Relationship of SARS-CoV to other pathogenic RNA viruses explored by tetranucleotide usage profiling.
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BACKGROUND: The exact origin of the cause of the Severe Acute Respiratory Syndrome (SARS) is still an open question. The genomic sequence relationship of SARS-CoV with 30 different single-stranded RNA (ssRNA) viruses of various families was studied using two non-standard approaches. Both approaches began with the vectorial profiling of the tetra-nucleotide usage pattern V for each virus. In approach one, a distance measure of a vector V, based on correlation coefficient was devised to construct a relationship tree by the neighbor-joining algorithm. In approach two, a multivariate factor analysis was performed to derive the embedded tetra-nucleotide usage patterns. These patterns were subsequently used to classify the selected viruses. RESULTS: Both approaches yielded relationship outcomes that are consistent with the known virus classification. They also indicated that the genome of RNA viruses from the same family conform to a specific pattern of word usage. Based on the correlation of the overall tetra-nucleotide usage patterns, the Transmissible Gastroenteritis Virus (TGV) and the Feline CoronaVirus (FCoV) are closest to SARS-CoV. Surprisingly also, the RNA viruses that do not go through a DNA stage displayed a remarkable discrimination against the CpG and UpA di-nucleotide (z = -77.31, -52.48 respectively) and selection for UpG and CpA (z = 65.79,49.99 respectively). Potential factors influencing these biases are discussed. CONCLUSION: The study of genomic word usage is a powerful method to classify RNA viruses. The congruence of the relationship outcomes with the known classification indicates that there exist phylogenetic signals in the tetra-nucleotide usage patterns, that is most prominent in the replicase open reading frames. (+info)
Microbiologic characteristics, serologic responses, and clinical manifestations in severe acute respiratory syndrome, Taiwan.
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The genome of one Taiwanese severe acute respiratory syndrome-associated coronavirus (SARS-CoV) strain (TW1) was 29,729 nt in length. Viral RNA may persist for some time in patients who seroconvert, and some patients may lack an antibody response (immunoglobulin G) to SARS-CoV <21 days after illness onset. An upsurge of antibody response was associated with the aggravation of respiratory failure. (+info)
Severe acute respiratory syndrome-associated coronavirus genotype and its characterization.
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OBJECTIVE: To study the severe acute respiratory syndrome (SARS)-associated coronavirus genotype and its characteristics. METHODS: A SARS-associated coronavirus isolate named ZJ01 was obtained from throat swab samples taken from a patient in Hangzhou, Zhejing province. The complete genome sequence of ZJ01 consisted of 29,715 bp (GenBank accession: AY297028, version: gi: 30910859). Seventeen SARS-associated coronavirus genome sequences in GenBank were compared to analyze the common sequence variations and the probability of co-occurrence of multiple polymorphisms or mutations. Phylogenetic analysis of those sequences was done. RESULTS: By bioinformatics processing and analysis, the 5 loci nucleotides at ZJ01 genome were found being T, T, G, T and T, respectively. Compared with other SARS-associated coronavirus genomes in the GenBank database, an A/G mutation was detected besides the other 4 mutation loci (C:G:C:C/T:T:T:T) involved in this genetic signature. Therefore a new definition was put forward according to the 5 mutation loci. SARS-associated coronavirus strains would be grouped into two genotypes (C:G:A:C:C/T:T:G:T:T), and abbreviated as SARS coronavirus C genotype and T genotype. On the basis of this new definition, the ZJ01 isolate belongs to SARS-associated coronavirus T genotype, first discovered and reported in mainland China. Phylogenetic analysis of the spike protein gene fragments of these SARS-associated coronavirus strains showed that the GZ01 isolate was phylogenetically distinct from other isolates, and compared with groups F1 and F2 of the T genotype, the isolates of BJ01 and CUHK-W1 were more closely related to the GZ01 isolate. It was interesting to find that two (A/G and C/T) of the five mutation loci occurred in the spike protein gene, which caused changes of Asp to Gly and Thr to Ile in the protein, respectively. CONCLUSION: Attention should be paid to whether these genotype and mutation patterns are related to the virus's biological activities,epidemic characteristics and host clinical symptoms. (+info)
Putative caveolin-binding sites in SARS-CoV proteins.
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AIM: To obtain the information of protein-protein interaction between the SARS-CoV proteins and caveolin-1, identify the possible caveolin-binding sites in SARS-CoV proteins. METHODS: On the basis of three related caveolin-binding motifs, amino acid motif search was employed to predict the possible caveolin-1 related interaction domains in the SARS-CoV proteins. The molecular modeling and docking simulation methods were used to confirm the interaction between caveolin-1 and SARS-CoV proteins. RESULTS: Thirty six caveolin-binding motifs in the SARS-CoV proteins have been mapped out using bioinformatics analysis tools. Molecular modeling and simulation have confirmed 8 caveolin-binding sites. These caveolin-binding sites located in replicase 1AB, spike protein, orf3 protein, and M protein, respectively. CONCLUSION: Caveolin-1 may serve as a possible receptor of the SARS-CoV proteins, which may be associated with the SARS-CoV infection, replication, assembly, and budding. (+info)
Evaluation of reverse transcription-PCR assays for rapid diagnosis of severe acute respiratory syndrome associated with a novel coronavirus.
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The reverse transcription (RT)-PCR protocols of two World Health Organization (WHO) severe acute respiratory syndrome (SARS) network laboratories (WHO SARS network laboratories at The University of Hong Kong [WHO-HKU] and at the Bernhard-Nocht Institute in Hamburg, Germany [WHO-Hamburg]) were evaluated for rapid diagnosis of a novel coronavirus (CoV) associated with SARS in Hong Kong. A total of 303 clinical specimens were collected from 163 patients suspected to have SARS. The end point of both WHO-HKU and WHO-Hamburg RT-PCR assays was determined to be 0.1 50% tissue culture infective dose. Using seroconversion to CoV as the "gold standard" for SARS CoV diagnosis, WHO-HKU and WHO-Hamburg RT-PCR assays exhibited diagnostic sensitivities of 61 and 68% (nasopharyngeal aspirate specimens), 65 and 72% (throat swab specimens), 50 and 54% (urine specimens), and 58 and 63% (stool specimens), respectively, with an overall specificity of 100%. For patients confirmed to have SARS CoV and from whom two or more respiratory specimens were collected, testing the second specimen increased the sensitivity from 64 and 71% to 75 and 79% for the WHO-HKU and WHO-Hamburg RT-PCR assays, respectively. Testing more than one respiratory specimen will maximize the sensitivity of PCR assays for SARS CoV. (+info)
Prevalence of IgG antibody to SARS-associated coronavirus in animal traders--Guangdong Province, China, 2003.
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Severe acute respiratory syndrome (SARS) was identified in 2003 as an infectious disease caused by the SARS-associated coronavirus (SARS-CoV), a member of the coronavirus family not observed previously in humans. Because its sequence data differ from that of known human coronaviruses, SARS-CoV is suspected to have crossed the species barrier between an animal host and humans. The SARS outbreak began in China's Guangdong Province, where approximately 1,500 probable cases were identified during November 2002-June 2003. Detection of SARS-like coronavirus has been reported previously in masked palm civets (sometimes called civet cats) and a raccoon dog for sale in a live animal market in Shenzhen municipality. This report summarizes results of an investigation conducted by public health authorities in Guangdong Province, which compared the seroprevalence of SARS-CoV IgG antibody in animal traders (i.e., workers in live animal markets) with that of persons in control groups. The results indicated that 13% of the animal traders, none of whom had SARS diagnosed, had IgG antibody to SARS-CoV, compared with 1%-3% of persons in three control groups. Although the results provide indirect support for the hypothesis of an animal origin for SARS, they also underscore the need for detailed patient histories and more focused animal studies to confirm an animal origin for SARS. (+info)
Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus.
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A previously undescribed coronavirus (CoV) is the etiologic agent responsible for severe acute respiratory syndrome (SARS). Using a panel of contiguous cDNAs that span the entire genome, we have assembled a full-length cDNA of the SARS-CoV Urbani strain, and have rescued molecularly cloned SARS viruses (infectious clone SARS-CoV) that contained the expected marker mutations inserted into the component clones. Recombinant viruses replicated as efficiently as WT virus and both were inhibited by treatment with the cysteine proteinase inhibitor (2S,3S)-transepoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester. In addition, subgenomic transcripts were initiated from the consensus sequence ACGAAC in both the WT and infectious clone SARS-CoV. Availability of a SARS-CoV full-length cDNA provides a template for manipulation of the viral genome, allowing for the rapid and rational development and testing of candidate vaccines and therapeutics against this important human pathogen. (+info)
Prediction of proteinase cleavage sites in polyproteins of coronaviruses and its applications in analyzing SARS-CoV genomes.
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Recently, we have developed a coronavirus-specific gene-finding system, ZCURVE_CoV 1.0. In this paper, the system is further improved by taking the prediction of cleavage sites of viral proteinases in polyproteins into account. The cleavage sites of the 3C-like proteinase and papain-like proteinase are highly conserved. Based on the method of traditional positional weight matrix trained by the peptides around cleavage sites, the present method also sufficiently considers the length conservation of non-structural proteins cleaved by the 3C-like proteinase and papain-like proteinase to reduce the false positive prediction rate. The improved system, ZCURVE_CoV 2.0, has been run for each of the 24 completely sequenced coronavirus genomes in GenBank. Consequently, all the non-structural proteins in the 24 genomes are accurately predicted. Compared with known annotations, the performance of the present method is satisfactory. The software ZCURVE_CoV 2.0 is freely available at http://tubic.tju.edu.cn/sars/. (+info)