Host Protein Moloney Leukemia Virus 10 (MOV10) Acts as a Restriction Factor of Influenza A Virus by Inhibiting the Nuclear Import of the Viral Nucleoprotein
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Host Protein Moloney Leukemia Virus 10 (MOV10) Acts as a Restriction Factor of Influenza A Virus by Inhibiting the Nuclear Import of the Viral Nucleoprotein. / Zhang, Junsong; Huang, Feng; Tan, Likai; Bai, Chuan; Chen, Bing; Liu, Jun; Liang, Juanran; Liu, Chao; Zhang, Shaoying; Lu, Gen; Chen, Yuan; Zhang, Hui.
In: J VIROL, Vol. 90, No. 8, 04.2016, p. 3966-3980.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Host Protein Moloney Leukemia Virus 10 (MOV10) Acts as a Restriction Factor of Influenza A Virus by Inhibiting the Nuclear Import of the Viral Nucleoprotein
AU - Zhang, Junsong
AU - Huang, Feng
AU - Tan, Likai
AU - Bai, Chuan
AU - Chen, Bing
AU - Liu, Jun
AU - Liang, Juanran
AU - Liu, Chao
AU - Zhang, Shaoying
AU - Lu, Gen
AU - Chen, Yuan
AU - Zhang, Hui
N1 - Copyright © 2016, American Society for Microbiology. All Rights Reserved.
PY - 2016/4
Y1 - 2016/4
N2 - UNLABELLED: 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 that its function can be affected by host factors. In our study, we identified host protein Moloney leukemia virus 10 (MOV10) as an inhibitor of 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 of 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.IMPORTANCE: The interaction between the influenza virus 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 the influenza virus 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 virus transmission and pathogenicity. Importantly, as an 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.
AB - UNLABELLED: 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 that its function can be affected by host factors. In our study, we identified host protein Moloney leukemia virus 10 (MOV10) as an inhibitor of 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 of 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.IMPORTANCE: The interaction between the influenza virus 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 the influenza virus 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 virus transmission and pathogenicity. Importantly, as an 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.
KW - Active Transport, Cell Nucleus
KW - Animals
KW - Cell Line, Tumor
KW - Dogs
KW - Enzyme Inhibitors/metabolism
KW - HEK293 Cells
KW - Humans
KW - Influenza A virus/physiology
KW - Madin Darby Canine Kidney Cells
KW - Nucleocapsid Proteins
KW - Protein Binding
KW - RNA Helicases/metabolism
KW - RNA-Binding Proteins/antagonists & inhibitors
KW - RNA-Dependent RNA Polymerase/antagonists & inhibitors
KW - Viral Core Proteins/antagonists & inhibitors
U2 - 10.1128/JVI.03137-15
DO - 10.1128/JVI.03137-15
M3 - SCORING: Journal article
C2 - 26842467
VL - 90
SP - 3966
EP - 3980
JO - J VIROL
JF - J VIROL
SN - 0022-538X
IS - 8
ER -
