Expression and Replication of the Influenza Virus Genome

Abstract

The genome of influenza A viruses is composed of eight segments of negative polarity (see Chapter 1). In infected cells, these virion RNAs (vRNAs) are both transcribed into messenger RNAs (mRNAs) and replicated. The distinctive feature of influenza viral mRNA synthesis is that it is primed by 5′ capped (m⁷GpppNm-containing) fragments derived from newly synthesized host-cell RNA polymerase II transcripts (Bouloy et al., 1978, 1979; Krug et al.,1979; Plotch et al., 1979, 1981; Krug, 1981, 1983; Herz et al., 1981). The mRNA chains are elongated until a stretch of uridine residues is reached 17–22 nucleotides before the 5′ ends of the vRNAs, where transcription terminates and polyadenylate [poly(A)] is added to the mRNAs (Hay et al., 1977a; Robertson et al., 1981). For replication to occur, an alternative type of transcription is required that results in the production of full-length copies of the vRNAs. The full-length transcripts, or template RNAs, are initiated without a primer and are not terminated at the poly(A) site used during mRNA synthesis (Hay et al., 1977a, 1982). The second step in replication is the copying of the template RNAs into vRNAs. This synthesis also occurs without a primer, since the vRNAs contain 5′ triphosphorylated ends (Young and Content, 1971). The three types of virus-specific RNAs—mRNAs, template RNAs, and vRNAs— are all synthesized in the nucleus of infected cells (Herz et al., 1981; Jackson et al., 1982; Shapiro et al., 1987). During the early phase of infection, the synthesis of these three types of virus-specific RNAs is coupled (Hay et al., 1977a; G. L. Smith and Hay, 1982; Shapiro et al., 1987), whereas during the later phase of infection essentially only vRNAs are synthesized (Shapiro et al., 1987).