Viruses with segmented ribonucleic acid genomes: multiplication of influenza versus reovirus.

More than 10 years ago it was proposed that the genome of influenza virus is made up of two or more single-stranded ribonucleic acid (RNA) segments rather than one continuous chain of covalently linked nucleotides (26, 60). The first evidence for such an unusual viral genome came from genetic studies. These were later supported by the finding that RNA extracted from influenza and other myxoviruses consists of a mixture of RNA fragments of molecular weight lower than that of the total viral RNA estimated chemically (3, 13, 38, 40a, 101, 109). It is now known that the double-stranded RNA genomes of reoviruses and similar animal and plant viruses are made up of distinct segments (47, 48, 70, 134, 135, 156). Recent studies of a variety of singlestranded RNA viruses including paramyxoviruses (Newcastle disease virus, NDV; reference 75), rhabdoviruses (vesicular stomatitis virus, VSV; references 67, 97, 104, 121), arboviruses (Sindbis virus; reference 36), and the RNA tumor viruses (4, 40) have shown that viral RNA genomes, or their complement in infected cells, are often found as subunits. Genetic and biochemical studies indicate that the RNA fragments are subgenomic structural units which have functional significance. For example, the recombination frequency predicted for an intact molecule of the size of the influenza genome is exceeded by several-fold experimentally, suggesting that the influenza RNA segments may be exchanged during virus multiplication in a manner analogous to the assortment of chromosomal linkage groups (143). In addition to a high frequency of recombination, influenza shares with reovirus other biological properties which are consistent with the organization of their genomes into functional segments. These include multiplicity reactivation (10, 94) and the formation of noninfectious particles deficient in one of the genome segments (27, 105, 110). For this review, the extensively studied myxoviruses (influenza) and reovirus groups have been selected as representative examples of viruses with segmented RNA genomes. Their composition and structure are compared, and the possible effects of genome fragmentation on virus multiplication are considered.