Molecular Advances in Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV)

Chow, Ken Yan Ching; Hon, Chung Chau; Hui, Raymond Kin Hi; Wong, Raymond Tsz Yeung; Yip, Chi Wai; Zeng, Fanya; Leung, Frederick Chi Ching

Based on the antigenic cross reactivity and genome characteristics, existing coronaviruses are generally classified into three subgroups (40 ) . All coronaviruses share a very similar organization in their functional and structural genes, but the arrangement of the so-called non-essential genes is remarkably different among the subgroups. Group 1 coronaviruses are mainly characterized by the presence of ORFs following the N gene. Group 2 coronaviruses have two additional ORFs, non-structural protein 2 (ns2) and HE gene, located between ORF 1b and the S gene. Only group 3 species have ORFs located between the M and N gene, and a conserved stem-loop motif s2m at their 3 UTR (Figure 1 ). Accessory ORFs are found between the S and E genes in all of the subgroups. However, these accessory ORFs within the S-E intergenic region do not seem to be homologous between the subgroups, though they are conserved within subgroups. The rate of evolution of these accessory genes is obviously higher than that of the essential genes, which provides an alternative to access the phylogeny of the coronavirus family. The names of the group-specific accessory ORFs were unified and denoted on the top of the corresponding subgroup ORFs. The X (black cross) represents the absence of ORFs within the region. Genome organization and accessory ORFs of these CoVs were confirmed except for the n2s of PHEV. All the accessory genes are group-specific and highly diverged within subgroups, particular within the S−E intergenic region. SARS-CoV has a very similar genome structure with group 3 CoVs, with two ORFs located between M and N gene, and a conserved stem-loop motif s2m at their 3 UTR. Although the ORF 5a/5b of group 3 CoVs and ORF 5/6 of SARS-CoV are in homologous location, they do not have any significant sequence homology. Based on the confirmed ORFs of the SARS-CoV described above, a comparison of all homologous accessory and essential ORFs of known coronaviruses with the novel SARS-CoV is shown in Figure 1 . From the results, it does not seem that the coding regions are a consequence of a newly occurring recombination event between any of the existing known coronaviruses, similar to the conclusion made by Holmes (9 ) . Interestingly, the SARS-CoV genome has a very similar organization to that of group 3 avian coronaviruses (IBV and TCV), with the presence of three ORFs within the M-N intergenic region, two ORFs spanning between the S and E genes (65 ) , and a stem-loop motif s2m in 3 UTR. The presence of s2m and the finding that the 3 fragment of SARS-CoV RDRP clustered into group 3 in the phylogenetic analysis (39 ) suggest that the avian coronaviruses and the SARS-CoV might share a common ancestor which gained the s2m from a single RNA horizontal transfer event from a non-related virus family, as the astroviruses did (39 , 66 ) . Another possibility, that a common coronavirus ancestor had once gained the motif but subsequently lost it, except the group 3 and SARS-CoV, cannot of course be excluded. Pairwise sequence homology search among the accessory ORFs at the S-E intergenic region of the SARS-CoV and all other coronaviruses shows no significant sequence homology (12 -14 ) but they are homologous within subgroups. The ORF 5a/5b of group 3 coronaviruses and ORFs 6-8 of the SARS-CoV are in a homologous location, but they do not have any significant sequence homology. The above results imply that, although the SARS-CoV and group 3 coronaviruses have a very simila