tetano
Editor, Senior Moderator
MBio. 2019 Dec 17;10(6). pii: e02867-19. doi: 10.1128/mBio.02867-19. [h=1]G Protein Pathway Suppressor 1 Promotes Influenza Virus Polymerase Activity by Activating the NF-κB Signaling Pathway.[/h]
Kuwahara T[SUP]1,[/SUP][SUP]2[/SUP], Yamayoshi S[SUP]2[/SUP], Noda T[SUP]2,[/SUP][SUP]3[/SUP], Kawaoka Y[SUP]4,[/SUP][SUP]5,[/SUP][SUP]6[/SUP].
[h=3]Author information[/h] 1 Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan. 2 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. 3 Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan. 4 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan kawaoka@ims.u-tokyo.ac.jp. 5 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan. 6 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
[h=3]Abstract[/h] Influenza virus relies heavily on cellular machinery to replicate in host cells. Therefore, to better understand the influenza virus life cycle, it is important to identify which host proteins are involved and how they function in virus replication. Previously, we identified G protein pathway suppressor 1 (GPS1) to be a matrix protein 2 (M2)-interacting host protein. GPS1 is a component of the COP9 signalosome, which regulates the NF-κB signaling pathway. Here, we found that the downregulation of GPS1 expression reduced influenza virus replication by more than 2 log units. Although GPS1 was not involved in the early and late stages of virus replication, such as viral entry, uncoating, assembly, or budding, we found that viral polymerase activity was impaired in GPS1-downregulated cells. Moreover, our results suggest that M2 activates the NF-κB signaling pathway in a GPS1-dependent manner and that activation of NF-κB signaling leads to the upregulation of influenza virus polymerase activity. Our findings indicate that GPS1 is involved in the transcription and replication of influenza virus genomic RNA through the activation of the NF-κB signaling pathway.IMPORTANCE In the present study, we identified G protein pathway suppressor 1 (GPS1) to be a host cellular protein that is important for influenza virus replication. We also found that GPS1 plays a role in viral genome transcription through the NF-κB signaling pathway. Moreover, downregulation of GPS1 also affected the growth of vesicular stomatitis virus. Therefore, GPS1 may be a host target for antiviral drugs against influenza virus and possibly other viruses.
Copyright ? 2019 Kuwahara et al.
[h=4]KEYWORDS:[/h] COP9 signalosome; GPS1; NF-kB; influenza; virus-host interactions
PMID: 31848286 DOI: 10.1128/mBio.02867-19
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Kuwahara T[SUP]1,[/SUP][SUP]2[/SUP], Yamayoshi S[SUP]2[/SUP], Noda T[SUP]2,[/SUP][SUP]3[/SUP], Kawaoka Y[SUP]4,[/SUP][SUP]5,[/SUP][SUP]6[/SUP].
[h=3]Author information[/h] 1 Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan. 2 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. 3 Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan. 4 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan kawaoka@ims.u-tokyo.ac.jp. 5 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan. 6 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
[h=3]Abstract[/h] Influenza virus relies heavily on cellular machinery to replicate in host cells. Therefore, to better understand the influenza virus life cycle, it is important to identify which host proteins are involved and how they function in virus replication. Previously, we identified G protein pathway suppressor 1 (GPS1) to be a matrix protein 2 (M2)-interacting host protein. GPS1 is a component of the COP9 signalosome, which regulates the NF-κB signaling pathway. Here, we found that the downregulation of GPS1 expression reduced influenza virus replication by more than 2 log units. Although GPS1 was not involved in the early and late stages of virus replication, such as viral entry, uncoating, assembly, or budding, we found that viral polymerase activity was impaired in GPS1-downregulated cells. Moreover, our results suggest that M2 activates the NF-κB signaling pathway in a GPS1-dependent manner and that activation of NF-κB signaling leads to the upregulation of influenza virus polymerase activity. Our findings indicate that GPS1 is involved in the transcription and replication of influenza virus genomic RNA through the activation of the NF-κB signaling pathway.IMPORTANCE In the present study, we identified G protein pathway suppressor 1 (GPS1) to be a host cellular protein that is important for influenza virus replication. We also found that GPS1 plays a role in viral genome transcription through the NF-κB signaling pathway. Moreover, downregulation of GPS1 also affected the growth of vesicular stomatitis virus. Therefore, GPS1 may be a host target for antiviral drugs against influenza virus and possibly other viruses.
Copyright ? 2019 Kuwahara et al.
[h=4]KEYWORDS:[/h] COP9 signalosome; GPS1; NF-kB; influenza; virus-host interactions
PMID: 31848286 DOI: 10.1128/mBio.02867-19
Free full text