Heteroclite Subgenomic RNAs Are Produced in Porcine Reproductive and Respiratory Syndrome Virus Infection

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) was shown to produce atypical subgenomic RNAs that contain open reading frame 1a nucleotides and are present under a wide variety of culture conditions, including high and low multiplicities of infection, in simian and porcine host cells, and during infection with cell-adapted and wild-type PRRSV strains. Sequence analysis demonstrated that they are heterogeneous in 5′–3′ junction sequence and size and may code for different predicted fusion proteins. This is the first report of these novel RNAs in arteriviruses and we have termed them heteroclite (meaning “deviating from common forms or rules”) subgenomic RNAs. The unique properties of these subgenomic RNAs include (a) apparent association with normal virus infection and stability during serial passage, (b) packaging of heteroclite RNAs into virus-like particles, (c) short, heterogeneous sequences which may mediate the generation of these RNAs, (d) a primary structure which consists of the two genomic termini with one large internal deletion, and (e) little apparent interference with parental virus replication. These subgenomic RNAs may be critical to, or a necessary side product of, viral replication. The expression of these novel RNA species support the template-switching model of similarity-assisted RNA recombination. In summary, PRRSV readily undergoes nonhomologous RNA recombination to generate heteroclite subgenomic RNAs.