Classification, replication, and transcription of Nidovirales

Nidovirales is one order of RNA virus, with the largest single-stranded positive sense RNA genome enwrapped with membrane envelope. It comprises four families (Arterividae, Mesoniviridae, Roniviridae, and Coronaviridae) and has been circulating in humans and animals for almost one century, posing great threat to livestock and poultry，as well as to public health. Nidovirales shares similar life cycle: attachment to cell surface, entry, primary translation of replicases, viral RNA replication in cytoplasm, translation of viral proteins, virion assembly, budding, and release. The viral RNA synthesis is the critical step during infection, including genomic RNA (gRNA) replication and subgenomic mRNAs (sg mRNAs) transcription. gRNA replication requires the synthesis of a negative sense full-length RNA intermediate, while the sg mRNAs transcription involves the synthesis of a nested set of negative sense subgenomic intermediates by a discontinuous strategy. This RNA synthesis process is mediated by the viral replication/transcription complex (RTC), which consists of several enzymatic replicases derived from the polyprotein 1a and polyprotein 1ab and several cellular proteins. These replicases and host factors represent the optimal potential therapeutic targets. Hereby, we summarize the Nidovirales classification, associated diseases, "replication organelle," replication and transcription mechanisms, as well as related regulatory factors.