Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage.
The genome organization and expression strategy of the newly identified severe acute respiratory syndrome coronavirus (SARS-CoV) were predicted using recently published genome sequences. Fourteen putative open reading frames were identified, 12 of which were predicted to be expressed from a nested set of eight subgenomic mRNAs. The synthesis of these mRNAs in SARS-CoV-infected cells was confirmed experimentally. The 4382- and 7073 amino acid residue SARS-CoV replicase polyproteins are predicted to be cleaved into 16 subunits by two viral proteinases (bringing the total number of SARS-CoV proteins to 28). A phylogenetic analysis of the replicase gene, using a distantly related torovirus as an outgroup, demonstrated that, despite a number of unique features, SARS-CoV is most closely related to group 2 coronaviruses. Distant homologs of cellular RNA processing enzymes were identified in group 2 coronaviruses, with four of them being conserved in SARS-CoV. These newly recognized viral enzymes place the mechanism of coronavirus RNA synthesis in a completely new perspective. Furthermore, together with previously described viral enzymes, they will be important targets for the design of antiviral strategies aimed at controlling the further spread of SARS-CoV.
Snijder
Eric J
EJ
Department of Medical Microbiology, Leiden University Medical Center, Room L4-34, Albinusdreef 2, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Bredenbeek
Peter J
PJ
Dobbe
Jessika C
JC
Thiel
Volker
V
Ziebuhr
John
J
Poon
Leo L M
LL
Guan
Yi
Y
Rozanov
Mikhail
M
Spaan
Willy J M
WJ
Gorbalenya
Alexander E
AE
D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D017934:Coronavirus / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D016679:Genome, Viral; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D020543:Proteome; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014709:Vero Cells; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D021122:Protein Subunits; D020543:Proteome; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase