Mutants of Influenza Virus

Mahy, Brian W. J.

doi:10.1007/978-3-7091-8706-7_7

Cited by 75 publications

(64 citation statements)

References 245 publications

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“…The phenotype of classical temperature-sensitive mutants suggested that PB1 is responsible for all RNA synthesis, while PA and PB2 would be involved in RNA replication and transcription, respectively (reviewed in ref. 44). Site-directed mutations verified these hypotheses [45][46][47] but also showed that PB2 has a role in replication 48 and PA is involved in cap-snatching.…”

Section: The Polymerase Complexmentioning

confidence: 99%

The influenza virus RNA synthesis machine

et al. 2011

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Section: The Polymerase Complexmentioning

confidence: 99%

The influenza virus RNA synthesis machine

et al. 2011

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“…These polymerase subunits are responsible for the synthesis of the three classes of viral RNA molecules : (i) mRNAs that are capped and polyadenylated ; (ii) virion RNAs found in the viral particle (vRNA) ; and (iii) cRNAs that serve as templates for the synthesis of vRNA (Krug, 1989 ;Mahy, 1983). Different studies have characterized some of the roles of each subunit in the polymerase complex.…”

Section: Introductionmentioning

confidence: 99%

“…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. We have found that when PA is expressed from cDNA, it induces a generalized proteolysis of viral and cellular co-expressed proteins (Sanz-Ezquerro et al, 1995).…”

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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“…In addition, mutations in the N-terminal region of the PB2 subunit alter the viral replication capacity but not the transcription activity of RNPs (26). The PA subunit has been associated with the replication activity of the polymerase (27,28). However, a PA mutation has been reported that abolishes cap-snatching but not RNA replication (29).…”

mentioning

confidence: 99%

3D structure of the influenza virus polymerase complex: Localization of subunit domains

Area‐Gómez

Martín‐Benito

Gastaminza

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

115

112

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The 3D structure of the influenza virus polymerase complex was determined by electron microscopy and image processing of recombinant ribonucleoproteins (RNPs). The RNPs were generated by in vivo amplification using cDNAs of the three polymerase subunits, the nucleoprotein, and a model virus-associated RNA containing 248 nt. The polymerase structure obtained is very compact, with no apparent boundaries among subunits. The position of specific regions of the PB1, PB2, and PA subunits was determined by 3D reconstruction of either RNP-mAb complexes or tagged RNPs. This structural model is available for the polymerase of a negative-stranded RNA virus and provides a general delineation of the complex and its interaction with the template-associated nucleoprotein monomers in the RNP.M any viruses contain RNA as genetic material and use RNA-dependent RNA polymerases as enzymes for replication and transcription. The atomic structures of several viral RNA (vRNA)-dependent RNA polymerases from positive-and double-stranded RNA viruses are available (1-6). These proteins show little sequence homology with other DNA-dependent polymerases but contain specific sequence motifs shared with other polymerases (7). They show a typical right-hand fold that includes the thumb, finger, and palm domains, the last of which contains the conserved sequence motifs involved in polymerase catalysis. These polymerases are medium-size proteins that show activity in vitro, although viral replication and transcription in vivo are carried out by polymerase-containing macrocomplexes. In these, other viral and cellular factors contribute to the efficiency and regulation of the polymerase or to the localization of the RNA synthetic machinery in the infected cell (reviewed in ref. 8).The situation in negative-strand viruses (NSVs) is different. The templates for transcription and replication are ribonucleoproteins (RNPs) in which the negative-stranded RNA is complexed with the nucleoprotein (NP) and associated to the polymerase. In the NSVs, the polymerase is a very large protein, the L protein (Ϸ 250 kDa, except in the Orthomyxoviridae), which consists of a heterotrimer of similar aggregate size. The replication intermediates are RNPs similar to virion RNPs but containing positive-stranded RNA. Other viral proteins, such as the P protein for nonsegmented NSVs, and cellular factors are essential for transcription or replication of NSV RNPs. As a consequence of this complexity, very little structural information is available on NSV polymerases.Within the NSVs, influenza A viruses are distinct in having a segmented genome and replicating in the cell nucleus (9). Their genome consists of eight RNPs that are transcribed and replicated by the viral polymerase, a heterotrimer composed by the PB1, PB2, and PA subunits (10, 11). Replication of vRNA involves de novo initiation of nascent RNA chains, whereas initiation of mRNA synthesis requires the generation of capped primers from cellular heterogeneous nuclear RNAs by a capstealing mechanism (12). Transcript...

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Mutants of Influenza Virus

Cited by 75 publications

References 245 publications

The influenza virus RNA synthesis machine

The influenza virus RNA synthesis machine

The PA influenza virus polymerase subunit is a phosphorylated protein.

3D structure of the influenza virus polymerase complex: Localization of subunit domains

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