]3[/SUP], Liu J[SUP]3[/SUP], Liang J[SUP]3[/SUP], Liu C[SUP]3[/SUP], Zhang S[SUP]3[/SUP], Lu G[SUP]4[/SUP], Chen Y[SUP]5[/SUP], Zhang H[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The viral ribonucleoprotein (vRNP) complex of influenza A viruses (IAVs) contains an RNA-dependent RNA polymerase complex (RdRp) and nucleoprotein (NP), and is the functional unit for viral RNA transcription and replication. The vRNP complex is an important determinant of virus pathogenicity and host adaptation, implying its function can be affected by host factors. In our study, we identified host protein Moloney leukemia virus 10 (MOV10) as an inhibitor for IAV replication, since depletion of MOV10 resulted in a significant increase in virus yield. MOV10 inhibited the polymerase activity in a minigenome system through RNA-mediated interaction with the NP subunit of vRNP complex. Importantly, we found that the interaction between MOV10 and NP prevented the binding of NP to importin-α, resulting in the retention of NP in the cytoplasm. Both the binding of MOV10 to NP and its inhibitory effect on polymerase activity were independent on its helicase activity. These results suggest that MOV10 acts as an anti-influenza virus factor through specifically inhibiting the nuclear transportation of NP and subsequently inhibiting the function of the vRNP complex.
[h=4]IMPORTANCE:[/h] The interaction between the influenza vRNP complex and host factors is a major determinant of viral tropism and pathogenicity. Our study identified MOV10 as a novel host restriction factor for influenza viral life cycle since it inhibited the viral growth rate. Conversely, importin-α has been shown as a determinant for influenza tropism and a positive regulator for viral polymerase activity in mammalian cells, but not in avian cells. MOV10 disrupted the interaction between NP and importin-α, suggesting that MOV10 could also be an important host factor for influenza viral transmission and pathogenicity. Importantly, as a member of interferon (IFN)-inducible protein, MOV10 exerted a novel mechanism for IFNs to inhibit the replication of influenza viruses. Furthermore, our study potentially provides a new drug design strategy, the use of molecules that mimic the antiviral mechanism of MOV10.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 26842467 [PubMed - as supplied by publisher]
[h=1]MOV10 is a Restriction Factor of Influenza A Virus by Inhibiting the Nuclear Import of the Viral Nucleoprotein.[/h] Zhang J[SUP]1[/SUP], Huang F[SUP]2[/SUP], Tan L[SUP]3[/SUP], Bai C[SUP]3[/SUP], Chen B[SUP]3[/SUP], Liu J[SUP]3[/SUP], Liang J[SUP]3[/SUP], Liu C[SUP]3[/SUP], Zhang S[SUP]3[/SUP], Lu G[SUP]4[/SUP], Chen Y[SUP]5[/SUP], Zhang H[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The viral ribonucleoprotein (vRNP) complex of influenza A viruses (IAVs) contains an RNA-dependent RNA polymerase complex (RdRp) and nucleoprotein (NP), and is the functional unit for viral RNA transcription and replication. The vRNP complex is an important determinant of virus pathogenicity and host adaptation, implying its function can be affected by host factors. In our study, we identified host protein Moloney leukemia virus 10 (MOV10) as an inhibitor for IAV replication, since depletion of MOV10 resulted in a significant increase in virus yield. MOV10 inhibited the polymerase activity in a minigenome system through RNA-mediated interaction with the NP subunit of vRNP complex. Importantly, we found that the interaction between MOV10 and NP prevented the binding of NP to importin-α, resulting in the retention of NP in the cytoplasm. Both the binding of MOV10 to NP and its inhibitory effect on polymerase activity were independent on its helicase activity. These results suggest that MOV10 acts as an anti-influenza virus factor through specifically inhibiting the nuclear transportation of NP and subsequently inhibiting the function of the vRNP complex.
[h=4]IMPORTANCE:[/h] The interaction between the influenza vRNP complex and host factors is a major determinant of viral tropism and pathogenicity. Our study identified MOV10 as a novel host restriction factor for influenza viral life cycle since it inhibited the viral growth rate. Conversely, importin-α has been shown as a determinant for influenza tropism and a positive regulator for viral polymerase activity in mammalian cells, but not in avian cells. MOV10 disrupted the interaction between NP and importin-α, suggesting that MOV10 could also be an important host factor for influenza viral transmission and pathogenicity. Importantly, as a member of interferon (IFN)-inducible protein, MOV10 exerted a novel mechanism for IFNs to inhibit the replication of influenza viruses. Furthermore, our study potentially provides a new drug design strategy, the use of molecules that mimic the antiviral mechanism of MOV10.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 26842467 [PubMed - as supplied by publisher]