G Protein Pathway Suppressor 1 Promotes Influenza Virus Polymerase Activity by Activating the NF-κB Signaling Pathway

ABSTRACT 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 pathw...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tomoko Kuwahara, Seiya Yamayoshi, Takeshi Noda, Yoshihiro Kawaoka
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	COP9 signalosome GPS1 NF-kB influenza virus-host interactions Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e8bccb7061ea4ebc93a83bd9bff7ba52
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e8bccb7061ea4ebc93a83bd9bff7ba52
record_format	dspace
spelling	oai:doaj.org-article:e8bccb7061ea4ebc93a83bd9bff7ba522021-11-15T15:54:44ZG Protein Pathway Suppressor 1 Promotes Influenza Virus Polymerase Activity by Activating the NF-κB Signaling Pathway10.1128/mBio.02867-192150-7511https://doaj.org/article/e8bccb7061ea4ebc93a83bd9bff7ba522019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02867-19https://doaj.org/toc/2150-7511ABSTRACT 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.Tomoko KuwaharaSeiya YamayoshiTakeshi NodaYoshihiro KawaokaAmerican Society for MicrobiologyarticleCOP9 signalosomeGPS1NF-kBinfluenzavirus-host interactionsMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	COP9 signalosome GPS1 NF-kB influenza virus-host interactions Microbiology QR1-502
spellingShingle	COP9 signalosome GPS1 NF-kB influenza virus-host interactions Microbiology QR1-502 Tomoko Kuwahara Seiya Yamayoshi Takeshi Noda Yoshihiro Kawaoka G Protein Pathway Suppressor 1 Promotes Influenza Virus Polymerase Activity by Activating the NF-κB Signaling Pathway
description	ABSTRACT 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.
format	article
author	Tomoko Kuwahara Seiya Yamayoshi Takeshi Noda Yoshihiro Kawaoka
author_facet	Tomoko Kuwahara Seiya Yamayoshi Takeshi Noda Yoshihiro Kawaoka
author_sort	Tomoko Kuwahara
title	G Protein Pathway Suppressor 1 Promotes Influenza Virus Polymerase Activity by Activating the NF-κB Signaling Pathway
title_short	G Protein Pathway Suppressor 1 Promotes Influenza Virus Polymerase Activity by Activating the NF-κB Signaling Pathway
title_full	G Protein Pathway Suppressor 1 Promotes Influenza Virus Polymerase Activity by Activating the NF-κB Signaling Pathway
title_fullStr	G Protein Pathway Suppressor 1 Promotes Influenza Virus Polymerase Activity by Activating the NF-κB Signaling Pathway
title_full_unstemmed	G Protein Pathway Suppressor 1 Promotes Influenza Virus Polymerase Activity by Activating the NF-κB Signaling Pathway
title_sort	g protein pathway suppressor 1 promotes influenza virus polymerase activity by activating the nf-κb signaling pathway
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/e8bccb7061ea4ebc93a83bd9bff7ba52
work_keys_str_mv	AT tomokokuwahara gproteinpathwaysuppressor1promotesinfluenzaviruspolymeraseactivitybyactivatingthenfkbsignalingpathway AT seiyayamayoshi gproteinpathwaysuppressor1promotesinfluenzaviruspolymeraseactivitybyactivatingthenfkbsignalingpathway AT takeshinoda gproteinpathwaysuppressor1promotesinfluenzaviruspolymeraseactivitybyactivatingthenfkbsignalingpathway AT yoshihirokawaoka gproteinpathwaysuppressor1promotesinfluenzaviruspolymeraseactivitybyactivatingthenfkbsignalingpathway
_version_	1718427250887491584

G Protein Pathway Suppressor 1 Promotes Influenza Virus Polymerase Activity by Activating the NF-κB Signaling Pathway

Ejemplares similares