The transcription mechanismin coronaviruses is seemingly complicated as compared with the transcription mechanisms in other positive-strand RNA viruses, such as internal initiation and premature termination. In fact, in contrast to coronavirus and arterivirus sgmRNAs, subgenomic transcripts of other Nidovirales, such as toroviruses and roniviruses, do not have a common 5′ leader sequence.
In contrast to replication, coronavirus transcription includes a discontinuous step during the production of sgmRNA. This process, unique among known RNA viruses, is a hallmark of the order Nidovirales and ultimately generates a nested set of sgmRNAs that are 5′ and 3′ coterminal with the virus genome. These sgmRNAs all include at their 5′ end a common leader sequence, whose length ranges from 65 to 98 nt in different coronaviruses. This common leader sequence is present only once at the very 5′ end of the genome, which implies that sgmRNAs are synthesized by the fusion of noncontiguous sequences, the leader and the 5′ end of each mRNA coding sequence, called the body (B).
Like that of other positive-strand RNA viruses, coronavirus genome replication is a process of continuous synthesis that utilizes a full-length complementary negative-strand RNA as the template for the production of progeny virus genomes. The initiation of negative-strand synthesis involves access of the RNA-dependent RNA polymerase (RdRp) to the 3’terminus of the genome, promoted by 3′-end RNA sequences and structures. There is evidence that both 5′- and 3′- end RNA elements are required for the production of progeny positive-strand RNA from the intermediate negative-strand RNA, suggesting that interactions between the 5′ and 3′ ends of the genome contribute to replication.
Coronavirus RNA-dependent RNA synthesis includes two differentiated processes: genome replication, yielding multiple copies of genomic RNA (gRNA), and transcription of a collection of sgmRNAs that encode the viral structural and accessories proteins.
The 5′-proximal two-thirds of the coronavirus genome encodes the replicase gene, which contains two open reading frames, ORF1a and ORF1b. Translation of ORF1a yields polyprotein 1a (pp1a), and -1 ribosomal frameshifting allows translation of ORF1b to yield pp1ab. Together, these polyproteins are co- and posttranslationally processed into 16 nonstructural proteins (nsps), most of them driving viral genome replication and subgenomic mRNA (sgmRNA) synthesis. The 3′ third of the genome encodes the structural and accessory proteins, which vary in number among the different coronaviruses.
Two recent HCoVs, severe acute respiratory syndrome coronaviruses (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), emerged in 2002 and 2012, respectively, causing life-threathening disease in humans. In addition, novel animal coronaviruses, such as the porcine deltacoronavirus (PDCoV) and the porcine epidemic diarrhea virus (PEDV), have recently emerged, causing great economic loss in China and the United States
Coronaviruses are enveloped, positive-strand RNA viruses with genomes approximately 30 kb in length that belong to the family Coronaviridae in the order Nidovirales. Coronaviruses infect a wide variety of mammalian and avian species, in most cases causing respiratory and intestinal tract disease. Human coronaviruses (HCoVs), such as HCoV-OC43, HCoV-NL63 and HKU1, have long been recognized as major causes of the common cold.
