Involvement of the nucleus in flu virus replication

Despite some general similarities with VSV in transcription of the genomic negative-sense strands of influenza virus to generate mRNA, there are important differences in the overall replication process. A major difference is that influenza virus mRNA synthesis and genome replication require the cell's nucleus. There are two readily apparent reasons for this. First, flu replicase cannot cap mRNA; therefore, each flu virus mRNA generated has to use a cellular mRNA cap as a "primer." Synthesis of each flu virus mRNA begins with a short stretch of cellular mRNA with its 5' methylated cap. This cap snatching or stealing is a form of intermolecular splicing, and is accomplished by the flu virus replication-transcription complex as it associates with actively transcribed cellular mRNA. Thus, the virus inhibits cellular mRNA transport and protein synthesis, but not initiation of transcription.

Second, influenza A virus utilizes the intramolecular splicing machinery of the host cell's nucleus. Two of the RNPs of the flu virus express mRNA precursors that are spliced in the nucleus. Each of these gene segments, then, can encode two related proteins. This splicing takes place via cellular spliceosomes in a manner identical to that described in Chapter 13, Part III. The result of the splices is that two segments of the viral genome actually generate four distinct mRNAs. Thus, with influenza A, the eight flu virus negative-sense genomic segments encode 10 specific mRNAs that are translated into distinct viral proteins.

Influenza A virus

Neuraminidase

Influenza A virus

Neuraminidase

Fig. 15.5 The structure of influenza virus A. The virion is about 120 nm in diameter, and the genome is made up of eight helical nucleocapsid segments that total about 13,600 nucleotides of negative-sense strand RNA. The virus requires the nucleus for replication. Although these virions also exhibit neuraminidase and hemagglutinin, the glycoproteins responsible are separate.

Nucleoprotein-RNA complexes

Fig. 15.5 The structure of influenza virus A. The virion is about 120 nm in diameter, and the genome is made up of eight helical nucleocapsid segments that total about 13,600 nucleotides of negative-sense strand RNA. The virus requires the nucleus for replication. Although these virions also exhibit neuraminidase and hemagglutinin, the glycoproteins responsible are separate.

Nucleoprotein-RNA complexes

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