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Characterization of a Novel Coronavirus Associated with Severe Acute Respiratory Syndrome
Paul A. Rota,1*M. Steven Oberste,1Stephan S. Monroe,1W. Allan Nix,1Ray Campagnoli,1Joseph P. Icenogle,1Silvia Peñaranda,1Bettina Bankamp,1Kaija Maher,1Min-hsin Chen,1Suxiong Tong,1Azaibi Tamin,1Luis Lowe,1Michael Frace,1Joseph L. DeRisi,2Qi Chen,1David Wang,2Dean D. Erdman,1Teresa C. T. Peret,1Cara Burns,1Thomas G. Ksiazek,1Pierre E. Rollin,1Anthony Sanchez,1Stephanie Liffick,1Brian Holloway,1Josef Limor,1Karen McCaustland,1Melissa Olsen-Rasmussen,1Ron Fouchier,3Stephan Günther,4Albert D. M. E. Osterhaus,3Christian Drosten,4Mark A. Pallansch,1Larry J. Anderson,1William J. Bellini1
In March 2003, a novel coronavirus (SARS-CoV) was discoveredin association with cases of severe acute respiratorysyndrome(SARS). The sequence of the complete genome of SARS-CoV wasdetermined, and the initial characterization of the viral genomeis presented in this report. The genome of SARS-CoV is 29,727nucleotides in length and has 11 open reading frames, and itsgenome organization is similar to that of other coronaviruses.Phylogenetic analyses and sequence comparisons showed that SARS-CoVis not closelyrelated to anyof the previouslycharacterized coronaviruses.
1 National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. 2 Departments of Biochemistry and Biophysics, University of California–San Francisco, San Francisco, CA 94143, USA. 3 Department of Virology, Erasmus University, Rotterdam, 3000 DR, Netherlands. 4 Department of Virology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.
* To whom correspondence should be addressed. E-mail: prota{at}cdc.gov
Several hundred cases of severe atypical pneumonia of unknownetiology were reported in Guangdong Province of the People'sRepublic of China beginning in late 2002. After similar caseswere detected in patients in Hong Kong, Vietnam, and Canadaduring February and March 2003, the World Health Organization(WHO) issued a global alert for the illness, designated "severeacute respiratory syndrome" (SARS). In mid-March 2003, SARSwas recognized in health care workers and household memberswho had cared for patients with severe respiratory illness inHong Kong and Vietnam. Many of these cases could be traced throughmultiple chains of transmission to a health care worker fromGuangdong Province who visited Hong Kong, where he was hospitalizedwith pneumonia and died. By late April 2003, over 4300 SARScases and 250 SARS-related deaths were reported to WHO fromover 25 countries around the world. Most of these cases occurredafter exposure to SARS patients in household or health caresettings. The incubation period for the disease is usually from2 to 7 days. Infection is usually characterized by fever, whichis followed a few days later by a dry nonproductive cough andshortness of breath. Death from progressive respiratory failureoccurs in about 3% to nearly 10% of cases (1–4).
In response to this outbreak, WHO coordinated an internationalcollaboration that included clinical, epidemiologic, and laboratoryinvestigations, and initiated efforts to control the spreadof SARS. Attempts to identify the etiology of the SARS outbreakwere successful during the third week of March 2003, when laboratoriesin the United States, Canada, Germany, and Hong Kong isolateda novel coronavirus (SARS-CoV) from SARS patients. Unlike otherhuman coronaviruses, it was possible to isolate SARS-CoV inVero cells. Evidence of SARS-CoV infection has now been documentedin SARS patients throughout the world. SARS-CoV RNA has frequentlybeen detected in respiratory specimens, and convalescent-phaseserum specimens from SARS patients contain antibodies that reactwith SARS-CoV. There is strong evidence that this new virusis etiologically linked to the outbreak of SARS (5–7).
The coronaviruses (order Nidovirales, family Coronaviridae,genus Coronavirus) are a diverse group of large, enveloped,positive-stranded RNA viruses that cause respiratory and entericdiseases in humans and other animals. At 30,000 nucleotides(nt), their genome is the largest found in any of the RNA viruses.There are three groups of coronaviruses; groups 1 and 2 containmammalian viruses, whereas group 3 contains only avian viruses.Within each group, coronaviruses are classified into distinctspecies by host range, antigenic relationships, and genomicorganization. Coronaviruses typically have narrow host rangesand are fastidious in cell culture. The viruses can cause severedisease in many animals; and several viruses, including infectiousbronchitis virus, feline infectious peritonitis virus, and transmissiblegastroenteritis virus, are important veterinary pathogens. Humancoronaviruses (HCoVs) are found in both group 1 (HCoV-229E)and group 2 (HCoV-OC43) and are responsible for 30% of mildupper respiratory tract illnesses (8–10).
Sequence analysis of a limited region of the replicase (rep)gene suggested that SARS-CoV was distinct from all other coronaviruses(5–7). In this report, we compare the sequence of theentire genome of SARS-CoV (Urbani strain) to the genomic sequencesof other coronaviruses.
Genome organization. The sequence of the entire genome of SARS-CoV(GenBank accession number AY278741
[GenBank]
) was obtained by severalapproaches (11). During completion of this manuscript, otherlaboratories determined the genomic sequences of three additionalstrains of SARS-CoV. These nucleotide sequences vary at only24 positions (table S3).
The genome of SARS-CoV is a 29,727-nucleotide, polyadenylatedRNA, and 41% of the residues are G or C (the range for publishedcomplete coronavirus genome sequences is 37 to 42%). The genomicorganization is typical of coronaviruses, having the characteristicgene order [5'-replicase (rep), spike (S), envelope (E), membrane(M), and nucleocapsid (N)-3'] and short untranslated regionsat both termini (Fig. 1A and table S1). The SARS-CoV rep gene,which comprises approximately two-thirds of the genome, is predictedto encode two polyproteins (encoded by ORF1a and ORF1b) thatundergo cotranslational proteolytic processing. There are fouropen reading frames (ORFs) downstream of rep that are predictedto encode the structural proteins S, E, M, and N, which arecommon to all known coronaviruses. The gene encoding hemagglutinin-esterase,which is present between ORF1b and S in group 2 and some group3 coronaviruses (8), was not found.
Fig. 1. Genome organization and mRNA mapping of SARS-CoV. (A) Overall organization of the 29,727-nt SARS-CoV genomic RNA. The 72-nt leader sequence is represented by a small orange square at the 5' terminus of the genome and the subgenomic mRNAs (below). Predicted ORFs 1a and 1b, encoding the nonstructural polyproteins, and those encoding the S, E, M, and N structural proteins are indicated. The vertical position of the boxes indicates the phase of the reading frame. (B) Expanded view of the structural protein coding region and predicted mRNA transcripts. Known structural protein coding regions (blue boxes) and reading frames X1 to X5, encoding potential nonstructural proteins longer than 50 amino acids (gray boxes), are indicated. Lengths and map locations of the 3'-coterminal mRNAs, as predicted by identification of conserved transcription-regulating sequences, are indicated. (C) Northern blot analysis of SARS-CoV mRNAs. Poly(A)+ RNA was separated on a formaldehyde-agarose gel, transferred to a nylon membrane, and hybridized with a digoxigenin-labeled riboprobe overlapping the 3' untranslated region. Signals were visualized by chemiluminescence. Sizes of the SARS-CoV mRNAs were calculated by interpolation from a log-linear fit of those of the molecular mass marker. Lane 1, SARS-CoV mRNA; lane 2, Vero E6 cell mRNA; lane 3, molecular mass marker (sizes in kilobases).
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Coronaviruses also encode a number of nonstructural proteinsthat are located between S and E, between M and N, or downstreamof N. These nonstructural proteins, which vary widely amongthe different coronavirus species, are of unknown function andare dispensable for virus replication (8). The genome of SARS-CoVcontains ORFs for five potential nonstructural proteins thatare more than 50 amino acids long in these intergenic regions(Fig. 1B, Table 1, and table S1). Two overlapping ORFs encodingpredicted proteins of 274 and 154 amino acids (termed X1 andX2, respectively) are located between S and E. Three additionalpotential nonstructural genes, X3, X4, and X5 (encoding proteinsof 63, 122, and 84 amino acids, respectively), are located betweenM and N. In addition to the five ORFs encoding the predictednonstructural proteins described above, there are also two smallerORFs between M and N, encoding predicted proteins of less than50 amino acids (Table 1). Searches of the GenBank database (withBLAST and FastA) indicated that there is no significant sequencesimilarity between these potential nonstructural proteins ofSARS-CoV and any other proteins (12). Note that there are ORFsencoding predicted proteins more than 50 amino acids long inthe structural genes of SARS-CoV (such as N, S, and rep). Manyshort ORFs are present in the structural genes. They are unlikelyto be expressed and, for simplicity, they are not shown in Fig. 1.
Table 1. Classification of ORFs encoding potential nonstructural proteins of SARS-CoV. [The table shows the differences in nomenclature used to describe ORFs encoding potential nonstructural proteins of SARS-CoV in this report and in the report by Marra et al. (30). These differences are in nomenclature only, and the seven nt sequence differences between these strains do not change the position or number of ORFs (table S2). Because the complete SARS-CoV sequences have been available for only a few weeks and will probably be analyzed in great detail in the upcoming months, any nomenclature proposed at this time should be considered preliminary. The nomenclature used for the nonstructural proteins X1 to X5 is expected to be clarified once experiments on the transcriptional expression of the SARS-CoV genome are reported.]
In Marra et al. (30), all of the ORFs, including those encoding the predicted replicase protein and structural proteins, are numbered sequentially from the 5' terminus of the genome. This table shows only ORFs encoding predicted nonstructural proteins.
The favored model for production of subgenomic mRNAs of coronavirusesproposes that discontinuous transcription occurs during synthesisof the negative strand (13). Subgenomic negative strands containinga complementary copy of the leader sequence at their 3' terminiserve as templates for synthesis of subgenomic mRNAs. In additionto the site at the 5' terminus of the genome, the TRS conservedcore sequence appears six times in the remainder of the genome.The positions of the TRS in the genome of SARS-CoV predict thatsubgenomic mRNAs of 8.3, 4.5, 3.4, 2.5, 2.0, and 1.7 kb, notincluding the poly(A) tail, should be produced (Fig. 1, A and B,and table S1). At least five subgenomic mRNAs were detectedby Northern hybridization of RNA from SARS-CoV–infectedcells, using a probe derived from the 3' untranslated region(Fig. 1C). The calculated sizes of the five predominant bandscorrespond to the sizes of five of the predicted subgenomicmRNAs of SARS-CoV; we cannot exclude the possibility that other,low-abundance mRNAs are present. Full-length genomic RNA wasnot detected, probably because it is the least prevalent viralRNA in infected cells (8). The predicted 2.0-kb transcript wasalso not detected, which suggests that the consensus TRS atnt 27,771 to 27,778 is not used or that it is a low-abundancemRNA. By analogy with other coronaviruses (8), the 8.3-kb and1.7-kb subgenomic mRNAs are predicted to be monocistronic, directingtranslation of S and N, respectively, whereas multiple proteinscould be translated from the 4.5-kb (X1, X2, and E), 3.4-kb(M and X3), and 2.5-kb (X4 and X5) mRNAs. A consensus TRS isnot found directly upstream of the ORF encoding the predictedE protein (14), and a monocistronic mRNA that would be predictedto code for E could not be clearly identified by Northern blotanalysis. It is possible that the 3.4-kb band contained morethan one mRNA species that were not resolved in the gel or thatthe monocistronic mRNA for E is a low-abundance message. Also,in some coronaviruses, the E protein is translated from thesecond ORF on a polycistronic mRNA (15, 16).
Phylogenetic analyses of the sequence of SARS-CoV. To determinethe relationship between SARS-CoV and the previously characterizedcoronaviruses, we compared the predicted amino acid sequencesfor three well-defined enzymatic proteins encoded by the repgene and the four major structural proteins of SARS-CoV withthose from representative viruses for each of the species ofcoronavirus for which complete genomic sequence informationwas available (Fig. 2). The topologies of the resulting phylogramsare remarkably similar (Fig. 2A). For each protein analyzed,the species formed monophyletic clusters consistent with theestablished taxonomic groups. In all cases, SARS-CoV sequencessegregated into a fourth, well-resolved branch. These clusterswere supported by bootstrap values above 90% [1000 replicates(17)]. Consistent with pairwise comparisons between the previouslycharacterized coronavirus species (Fig. 2B), there was greatersequence conservation in the enzymatic proteins [3CLpro, polymerase(POL), and helicase (HEL)] than among the structural proteins(S, E, M, and N). These results indicate that SARS-CoV is notclosely related to any of the previously characterized coronavirusesand forms a distinct group within the genus Coronavirus. SARS-CoVis approximately equidistant from all previously characterizedcoronaviruses, just as the existing groups are from one another.Detailed pairwise comparison by dot-plot analysis identifiedmany regions of amino acid conservation within each protein(fig. S1), but the overall level of similarity between SARS-CoVand the other coronaviruses was low (Fig. 2B). No evidence forrecombination was detected when the predicted protein sequenceswere analyzed with the program Sim-Plot (17, 18).
Fig. 2. Phylogenetic analysis and pairwise identities of coronavirus proteins. Predicted amino acid sequences of SARS-CoV proteins were compared with those from reference viruses representing each species in the three groups of coronaviruses for which complete genomic sequence information was available [group 1(G1): human coronavirus 229E (HCoV-229E), af304460; porcine epidemic diarrhea virus (PEDV), af353511; transmissible gastroenteritis virus (TGEV), aj271965. Group 2 (G2): bovine coronavirus (BCoV), af220295; murine hepatitis virus (MHV), af201929. Group 3 (G3): infectious bronchitis virus (IBV), m95169]. Sequences for representative strains of other coronavirus species, for which partial sequence information was available, were included for some of the structural protein comparisons [group 1: canine coronavirus (CCoV), d13096; feline coronavirus (FCoV), ay204704; porcine respiratory coronavirus (PRCoV), z24675. Group 2: human coronavirus OC43 (HCoV-OC43), m76373, l14643, m93390; porcine hemagglutinating encephalomyelitis virus (HEV), ay078417; rat coronavirus (RtCoV), af207551]. (A) Sequence alignments and neighbor-joining trees were generated by the use of ClustalX 1.83 with the Gonnet protein comparison matrix. The resulting trees were adjusted for final output with treetool 2.0.1. (B) Uncorrected pairwise distances were calculated from the aligned sequences with the Distances program from the Wisconsin Sequence Analysis Package, version 10.2 (Accelrys, Burlington, MA). Distances were converted to percent identity by subtracting from 100. aa, amino acid.
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Predicted replicase gene products of SARS-CoV. Coronavirusesencode a chymotrypsin-like protease, 3CLpro, that is analogousto the main picornaviral protease 3Cpro (19). They also encodeone (group 3) or two (groups 1 and 2) papain-like proteases,termed PLP1pro and PLP2pro, which are analogous to the foot-and-mouthdisease virus leader protease Lpro. Overall, gene products ofORF1a are poorly conserved among different coronaviruses, exceptfor these protease sequences (fig. S1). The predicted gene productof ORF1a of SARS-CoV appears to contain only one PLPpro domainat amino acids 1632 to 1847. The 3CLpro catalytic histidineand cysteine residues are fully conserved among all coronaviruses(SARS-CoV amino acids His3281 and Cys3385), but coronavirusesappear to lack the conserved catalytic acidic residue that ischaracteristic of other 3C-like proteases (19). The coronavirusreplicase polyprotein is synthesized by a –1 ribosomalframeshift at a conserved "slippery" site (UUUAAAC) immediatelyupstream of a pseudoknot structure in the overlap of ORF1a andORF1b. This polyprotein is autocatalytically processed to yieldthe mature viral proteases PLPpro and 3CLpro, the RNA-dependentpolymerase (POL), the RNA helicase (HEL), and other proteinswhose functions have not been well characterized. The predictedribosomal frame shift at the SARS-CoV slippery site (nt 13,392to 13,398) would result in translation of 7073 amino acids froma single start site.
Analysis of the predicted structural proteins of SARS-CoV. Thestructural proteins of coronaviruses (S, E, M, and N) functionduring host cell entry and virion morphogenesis and release(20). During virion assembly, N binds to a defined packagingsignal on viral RNA, leading to the formation of the helicalnucleocapsid. M is localized at specialized intracellular membranestructures, and interactions between the M and E proteins andnucleocapsids result in budding through the membrane. In somegroup 2 coronaviruses, the C terminus of M interacts with thenucleocapsid to form a core structure (21). The S protein isincorporated into the viral envelope, again by interaction withM, and mature virions are released from smooth vesicles (22).Bands corresponding to the predicted N and S proteins of SARS-CoVwere visible in preparations of purified virions that were analyzedby SDS–polyacrylamide gel electrophoresis; however, theassignment of other proteins in virions awaits the availabilityof specific antibodies to identify these viral proteins (fig.S4).
The S proteins of coronaviruses are large type-I membrane glycoproteinsthat are responsible both for binding to receptors on host cellsand for membrane fusion. The S proteins of some coronavirusesare cleaved into S1 and S2 subunits. S proteins also containimportant virus-neutralizing epitopes, and amino acid changesin the S proteins can dramatically affect the virulence andin vitro host cell tropism of the virus (23, 24). Because ofthe low level of similarity (20 to 27% pairwise amino acid identity)between the predicted amino acid sequence of the S protein ofSARS-CoV and the S proteins of other coronaviruses (Fig. 2Band fig. S1A), the comparison of primary amino acid sequencesdoes not provide insight into the receptor-binding specificityor antigenic properties of SARS-CoV.
The S protein of SARS-CoV has 23 potential N-linked glycosylationsites (table S2). Functional motifs at the amino (N) and carboxyl(C) termini of the S protein that are conserved among the coronavirusesare also present in the predicted SARS-CoV S protein, althoughthe S2 domain is more conserved than the S1 domain. The N terminusof the SARS-CoV S protein contains a short type-I signal sequencecomposed of hydrophobic amino acids that are presumably removedduring cotranslational transport through the endoplasmic reticulum.The C terminus, consisting of a transmembrane domain and a cytoplasmictail rich in cysteine residues, is highly conserved in SARS-CoV(Fig. 3). At 52 amino acids in length, the SARS-CoV S proteinis predicted to have the shortest transmembrane domain and cytoplasmictail of any coronavirus analyzed (Fig. 3) (range, 61 to 74 aminoacids).
Fig. 3. Conserved motifs in coronavirus S proteins. Alignment of the C-terminal region of the SARS-CoV and reference coronavirus S proteins was generated with ClustalX 1.83. Residues that match the SARS-CoV sequence exactly are boxed. The membrane-spanning domain and cytoplasmic tails are delineated with arrows. The amino acid sequence Y(V/I)KWPW(Y/W)VWL (26) is a conserved motif in all three coronavirus groups. The cysteine-rich region, which overlaps the membrane-spanning region and the cytoplasmic region, is also found in all coronavirus groups.
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The current paradigm of protein-mediated membrane fusion proposesthe collapse of alpha-amphipathic regions in the C half of thecoronavirus S protein into coiled coils, thus bringing a fusionpeptide toward the transmembrane domain, resulting in cellularand viral membrane fusion. Two or three alpha-amphipathic regionsare predicted for the C half of coronavirus S proteins. An alpha-amphipathicregion of 116 amino acids was predicted with high confidenceat positions 884 to 999 of the SARS-CoV S protein (fig. S2).Syncytia formation, however, is not a prominent feature of SARS-CoVinfection of Vero cells (5). The SARS-CoV S protein lacks thebasic amino acid cleavage site found in group 2 and group 3coronaviruses (25), suggesting that the SARS-CoV S protein isprobably not cleaved into S1 and S2 subunits.
Although overall sequence conservation is low (Fig. 2B), thepredicted E, M, and N proteins of SARS-CoV contain conservedmotifs that are found in other coronaviruses. Consistent withthe E proteins of other coronaviruses, the predicted E proteinof SARS-CoV contains a hydrophobic domain (residues 12 to 37)flanked by charged residues and followed by a cysteine-richregion. The N-terminal domains of coronavirus M proteins areexposed on the viral surface, whereas the C terminus is insidethe viral membrane. Most coronavirus M proteins, including thepredicted M protein of SARS-CoV, contain three hydrophobic transmembranedomains in the N-terminal half of the protein, although someviruses have four. A highly conserved amino acid sequence [SwWSFNPE(26)], immediately following the third hydrophobic domain, isSMWSFNPE in the SARS-CoV M protein. The M proteins of coronavirusesare invariably glycosylated near the N terminus. Group 1 andgroup 3 coronaviruses are N-glycosylated, whereas those of group2 viruses are O-glycosylated (27, 28). The predicted M proteinof SARS-CoV has an NGT near its N terminus, suggesting thatthis protein is N-glycosylated at position 4.
The predicted N protein of SARS-CoV is a highly charged basicprotein of 422 amino acids (range for other coronaviruses, 377to 454) with seven successive hydrophobic residues near themiddle of the protein. Although the overall amino acid sequencehomology among coronavirus N proteins is low (Fig. 2B), a highlyconserved motif [FYYL-GTGP (26)] occurs in the N-terminal halfof all coronavirus N proteins, including that of SARS-CoV. Otherconserved residues occur near this highly conserved motif (fig.S3).
Conclusion. The completion of the genomic sequence of SARS-CoVprovides a first look at the molecular characteristics of thisvirus and clearly demonstrates that this virus has featurestypical of a coronavirus, while it also has features that distinguishit from all previously sequenced coronaviruses. Relative toother coronaviruses, no significant major genomic rearrangementsor any examples of large insertions or deletions in the genescoding for the replicase, S, E, M, or N proteins were found.Like some other coronaviruses, SARS-CoV has several small nonstructuralORFs that are found between the genes for S and E and betweenthe genes for M and N. SARS-CoV is a novel virus that is phylogeneticallydistinct from other characterized coronaviruses. The geneticdistance between SARS-CoV and any other coronavirus in all generegions implies that no large part of the SARS-CoV genome wasderived from other known viruses. The SARS-CoV genomic sequencedoes not provide obvious clues concerning the potential animalorigins of this pathogen.
The genome of SARS-CoV has several unique features that couldbe of biological significance. The short anchor of the S protein,the specific number and location of small ORFs, and the presenceof only one copy of the PLPpro provide a combination of geneticfeatures that readily differentiate this virus from previouslydescribed coronaviruses. Of course, the significance of anyof these features remains to be determined experimentally.
Successful control of the global SARS epidemic will requirethe development of vaccines and antiviral compounds that effectivelyprevent or treat this disease, as well as rapid and sensitivediagnostic tests to monitor its spread. The availability ofcomplete genomic sequences (table S3) (29) of SARS-CoV in justa few weeks after the discovery of the virus should have animmediate impact on disease control efforts by making it possibleto develop improved diagnostic tests, vaccines, and antiviralagents. The sequence information will also make it possibleto identify the origin and natural reservoir of this virus andto contribute to studies of the immune response to this virusand the pathogenesis of SARS-CoV–related disease. Thestage is set for the international scientific community to respondand to rapidly develop the tools to control this emerging infectiousdisease.
8. M. M. C. Lai, K. V. Holmes, in Fields Virology, D. M. Knipe, P. M. Howley, Eds. (Lippincott Williams & Wilkins, New York, ed. 4, 2001), chap. 35.
9. L. Enjuanes et al., in Virus Taxonomy, M. H. V. van Regenmortal et al., Eds. (Academic Press, New York, 2000), pp. 835–849.
10. K. V. Holmes, in Fields Virology, D. M. Knipe, P. M. Howley, Eds. (Lippincott Williams & Wilkins, New York, ed. 4, 2001), chap. 36.
11. Materials and methods are available as supporting material on Science Online.
12. Although the match was not statistically significant, the C half of potential protein X1 contains a region of similarity with calcium-transporting adenosine triphosphatases.
14. The sequence immediately upstream of the ORF coding for the predicted E protein is GTACGAAC and differs from the sequence of the consensus TRS at the first two positions.
25. Cleavage sites in the S proteins of coronaviruses are RRFRR, RRSRR, RRSRR, RSRR, RARS, and RARR (26) in infectious bronchitis virus, bovine coronavirus, human coronavirus OC43, porcine hemagglutinating encephalomyelitis virus, mouse hepatitis virus, and rat coronavirus, respectively.
26. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
28. C. A. M. de Haan, L. Kuo, P. S. Masters, H. Vennema, P. J. M. Rottier, J. Virol.72, 6838 (1998).[Abstract/Free Full Text]
29. As of this writing, complete genomic sequences of three additional SARS-CoV isolates were available at GenBank (Tor-2 strain, Canada, accession no. ay274119; CUHK-W1 isolate, Hong Kong, accession no. ay278554; and HKU-39849 isolate, Hong Kong, accession no. ay278491). A comparison of these sequences to the sequence described in this paper is shown in table S3.
30. M. A. Marra et al., Science300, 1399 (2003); published online 1 May 2003 (10.1126.science.1085953).[Abstract/Free Full Text]
31. The authors thank the WHO SARS Aetiology Laboratory Investigation Group (Bernhard-Nocht Institute, Hamburg, Germany; Erasmus Universiteit, National Influenza Centre, Rotterdam, Netherlands; Federal Microbiology Laboratories for Health Canada, Winnipeg, Canada; Institut für Virologie, Marburg Germany; Frankfurt A. M. University Hospital, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt, Germany; Chinese Center for Disease Control, Beijing, China; Public Health Laboratory Service Central Public Health Laboratory, London; Prince of Wales Hospital, Hong Kong; National Institute of Infectious Disease, Tokyo, Japan; The Chinese University of Hong Kong, Hong Kong; Government Virus Unit, Hong Kong; Queen Mary Hospital, Hong Kong; and Institute Pasteur, Paris, France) for the open collaboration and sharing of information; Centers for Disease Control (CDC) Laboratory Partners Group for support and suggestions; the Coronavirology Partners Group (S. C. Baker, R. Baric, D. A. Brian, D. Cavanagh, M. R. Denison, M. S. Diamond, B. G. Hogue, K. V. Holmes, J. Leibowitz, S. Perlman, L. J. Saif, L. Sturman, and S. R. Weiss) for many helpful reagents, guidance and discussion; B. W. J. Mahy for advice and discussions and for organizing the Laboratory Partners Conferences; S. Emery for technical support; J. Osborne and S. Sammons for help with the figures; and C. Chesley for editorial assistance. M-h.C. is supported by a CDC/Georgia State University interagency agreement.
Received for publication 18 April 2003. Accepted for publication 30 April 2003.
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16, 241-245
|Abstract »|Full Text »|PDF »
Comparative Analysis of Complete Genome Sequences of Three Avian Coronaviruses Reveals a Novel Group 3c Coronavirus.
P. C. Y. Woo, S. K. P. Lau, C. S. F. Lam, K. K. Y. Lai, Y. Huang, P. Lee, G. S. M. Luk, K. C. Dyrting, K.-H. Chan, and K.-Y. Yuen (2009)
J. Virol.
83, 908-917
|Abstract »|Full Text »|PDF »
Searching immunodominant epitopes prior to epidemic: HLA class II-restricted SARS-CoV spike protein epitopes in unexposed individuals.
J. Yang, E. James, M. Roti, L. Huston, J. A. Gebe, and W. W. Kwok (2009)
Int. Immunol.
21, 63-71
|Abstract »|Full Text »|PDF »
Mechanisms of Severe Acute Respiratory Syndrome Pathogenesis and Innate Immunomodulation.
Entry from the Cell Surface of Severe Acute Respiratory Syndrome Coronavirus with Cleaved S Protein as Revealed by Pseudotype Virus Bearing Cleaved S Protein.
R. Watanabe, S. Matsuyama, K. Shirato, M. Maejima, S. Fukushi, S. Morikawa, and F. Taguchi (2008)
J. Virol.
82, 11985-11991
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The M, E, and N Structural Proteins of the Severe Acute Respiratory Syndrome Coronavirus Are Required for Efficient Assembly, Trafficking, and Release of Virus-Like Particles.
Y. L. Siu, K. T. Teoh, J. Lo, C. M. Chan, F. Kien, N. Escriou, S. W. Tsao, J. M. Nicholls, R. Altmeyer, J. S. M. Peiris, et al. (2008)
J. Virol.
82, 11318-11330
|Abstract »|Full Text »|PDF »
Prior Immunization with Severe Acute Respiratory Syndrome (SARS)-Associated Coronavirus (SARS-CoV) Nucleocapsid Protein Causes Severe Pneumonia in Mice Infected with SARS-CoV.
F. Yasui, C. Kai, M. Kitabatake, S. Inoue, M. Yoneda, S. Yokochi, R. Kase, S. Sekiguchi, K. Morita, T. Hishima, et al. (2008)
J. Immunol.
181, 6337-6348
|Abstract »|Full Text »|PDF »
T Cell Responses to Whole SARS Coronavirus in Humans.
C. K.-f. Li, H. Wu, H. Yan, S. Ma, L. Wang, M. Zhang, X. Tang, N. J. Temperton, R. A. Weiss, J. M. Brenchley, et al. (2008)
J. Immunol.
181, 5490-5500
|Abstract »|Full Text »|PDF »
The Transmembrane Domain of the Severe Acute Respiratory Syndrome Coronavirus ORF7b Protein Is Necessary and Sufficient for Its Retention in the Golgi Complex.
S. R. Schaecher, M. S. Diamond, and A. Pekosz (2008)
J. Virol.
82, 9477-9491
|Abstract »|Full Text »|PDF »
Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.
R. H. See, M. Petric, D. J. Lawrence, C. P. Y. Mok, T. Rowe, L. A. Zitzow, K. P. Karunakaran, T. G. Voss, R. C. Brunham, J. Gauldie, et al. (2008)
J. Gen. Virol.
89, 2136-2146
|Abstract »|Full Text »|PDF »
Data-driven exploration of 'spatial pattern-time process-driving forces' associations of SARS epidemic in Beijing, China.
J.-F. Wang, G. Christakos, W.-G. Han, and B. Meng (2008)
J. Public Health Med.
30, 234-244
|Abstract »|Full Text »|PDF »
Pathways of Cross-Species Transmission of Synthetically Reconstructed Zoonotic Severe Acute Respiratory Syndrome Coronavirus.
T. Sheahan, B. Rockx, E. Donaldson, D. Corti, and R. Baric (2008)
J. Virol.
82, 8721-8732
|Abstract »|Full Text »|PDF »
Severe acute respiratory syndrome coronavirus 3a protein activates the mitochondrial death pathway through p38 MAP kinase activation.
K. Padhan, R. Minakshi, M. A. B. Towheed, and S. Jameel (2008)
J. Gen. Virol.
89, 1960-1969
|Abstract »|Full Text »|PDF »
Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2.
J. Netland, D. K. Meyerholz, S. Moore, M. Cassell, and S. Perlman (2008)
J. Virol.
82, 7264-7275
|Abstract »|Full Text »|PDF »
Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections.
Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Hepatitis Virus Infections by More than One Mechanism.
S. Hussain, S. Perlman, and T. M. Gallagher (2008)
J. Virol.
82, 7212-7222
|Abstract »|Full Text »|PDF »
The Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus Inhibits Cell Cytokinesis and Proliferation by Interacting with Translation Elongation Factor 1{alpha}.
B. Zhou, J. Liu, Q. Wang, X. Liu, X. Li, P. Li, Q. Ma, and C. Cao (2008)
J. Virol.
82, 6962-6971
|Abstract »|Full Text »|PDF »
The Nucleocapsid Protein of SARS-CoV Induces Transcription of hfgl2 Prothrombinase Gene Dependent on C/EBP Alpha.
M. Han, W. Yan, Y. Huang, H. Yao, Z. Wang, D. Xi, W. Li, Y. Zhou, J. Hou, X. Luo, et al. (2008)
J. Biochem.
144, 51-62
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Cytokine Responses in Porcine Respiratory Coronavirus-Infected Pigs Treated with Corticosteroids as a Model for Severe Acute Respiratory Syndrome.
X. Zhang, K. Alekseev, K. Jung, A. Vlasova, N. Hadya, and L. J. Saif (2008)
J. Virol.
82, 4420-4428
|Abstract »|Full Text »|PDF »
Without Its N-Finger, the Main Protease of Severe Acute Respiratory Syndrome Coronavirus Can Form a Novel Dimer through Its C-Terminal Domain.
N. Zhong, S. Zhang, P. Zou, J. Chen, X. Kang, Z. Li, C. Liang, C. Jin, and B. Xia (2008)
J. Virol.
82, 4227-4234
|Abstract »|Full Text »|PDF »
The discovery of angiotensin-converting enzyme 2 and its role in acute lung injury in mice.
Residues on the Dimer Interface of SARS Coronavirus 3C-like Protease: Dimer Stability Characterization and Enzyme Catalytic Activity Analysis.
S. Chen, J. Zhang, T. Hu, K. Chen, H. Jiang, and X. Shen (2008)
J. Biochem.
143, 525-536
|Abstract »|Full Text »|PDF »
Mechanisms of Zoonotic Severe Acute Respiratory Syndrome Coronavirus Host Range Expansion in Human Airway Epithelium.
T. Sheahan, B. Rockx, E. Donaldson, A. Sims, R. Pickles, D. Corti, and R. Baric (2008)
J. Virol.
82, 2274-2285
|Abstract »|Full Text »|PDF »
Evidence of the Recombinant Origin of a Bat Severe Acute Respiratory Syndrome (SARS)-Like Coronavirus and Its Implications on the Direct Ancestor of SARS Coronavirus.
C.-C. Hon, T.-Y. Lam, Z.-L. Shi, A. J. Drummond, C.-W. Yip, F. Zeng, P.-Y. Lam, and F. C.-C. Leung (2008)
J. Virol.
82, 1819-1826
|Abstract »|Full Text »|PDF »
Severe Acute Respiratory Syndrome-associated Coronavirus Nucleocapsid Protein Interacts with Smad3 and Modulates Transforming Growth Factor-{beta} Signaling.
X. Zhao, J. M. Nicholls, and Y.-G. Chen (2008)
J. Biol. Chem.
283, 3272-3280
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CoVDB: a comprehensive database for comparative analysis of coronavirus genes and genomes.
Y. Huang, S. K. P. Lau, P. C. Y. Woo, and K.-y. Yuen (2008)
Nucleic Acids Res.
36, D504-D511
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Prevalence of Psychiatric Disorders Among Toronto Hospital Workers One to Two Years After the SARS Outbreak.
W. J. Lancee, R. G. Maunder, D. S. Goldbloom, and Coauthors for the Impact of SARS Study (2008)
Psychiatr Serv
59, 91-95
|Abstract »|Full Text »|PDF »
Heptad Repeat-Derived Peptides Block Protease-Mediated Direct Entry from the Cell Surface of Severe Acute Respiratory Syndrome Coronavirus but Not Entry via the Endosomal Pathway.
M. Ujike, H. Nishikawa, A. Otaka, N. Yamamoto, N. Yamamoto, M. Matsuoka, E. Kodama, N. Fujii, and F. Taguchi (2008)
J. Virol.
82, 588-592
|Abstract »|Full Text »|PDF »
Sensitive and Specific Enzyme-Linked Immunosorbent Assay Using Chemiluminescence for Detection of Severe Acute Respiratory Syndrome Viral Infection.
K. Fujimoto, K.-H. Chan, K. Takeda, K.-F. Lo, R. H. K. Leung, and T. Okamoto (2008)
J. Clin. Microbiol.
46, 302-310
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Altered Pathogenesis of Porcine Respiratory Coronavirus in Pigs due to Immunosuppressive Effects of Dexamethasone: Implications for Corticosteroid Use in Treatment of Severe Acute Respiratory Syndrome Coronavirus.
K. Jung, K. P. Alekseev, X. Zhang, D.-S. Cheon, A. N. Vlasova, and L. J. Saif (2007)
J. Virol.
81, 13681-13693
|Abstract »|Full Text »|PDF »
Regulation of IRF-3-dependent Innate Immunity by the Papain-like Protease Domain of the Severe Acute Respiratory Syndrome Coronavirus.
S. G. Devaraj, N. Wang, Z. Chen, Z. Chen, M. Tseng, N. Barretto, R. Lin, C. J. Peters, C.-T. K. Tseng, S. C. Baker, et al. (2007)
J. Biol. Chem.
282, 32208-32221
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Severe acute respiratory syndrome coronavirus Orf3a protein interacts with caveolin.
K. Padhan, C. Tanwar, A. Hussain, P. Y. Hui, M. Y. Lee, C. Y. Cheung, J. S. M. Peiris, and S. Jameel (2007)
J. Gen. Virol.
88, 3067-3077
|Abstract »|Full Text »|PDF »
Specific Asparagine-Linked Glycosylation Sites Are Critical for DC-SIGN- and L-SIGN-Mediated Severe Acute Respiratory Syndrome Coronavirus Entry.
Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1 and Rational Design of an Attenuated Strain.
M. G. Wathelet, M. Orr, M. B. Frieman, and R. S. Baric (2007)
J. Virol.
81, 11620-11633
|Abstract »|Full Text »|PDF »
Severe Acute Respiratory Syndrome Coronavirus Gene 7 Products Contribute to Virus-Induced Apoptosis.
S. R. Schaecher, E. Touchette, J. Schriewer, R. M. Buller, and A. Pekosz (2007)
J. Virol.
81, 11054-11068
|Abstract »|Full Text »|PDF »
Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging Infection.
V. C. C. Cheng, S. K. P. Lau, P. C. Y. Woo, and K. Y. Yuen (2007)
Clin. Microbiol. Rev.
20, 660-694
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Development of Recombinant Nucleoprotein-Based Diagnostic Systems for Lassa Fever.
M. Saijo, M.-C. Georges-Courbot, P. Marianneau, V. Romanowski, S. Fukushi, T. Mizutani, A.-J. Georges, T. Kurata, I. Kurane, and S. Morikawa (2007)
Clin. Vaccine Immunol.
14, 1182-1189
|Abstract »|Full Text »|PDF »
G1 Phase Cell Cycle Arrest Induced by SARS-CoV 3a Protein via the Cyclin D3/pRb Pathway.
X. Yuan, Z. Yao, J. Wu, Y. Zhou, Y. Shan, B. Dong, Z. Zhao, P. Hua, J. Chen, and Y. Cong (2007)
Am. J. Respir. Cell Mol. Biol.
37, 9-19
|Abstract »|Full Text »|PDF »
Comparison of Immunoglobulin G Responses to the Spike and Nucleocapsid Proteins of Severe Acute Respiratory Syndrome (SARS) Coronavirus in Patients with SARS.
J. Zhao, W. Wang, W. Wang, Z. Zhao, Y. Zhang, P. Lv, F. Ren, and X.-M. Gao (2007)
Clin. Vaccine Immunol.
14, 839-846
|Abstract »|Full Text »|PDF »
SARS molecular epidemiology: a Chinese fairy tale of controlling an emerging zoonotic disease in the genomics era.
One-Year Outcomes and Health Care Utilization in Survivors of Severe Acute Respiratory Syndrome.
C. M. Tansey, M. Louie, M. Loeb, W. L. Gold, M. P. Muller, J. de Jager, J. I. Cameron, G. Tomlinson, T. Mazzulli, S. L. Walmsley, et al. (2007)
Arch Intern Med
167, 1312-1320
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Crystal Structure of a Monomeric Form of Severe Acute Respiratory Syndrome Coronavirus Endonuclease nsp15 Suggests a Role for Hexamerization as an Allosteric Switch.
J. S. Joseph, K. S. Saikatendu, V. Subramanian, B. W. Neuman, M. J. Buchmeier, R. C. Stevens, and P. Kuhn (2007)
J. Virol.
81, 6700-6708
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Viral Proteomics.
K. L. Maxwell and L. Frappier (2007)
Microbiol. Mol. Biol. Rev.
71, 398-411
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Identification and Characterization of Dominant Helper T-Cell Epitopes in the Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus.
J. Zhao, Q. Huang, W. Wang, Y. Zhang, P. Lv, and X.-M. Gao (2007)
J. Virol.
81, 6079-6088
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Severe Acute Respiratory Syndrome Coronavirus Accessory Protein 6 Is a Virion-Associated Protein and Is Released from 6 Protein-Expressing Cells.
Natural Mutations in the Receptor Binding Domain of Spike Glycoprotein Determine the Reactivity of Cross-Neutralization between Palm Civet Coronavirus and Severe Acute Respiratory Syndrome Coronavirus.
L. Liu, Q. Fang, F. Deng, H. Wang, C. E. Yi, L. Ba, W. Yu, R. D. Lin, T. Li, Z. Hu, et al. (2007)
J. Virol.
81, 4694-4700
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Spike protein of SARS-CoV stimulates cyclooxygenase-2 expression via both calcium-dependent and calcium-independent protein kinase C pathways.
M. Liu, Y. Yang, C. Gu, Y. Yue, K. K. Wu, J. Wu, and Y. Zhu (2007)
FASEB J
21, 1586-1596
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Human Coronavirus 229E Papain-Like Proteases Have Overlapping Specificities but Distinct Functions in Viral Replication.
J. Ziebuhr, B. Schelle, N. Karl, E. Minskaia, S. Bayer, S. G. Siddell, A. E. Gorbalenya, and V. Thiel (2007)
J. Virol.
81, 3922-3932
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The Cytoplasmic Tail of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Contains a Novel Endoplasmic Reticulum Retrieval Signal That Binds COPI and Promotes Interaction with Membrane Protein.
A Severe Acute Respiratory Syndrome Coronavirus That Lacks the E Gene Is Attenuated In Vitro and In Vivo.
M. L. DeDiego, E. Alvarez, F. Almazan, M. T. Rejas, E. Lamirande, A. Roberts, W.-J. Shieh, S. R. Zaki, K. Subbarao, and L. Enjuanes (2007)
J. Virol.
81, 1701-1713
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Comparative Analysis of Twelve Genomes of Three Novel Group 2c and Group 2d Coronaviruses Reveals Unique Group and Subgroup Features.
P. C. Y. Woo, M. Wang, S. K. P. Lau, H. Xu, R. W. S. Poon, R. Guo, B. H. L. Wong, K. Gao, H.-w. Tsoi, Y. Huang, et al. (2007)
J. Virol.
81, 1574-1585
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Recombinant Truncated Nucleocapsid Protein as Antigen in a Novel Immunoglobulin M Capture Enzyme-Linked Immunosorbent Assay for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus Infection.
F. Yu, M. Q. Le, S. Inoue, F. Hasebe, M. d. C. Parquet, S. Morikawa, and K. Morita (2007)
Clin. Vaccine Immunol.
14, 146-149
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The ORF7b Protein of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Is Expressed in Virus-Infected Cells and Incorporated into SARS-CoV Particles.
S. R. Schaecher, J. M. Mackenzie, and A. Pekosz (2007)
J. Virol.
81, 718-731
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Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus.
P. B. McCray Jr., L. Pewe, C. Wohlford-Lenane, M. Hickey, L. Manzel, L. Shi, J. Netland, H. P. Jia, C. Halabi, C. D. Sigmund, et al. (2007)
J. Virol.
81, 813-821
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Clinical Disease in Children Associated With Newly Described Coronavirus Subtypes.
J. Kuypers, E. T. Martin, J. Heugel, N. Wright, R. Morrow, and J. A. Englund (2007)
Pediatrics
119, e70-e76
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Full-length genome sequences of two SARS-like coronaviruses in horseshoe bats and genetic variation analysis..
W. Ren, W. Li, M. Yu, P. Hao, Y. Zhang, P. Zhou, S. Zhang, G. Zhao, Y. Zhong, S. Wang, et al. (2006)
J. Gen. Virol.
87, 3355-3359
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Identifying Epitopes Responsible for Neutralizing Antibody and DC-SIGN Binding on the Spike Glycoprotein of the Severe Acute Respiratory Syndrome Coronavirus..
Y.-P. Shih, C.-Y. Chen, S.-J. Liu, K.-H. Chen, Y.-M. Lee, Y.-C. Chao, and Y.-M. A. Chen (2006)
J. Virol.
80, 10315-10324
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Putative cis-Acting Stem-Loops in the 5' Untranslated Region of the Severe Acute Respiratory Syndrome Coronavirus Can Substitute for Their Mouse Hepatitis Virus Counterparts.
H. Kang, M. Feng, M. E. Schroeder, D. P. Giedroc, and J. L. Leibowitz (2006)
J. Virol.
80, 10600-10614
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Construction of a Severe Acute Respiratory Syndrome Coronavirus Infectious cDNA Clone and a Replicon To Study Coronavirus RNA Synthesis.
F. Almazan, M. L. DeDiego, C. Galan, D. Escors, E. Alvarez, J. Ortego, I. Sola, S. Zuniga, S. Alonso, J. L. Moreno, et al. (2006)
J. Virol.
80, 10900-10906
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Extremely Low Exposure of a Community to Severe Acute Respiratory Syndrome Coronavirus: False Seropositivity due to Use of Bacterially Derived Antigens..
D. T. M. Leung, W. W. C. van Maren, F. K. L. Chan, W. S. Chan, A. W. I. Lo, C. H. Ma, F. C. H. Tam, K. F. To, P. K. S. Chan, J. J. Y. Sung, et al. (2006)
J. Virol.
80, 8920-8928
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Accumulation of Recombinant SARS-CoV Spike Protein in Plant Cytosol and Chloroplasts Indicate Potential for Development of Plant-Derived Oral Vaccines.
H.-Y. Li, S. Ramalingam, and M.-L. Chye (2006)
Experimental Biology and Medicine
231, 1346-1352
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Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: Engineering a recombination-resistant genome.
B. Yount, R. S. Roberts, L. Lindesmith, and R. S. Baric (2006)
PNAS
103, 12546-12551
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Crystal structure and mechanistic determinants of SARS coronavirus nonstructural protein 15 define an endoribonuclease family.
S. Ricagno, M.-P. Egloff, R. Ulferts, B. Coutard, D. Nurizzo, V. Campanacci, C. Cambillau, J. Ziebuhr, and B. Canard (2006)
PNAS
103, 11892-11897
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Severe acute respiratory syndrome coronavirus 7a accessory protein is a viral structural protein..
C. Huang, N. Ito, C.-T. K. Tseng, and S. Makino (2006)
J. Virol.
80, 7287-7294
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Crystal structure of nonstructural protein 10 from the severe acute respiratory syndrome coronavirus reveals a novel fold with two zinc-binding motifs..
J. S. Joseph, K. S. Saikatendu, V. Subramanian, B. W. Neuman, A. Brooun, M. Griffith, K. Moy, M. K. Yadav, J. Velasquez, M. J. Buchmeier, et al. (2006)
J. Virol.
80, 7894-7901
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Conformational States of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Ectodomain.
F. Li, M. Berardi, W. Li, M. Farzan, P. R. Dormitzer, and S. C. Harrison (2006)
J. Virol.
80, 6794-6800
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Comparative Analysis of 22 Coronavirus HKU1 Genomes Reveals a Novel Genotype and Evidence of Natural Recombination in Coronavirus HKU1.
P. C. Y. Woo, S. K. P. Lau, C. C. Y. Yip, Y. Huang, H.-W. Tsoi, K.-H. Chan, and K.-Y. Yuen (2006)
J. Virol.
80, 7136-7145
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Bats: Important Reservoir Hosts of Emerging Viruses.
C. H. Calisher, J. E. Childs, H. E. Field, K. V. Holmes, and T. Schountz (2006)
Clin. Microbiol. Rev.
19, 531-545
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Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro.
T.-Y. Ling, M.-D. Kuo, C.-L. Li, A. L. Yu, Y.-H. Huang, T.-J. Wu, Y.-C. Lin, S.-H. Chen, and J. Yu (2006)
PNAS
103, 9530-9535
|Abstract »|Full Text »|PDF »
Coronavirus HKU1 and Other Coronavirus Infections in Hong Kong..
S. K. P. Lau, P. C. Y. Woo, C. C. Y. Yip, H. Tse, H.-w. Tsoi, V. C. C. Cheng, P. Lee, B. S. F. Tang, C. H. Y. Cheung, R. A. Lee, et al. (2006)
J. Clin. Microbiol.
44, 2063-2071
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Antigenic and Immunogenic Characterization of Recombinant Baculovirus-Expressed Severe Acute Respiratory Syndrome Coronavirus Spike Protein: Implication for Vaccine Design..
Y. He, J. Li, S. Heck, S. Lustigman, and S. Jiang (2006)
J. Virol.
80, 5757-5767
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Ultrastructure and Origin of Membrane Vesicles Associated with the Severe Acute Respiratory Syndrome Coronavirus Replication Complex..
E. J. Snijder, Y. van der Meer, J. Zevenhoven-Dobbe, J. J. M. Onderwater, J. van der Meulen, H. K. Koerten, and A. M. Mommaas (2006)
J. Virol.
80, 5927-5940
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Cross-Neutralization of Human and Palm Civet Severe Acute Respiratory Syndrome Coronaviruses by Antibodies Targeting the Receptor-Binding Domain of Spike Protein.
Y. He, J. Li, W. Li, S. Lustigman, M. Farzan, and S. Jiang (2006)
J. Immunol.
176, 6085-6092
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Specific epitopes of the structural and hypothetical proteins elicit variable humoral responses in SARS patients.
S C S Chow, C Y S Ho, T T Y Tam, C Wu, T Cheung, P K S Chan, M H L Ng, P K Hui, H K Ng, D M Y Au, et al. (2006)
J. Clin. Pathol.
59, 468-476
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Solution Structure of the Severe Acute Respiratory Syndrome-Coronavirus Heptad Repeat 2 Domain in the Prefusion State.
S. Hakansson-McReynolds, S. Jiang, L. Rong, and M. Caffrey (2006)
J. Biol. Chem.
281, 11965-11971
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Severe acute respiratory syndrome coronavirus papain-like protease: Structure of a viral deubiquitinating enzyme.
K. Ratia, K. S. Saikatendu, B. D. Santarsiero, N. Barretto, S. C. Baker, R. C. Stevens, and A. D. Mesecar (2006)
PNAS
103, 5717-5722
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Functional characterization of heptad repeat 1 and 2 mutants of the spike protein of severe acute respiratory syndrome coronavirus..
W.-E. Chan, C.-K. Chuang, S.-H. Yeh, M.-S. Chang, and S. S.-L. Chen (2006)
J. Virol.
80, 3225-3237
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Mucosal Immunization with Surface-Displayed Severe Acute Respiratory Syndrome Coronavirus Spike Protein on Lactobacillus casei Induces Neutralizing Antibodies in Mice..
J.-S. Lee, H. Poo, D. P. Han, S.-P. Hong, K. Kim, M. W. Cho, E. Kim, M.-H. Sung, and C.-J. Kim (2006)
J. Virol.
80, 4079-4087
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From the Cover: Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation.
M. Anishchenko, R. A. Bowen, S. Paessler, L. Austgen, I. P. Greene, and S. C. Weaver (2006)
PNAS
103, 4994-4999
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Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus..
R. H. See, A. N. Zakhartchouk, M. Petric, D. J. Lawrence, C. P. Y. Mok, R. J. Hogan, T. Rowe, L. A. Zitzow, K. P. Karunakaran, M. M. Hitt, et al. (2006)
J. Gen. Virol.
87, 641-650
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False-Positive Results in a Recombinant Severe Acute Respiratory Syndrome-Associated Coronavirus (SARS-CoV) Nucleocapsid-Based Western Blot Assay Were Rectified by the Use of Two Subunits (S1 and S2) of Spike for Detection of Antibody to SARS-CoV..
M. Maache, F. Komurian-Pradel, A. Rajoharison, M. Perret, J.-L. Berland, S. Pouzol, A. Bagnaud, B. Duverger, J. Xu, A. Osuna, et al. (2006)
Clin. Vaccine Immunol.
13, 409-414
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Glycosylation of the Severe Acute Respiratory Syndrome Coronavirus Triple-Spanning Membrane Proteins 3a and M.
M. Oostra, C. A. M. de Haan, R. J. de Groot, and P. J. M. Rottier (2006)
J. Virol.
80, 2326-2336
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Pyridine N-oxide derivatives are inhibitory to the human SARS and feline infectious peritonitis coronavirus in cell culture.
J. Balzarini, E. Keyaerts, L. Vijgen, F. Vandermeer, M. Stevens, E. De Clercq, H. Egberink, and M. Van Ranst (2006)
J. Antimicrob. Chemother.
57, 472-481
|Abstract »|Full Text »|PDF »
Serum Proteomic Fingerprints of Adult Patients with Severe Acute Respiratory Syndrome.
R. T.K. Pang, T. C.W. Poon, K.C. A. Chan, N. L.S. Lee, R. W.K. Chiu, Y.-K. Tong, R. M.Y. Wong, S. S.C. Chim, S. M. Ngai, J. J.Y. Sung, et al. (2006)
Clin. Chem.
52, 421-429
|Abstract »|Full Text »|PDF »
Cardiovascular complications of severe acute respiratory syndrome.
C-M Yu, R S-M Wong, E B Wu, S-L Kong, J Wong, G W-K Yip, Y O Y Soo, M L S Chiu, Y-S Chan, D Hui, et al. (2006)
Postgrad. Med. J.
82, 140-144
|Abstract »|Full Text »|PDF »
7a Protein of Severe Acute Respiratory Syndrome Coronavirus Inhibits Cellular Protein Synthesis and Activates p38 Mitogen-Activated Protein Kinase.
S. A. Kopecky-Bromberg, L. Martinez-Sobrido, and P. Palese (2006)
J. Virol.
80, 785-793
|Abstract »|Full Text »|PDF »
Evaluation of Affymetrix Severe Acute Respiratory Syndrome Resequencing GeneChips in Characterization of the Genomes of Two Strains of Coronavirus Infecting Humans.
I. M. Sulaiman, X. Liu, M. Frace, N. Sulaiman, M. Olsen-Rasmussen, E. Neuhaus, P. A. Rota, and R. M. Wohlhueter (2006)
Appl. Envir. Microbiol.
72, 207-211
|Abstract »|Full Text »|PDF »
Severe Acute Respiratory Syndrome Coronavirus 3a Protein Is Released in Membranous Structures from 3a Protein-Expressing Cells and Infected Cells.
C. Huang, K. Narayanan, N. Ito, C. J. Peters, and S. Makino (2006)
J. Virol.
80, 210-217
|Abstract »|Full Text »|PDF »
Colonization of Severe Acute Respiratory Syndrome-Associated Coronavirus Among Health-Care Workers Screened by Nasopharyngeal Swab.
H.-T. Ho, M.-S. Chang, T.-Y. Wei, W.-S. Hsieh, C.-C. Hung, H.-M. Yang, and Y.-T. Lu (2006)
Chest
129, 95-101
|Abstract »|Full Text »|PDF »
30,000 nucleotides (nt), their genome is the largest found in any of the RNA viruses. There are three groups of coronaviruses; groups 1 and 2 contain mammalian viruses, whereas group 3 contains only avian viruses. Within each group, coronaviruses are classified into distinct species by host range, antigenic relationships, and genomic organization. Coronaviruses typically have narrow host ranges and are fastidious in cell culture. The viruses can cause severe disease in many animals; and several viruses, including infectious bronchitis virus, feline infectious peritonitis virus, and transmissible gastroenteritis virus, are important veterinary pathogens. Human coronaviruses (HCoVs) are found in both group 1 (HCoV-229E) and group 2 (HCoV-OC43) and are responsible for 
