A novel human coronavirus: Middle East respiratory syndrome human coronavirus

Geng, HeYuan; Tan, WenJie

Coronaviruses are the largest known enveloped positivestranded RNA viruses, ranging in length from 26 to 32 kb. A terminal cap at the 5′ end is followed by a leader sequence of 65-98 nucleotides (nt), and an untranslated region (UTR) of 200-600 nt. The leader sequence is present at the 5′ end of all subgenomic mRNAs. Another UTR of 200-500 nt is at the 3′ end of the genome followed by a poly(A) tail of variable length. 5′-UTR contains the signals for genome replication, transcription and encapsidation, whereas the 3′-UTR contains transcription termination signals [14] . At the 5′ end nearly two-thirds of the genome encode two large overlapping open reading frames (ORF), ORF1a and ORF1b. When the coronavirus enters the host cell, ORF1a and ORF1b are first translated into two large polyproteins, pp1a and pp1ab. Production of pp1ab requires a programmed 1 ribosomal frameshift between the ORF1a and ORF1b junction. These polyproteins are processed autoproteolytically and subsequently form a transcriptionreplication complex [15] . About one-third of the genome at the 3′ end encodes four structural proteins, named the spike protein (S), envelop protein (E), small membrane protein (M) and the nucleocapsid protein (N). These structural proteins are present in all known coronaviruses. The general genome organisation of coronaviruses is as follows: 5′-UTR-1a/1b-spike (S)-envelope (E)-membrane (M)-nucleocapsid (N)-3′-UTR. Among the structural proteins are several small group-specific ORFs, which differ markedly in number and gene order, but are conserved within the same group. These small ORFs are dispensable for viral replication in vitro, but determine viral pathogenesis [16] .