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Article: The NS1 protein of influenza A virus interacts with cellular processing bodies and stress granules through RNA-associated protein 55 (RAP55) during virus infection

TitleThe NS1 protein of influenza A virus interacts with cellular processing bodies and stress granules through RNA-associated protein 55 (RAP55) during virus infection
Authors
Issue Date2012
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal of Virology, 2012, v. 86 n. 23, p. 12695-12707 How to Cite?
AbstractThe nonstructural protein (NS1) of influenza A virus performs multiple functions in the virus life cycle. Proteomic screening for cellular proteins which interact with NS1 identified the cellular protein RAP55, which is one of the components of cellular processing bodies (P-bodies) and stress granules. To verify whether NS1 interacts with cellular P-bodies, interactions between NS1, RAP55, and other P-body-associated proteins (Ago1, Ago2, and DCP1a) were confirmed using coimmunoprecipitation and cellular colocalization assays. Overexpression of RAP55 induced RAP55-associated stress granule formation and suppressed virus replication. Knockdown of RAP55 with small interfering RNA (siRNA) or expression of a dominant-negative mutant RAP55 protein with defective interaction with P-bodies blocked NS1 colocalization to P-bodies in cells. Expression of NS1 inhibited RAP55 expression and formation of RAP55-associated P-bodies/stress granules. The viral nucleoprotein (NP) was found to be targeted to stress granules in the absence of NS1 but localized to P-bodies when NS1 was coexpressed. Restriction of virus replication via P-bodies occurred in the early phases of infection, as the number of RAP55-associated P-bodies in cells diminished over the course of virus infection. NS1 interaction with RAP55-associated P-bodies/stress granules was associated with RNA binding and mediated via a protein kinase R (PKR)-interacting viral element. Mutations introduced into either RNA binding sites (R38 and K41) or PKR interaction sites (I123, M124, K126, and N127) caused NS1 proteins to lose the ability to interact with RAP55 and to inhibit stress granules. These results reveal an interplay between virus and host during virus replication in which NP is targeted to P-bodies/stress granules while NS1 counteracts this host restriction mechanism.
Persistent Identifierhttp://hdl.handle.net/10722/189288
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMok, BWYen_US
dc.contributor.authorSong, Wen_US
dc.contributor.authorWang, Pen_US
dc.contributor.authorTai, Hen_US
dc.contributor.authorChen, Yen_US
dc.contributor.authorZheng, Men_US
dc.contributor.authorWen, Xen_US
dc.contributor.authorLau, SYen_US
dc.contributor.authorWu, WLen_US
dc.contributor.authorMatsumoto, Ken_US
dc.contributor.authorYuen, KYen_US
dc.contributor.authorChen, Hen_US
dc.date.accessioned2013-09-17T14:33:04Z-
dc.date.available2013-09-17T14:33:04Z-
dc.date.issued2012en_US
dc.identifier.citationJournal of Virology, 2012, v. 86 n. 23, p. 12695-12707en_US
dc.identifier.issn0022-538Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/189288-
dc.description.abstractThe nonstructural protein (NS1) of influenza A virus performs multiple functions in the virus life cycle. Proteomic screening for cellular proteins which interact with NS1 identified the cellular protein RAP55, which is one of the components of cellular processing bodies (P-bodies) and stress granules. To verify whether NS1 interacts with cellular P-bodies, interactions between NS1, RAP55, and other P-body-associated proteins (Ago1, Ago2, and DCP1a) were confirmed using coimmunoprecipitation and cellular colocalization assays. Overexpression of RAP55 induced RAP55-associated stress granule formation and suppressed virus replication. Knockdown of RAP55 with small interfering RNA (siRNA) or expression of a dominant-negative mutant RAP55 protein with defective interaction with P-bodies blocked NS1 colocalization to P-bodies in cells. Expression of NS1 inhibited RAP55 expression and formation of RAP55-associated P-bodies/stress granules. The viral nucleoprotein (NP) was found to be targeted to stress granules in the absence of NS1 but localized to P-bodies when NS1 was coexpressed. Restriction of virus replication via P-bodies occurred in the early phases of infection, as the number of RAP55-associated P-bodies in cells diminished over the course of virus infection. NS1 interaction with RAP55-associated P-bodies/stress granules was associated with RNA binding and mediated via a protein kinase R (PKR)-interacting viral element. Mutations introduced into either RNA binding sites (R38 and K41) or PKR interaction sites (I123, M124, K126, and N127) caused NS1 proteins to lose the ability to interact with RAP55 and to inhibit stress granules. These results reveal an interplay between virus and host during virus replication in which NP is targeted to P-bodies/stress granules while NS1 counteracts this host restriction mechanism.en_US
dc.languageengen_US
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/en_US
dc.relation.ispartofJournal of Virologyen_US
dc.rightsJournal of Virology. Copyright © American Society for Microbiology.en_US
dc.rightsCopyright © American Society for Microbiology, [insert journal name, volume number, page numbers, and year]en_US
dc.subject.meshCytoplasmic Granules - metabolismen_US
dc.subject.meshInfluenza A Virus, H1N1 Subtype - metabolism - physiologyen_US
dc.subject.meshRibonucleoproteins - genetics - metabolismen_US
dc.subject.meshViral Nonstructural Proteins - metabolismen_US
dc.subject.meshVirus Replication - physiologyen_US
dc.titleThe NS1 protein of influenza A virus interacts with cellular processing bodies and stress granules through RNA-associated protein 55 (RAP55) during virus infectionen_US
dc.typeArticleen_US
dc.identifier.emailMok, BWY: bobomok@hkucc.hku.hken_US
dc.identifier.emailSong, W: wjsong@hkucc.hku.hken_US
dc.identifier.emailWang, P: puiwang@hkucc.hku.hken_US
dc.identifier.emailTai, H: bart@hkucc.hku.hken_US
dc.identifier.emailLau, SY: sylau926@hkucc.hku.hken_US
dc.identifier.emailWu, WL: hazelwu@hkucc.hku.hken_US
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hken_US
dc.identifier.emailChen, H: hlchen@hku.hken_US
dc.identifier.authorityYuen, KY=rp00366en_US
dc.identifier.authorityChen, H=rp00383en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1128/JVI.00647-12en_US
dc.identifier.pmid22973032en_US
dc.identifier.pmcidPMC3497642en_US
dc.identifier.hkuros221007en_US
dc.identifier.volume86en_US
dc.identifier.issue23en_US
dc.identifier.spage12695en_US
dc.identifier.epage12707en_US
dc.identifier.isiWOS:000310585300022-
dc.publisher.placeUnited Statesen_US

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