tetano
Editor, Senior Moderator
J Virol. 2015 Aug 26. pii: JVI.01487-15. [Epub ahead of print]
[h=1]A Nucleolar Protein, Ribosomal RNA Processing 1 Homolog B (RRP1B), Enhances the Recruitment of Cellular mRNA in Influenza Virus Transcription.[/h] Su WC[SUP]1[/SUP], Hsu SF[SUP]2[/SUP], Lee YY[SUP]2[/SUP], Jeng KS[SUP]3[/SUP], Lai MM[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A virus (IAV) undergoes RNA transcription by a unique capped mRNA-dependent transcription, which is carried out by the viral RNA-dependent RNA polymerase (RdRp), consisting of the viral PA, PB1 and PB2 proteins. But, how the viral RdRp utilizes cellular factors for viral transcription is not clear. Previously, we have conducted a genome-wide pooled shRNA screen to identify host factors important for influenza A virus replication. Ribosomal RNA processing 1 homolog B (RRP1B) was identified as one of the candidates. RRP1B is a nucleolar protein involved in ribosomal biogenesis. Upon IAV infection, part of RRP1B was translocated from the nucleolus to the nucleoplasm, where viral RNA synthesis likely takes place. The depletion of RRP1B significantly reduced IAV mRNA transcription in a mini-replicon assay and in virus-infected cells. Furthermore, we showed that RRP1B interacted with PB1 and PB2 of the RdRp and formed a coimmunoprecipitable complex with RdRp. The depletion of RRP1B reduced the amount of capped mRNA in the RdRp complex. Taken together, these findings indicate that RRP1B is a host factor essential for IAV transcription and provides a target for new antivirals.
[h=4]IMPORTANCE:[/h] Influenza virus is an important human pathogen which causes significant morbidity and mortality and threatens the human population with epidemics and pandemics every year. Due to high mutation rate of the virus, antiviral drugs targeting at viral proteins might ultimately lose their effectiveness. An alternative strategy that explores the genetic stability of host factors indispensable for influenza virus replication would thus be desirable. Here, we characterized the ribosomal RNA processing 1 homolog B (RRP1B) protein as an important cellular factor for influenza A viral transcription. We showed that silencing RRP1B hampered viral RNA-dependent RNA polymerase (RdRp) activity, which is responsible for viral transcription and replication. Furthermore, we reported that RRP1B is crucial for RdRp binding to cellular capped mRNA, which is a critical step of virus transcription. Our study not only provides a deeper understanding of influenza virus-host interplay but also suggests a potential target for antiviral drug development.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26311876 [PubMed - as supplied by publisher]
[h=1]A Nucleolar Protein, Ribosomal RNA Processing 1 Homolog B (RRP1B), Enhances the Recruitment of Cellular mRNA in Influenza Virus Transcription.[/h] Su WC[SUP]1[/SUP], Hsu SF[SUP]2[/SUP], Lee YY[SUP]2[/SUP], Jeng KS[SUP]3[/SUP], Lai MM[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A virus (IAV) undergoes RNA transcription by a unique capped mRNA-dependent transcription, which is carried out by the viral RNA-dependent RNA polymerase (RdRp), consisting of the viral PA, PB1 and PB2 proteins. But, how the viral RdRp utilizes cellular factors for viral transcription is not clear. Previously, we have conducted a genome-wide pooled shRNA screen to identify host factors important for influenza A virus replication. Ribosomal RNA processing 1 homolog B (RRP1B) was identified as one of the candidates. RRP1B is a nucleolar protein involved in ribosomal biogenesis. Upon IAV infection, part of RRP1B was translocated from the nucleolus to the nucleoplasm, where viral RNA synthesis likely takes place. The depletion of RRP1B significantly reduced IAV mRNA transcription in a mini-replicon assay and in virus-infected cells. Furthermore, we showed that RRP1B interacted with PB1 and PB2 of the RdRp and formed a coimmunoprecipitable complex with RdRp. The depletion of RRP1B reduced the amount of capped mRNA in the RdRp complex. Taken together, these findings indicate that RRP1B is a host factor essential for IAV transcription and provides a target for new antivirals.
[h=4]IMPORTANCE:[/h] Influenza virus is an important human pathogen which causes significant morbidity and mortality and threatens the human population with epidemics and pandemics every year. Due to high mutation rate of the virus, antiviral drugs targeting at viral proteins might ultimately lose their effectiveness. An alternative strategy that explores the genetic stability of host factors indispensable for influenza virus replication would thus be desirable. Here, we characterized the ribosomal RNA processing 1 homolog B (RRP1B) protein as an important cellular factor for influenza A viral transcription. We showed that silencing RRP1B hampered viral RNA-dependent RNA polymerase (RdRp) activity, which is responsible for viral transcription and replication. Furthermore, we reported that RRP1B is crucial for RdRp binding to cellular capped mRNA, which is a critical step of virus transcription. Our study not only provides a deeper understanding of influenza virus-host interplay but also suggests a potential target for antiviral drug development.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26311876 [PubMed - as supplied by publisher]