Identification of the cap binding protein of influenza virus

Blaas, Dieter; Patzelt, Erik; Kuechler, Ernst

doi:10.1093/nar/10.15.4803

Cited by 138 publications

(91 citation statements)

References 16 publications

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“…For instance, in¯uenza virus mutants carrying mutations in the PB2 gene show defect in capped RNA cleavage (Ulmanen et al 1983). Uniformly radiolabelled cap RNA could be cross-linked to the PB2 protein Blaas et al 1982;Penn et al 1982). The recombinant baculovirus-expressed PB2 alone is able to bind the cap structure in an isolated state (Shi et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Two separate sequences of PB2 subunit constitute the RNA cap‐binding site of influenza virus RNA polymerase

1999

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Background: In¯uenza virus RNA polymerase with the subunit composition of PB1-PB2-PA is a unique multifunctional enzyme with the activities of both synthesis and cleavage of RNA, and is involved in both transcription and replication of the RNA genome. Transcription is initiated by using capped RNA fragments, which are generated after cleavage of host cell mRNA by the RNA polymeraseassociated capped RNA endonuclease. To identify the RNA cap 1-binding site on the RNA polymerase, viral ribonucleoprotein (RNP) cores were subjected to UV-crosslinking with RNA which was labelled with 32 P only at the cap-1 structure.

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Section: Introductionmentioning

confidence: 99%

Two separate sequences of PB2 subunit constitute the RNA cap‐binding site of influenza virus RNA polymerase

1999

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“…It contains motifs typical of an RNA-dependent RNA polymerase (Poch et al, 1990) that are essential for its biological activity (Biswas & Nayak, 1994). The PB2 subunit has been shown to interact with cap 1 structures (Blaas et al, 1982 ;Ulmanen et al, 1981), and its possible involvement in the endonucleolytic cleavage of the host cellular mRNA precursors has been reported (Hagen et al, 1994 ;Licheng et al, 1995). The experiments carried out with ts virus mutants with defects in the PA gene have shown that, under these conditions, there is a defect in viral RNA replication but not in viral transcription (Mahy, 1983), although the mechanism for this is not known.…”

Section: Introductionmentioning

confidence: 99%

The PA influenza virus polymerase subunit is a phosphorylated protein.

Sanz‐Ezquerro

Santarén

Sierra

et al. 1998

Journal of General Virology

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The induction of proteolysis by expression of the influenza virus PA polymerase subunit is the only biochemical activity ascribed to this protein. In the course of studying viral protein synthesis by twodimensional gel electrophoresis, we observed the existence of several PA isoforms with different isoelectric points. These isoforms were also present when the PA gene was singly expressed in three different expression systems, indicating that a cellular activity is responsible for its post-translational modification. In vivo labelling with [ 32 P]orthophosphate, followed by two-dimensional gel electrophoresis, clearly demonstrated the incorporation of phosphate into the PA molecule. Phosphoserine

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“…Subsequently, vRNP is translocated to the nucleus for transcription and replication of the influenza virus genome, which are both carried out by RdRp (4). IAV RNA transcription undergoes a unique cap-snatching process, in which PB2 first binds to the 5= cap of the host mRNA (5,6), PA subsequently cleaves the host mRNA to produce capped RNA fragments with lengths of 10 to 13 nucleotides (7), and PB1 finally elongates the viral mRNA by RNA polymerization using the viral negative-sense RNA as a template (8). Of note, production of the primer RNA requires PB1 binding to the 5= and 3= end sequences of vRNA (9).…”

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confidence: 99%

A Nucleolar Protein, Ribosomal RNA Processing 1 Homolog B (RRP1B), Enhances the Recruitment of Cellular mRNA in Influenza Virus Transcription

Hsu

Lee

et al. 2015

J Virol

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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. However, how the viral RdRp utilizes cellular factors for virus transcription is not clear. Previously, we conducted a genome-wide pooled short hairpin RNA (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 minireplicon 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 provide a target for new antivirals. IMPORTANCEInfluenza virus is an important human pathogen that causes significant morbidity and mortality and threatens the human population with epidemics and pandemics every year. Due to the high mutation rate of the virus, antiviral drugs targeting 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 rRNA processing 1 homolog B (RRP1B) protein as an important cellular factor for influenza A virus transcription. We showed that silencing RRP1B hampered viral RNA-dependent RNA polymerase (RdRp) activity, which is responsible for virus 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.

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Identification of the cap binding protein of influenza virus

Cited by 138 publications

References 16 publications

Two separate sequences of PB2 subunit constitute the RNA cap‐binding site of influenza virus RNA polymerase

Two separate sequences of PB2 subunit constitute the RNA cap‐binding site of influenza virus RNA polymerase

The PA influenza virus polymerase subunit is a phosphorylated protein.

A Nucleolar Protein, Ribosomal RNA Processing 1 Homolog B (RRP1B), Enhances the Recruitment of Cellular mRNA in Influenza Virus Transcription

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