About: Mutational dynamics of the SARS coronavirus in cell culture and human populations isolated in 2003

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Mutational dynamics of the SARS coronavirus in cell culture and human populations isolated in 2003
Creator	Ruan, Yijun Zhang, Tao Liu, Jianjun Su, Yun Liu, Edison Lee, Wah Ling, Ai Ooi, Eng Kolatkar, Prasanna Lin, Chia Long, Philip Se-Thoe, Stanton, Lawrence Tang, Kin Vega, Vinsensius
Source	Medline; PMC
abstract	BACKGROUND: The SARS coronavirus is the etiologic agent for the epidemic of the Severe Acute Respiratory Syndrome. The recent emergence of this new pathogen, the careful tracing of its transmission patterns, and the ability to propagate in culture allows the exploration of the mutational dynamics of the SARS-CoV in human populations. METHODS: We sequenced complete SARS-CoV genomes taken from primary human tissues (SIN3408, SIN3725V, SIN3765V), cultured isolates (SIN848, SIN846, SIN842, SIN845, SIN847, SIN849, SIN850, SIN852, SIN3408L), and five consecutive Vero cell passages (SIN2774_P1, SIN2774_P2, SIN2774_P3, SIN2774_P4, SIN2774_P5) arising from SIN2774 isolate. These represented individual patient samples, serial in vitro passages in cell culture, and paired human and cell culture isolates. Employing a refined mutation filtering scheme and constant mutation rate model, the mutation rates were estimated and the possible date of emergence was calculated. Phylogenetic analysis was used to uncover molecular relationships between the isolates. RESULTS: Close examination of whole genome sequence of 54 SARS-CoV isolates identified before 14(th )October 2003, including 22 from patients in Singapore, revealed the mutations engendered during human-to-Vero and Vero-to-human transmission as well as in multiple Vero cell passages in order to refine our analysis of human-to-human transmission. Though co-infection by different quasipecies in individual tissue samples is observed, the in vitro mutation rate of the SARS-CoV in Vero cell passage is negligible. The in vivo mutation rate, however, is consistent with estimates of other RNA viruses at approximately 5.7 × 10(-6 )nucleotide substitutions per site per day (0.17 mutations per genome per day), or two mutations per human passage (adjusted R-square = 0.4014). Using the immediate Hotel M contact isolates as roots, we observed that the SARS epidemic has generated four major genetic groups that are geographically associated: two Singapore isolates, one Taiwan isolate, and one North China isolate which appears most closely related to the putative SARS-CoV isolated from a palm civet. Non-synonymous mutations are centered in non-essential ORFs especially in structural and antigenic genes such as the S and M proteins, but these mutations did not distinguish the geographical groupings. However, no non-synonymous mutations were found in the 3CLpro and the polymerase genes. CONCLUSIONS: Our results show that the SARS-CoV is well adapted to growth in culture and did not appear to undergo specific selection in human populations. We further assessed that the putative origin of the SARS epidemic was in late October 2002 which is consistent with a recent estimate using cases from China. The greater sequence divergence in the structural and antigenic proteins and consistent deletions in the 3' – most portion of the viral genome suggest that certain selection pressures are interacting with the functional nature of these validated and putative ORFs.
has issue date	2004-09-06(xsd:dateTime)
bibo:doi	10.1186/1471-2334-4-32
bibo:pmid	15347429
has license	cc-by
sha1sum (hex)	def1cf77e1ef84f4373a342e23145be05ec5e226
schema:url	https://doi.org/10.1186/1471-2334-4-32
resource representing a document's title	Mutational dynamics of the SARS coronavirus in cell culture and human populations isolated in 2003
has PubMed Central identifier	PMC517714
has PubMed identifier	15347429
schema:publication	BMC Infect Dis
resource representing a document's body	covid:def1cf77e1ef84f4373a342e23145be05ec5e226#body_text
is schema:about of	named entity 'tracing' named entity 'emergence' named entity 'SEVERE ACUTE RESPIRATORY SYNDROME' named entity 'ALLOWS' named entity 'NEW' named entity 'SARS CORONAVIRUS' named entity 'RECENT' named entity 'PATTERNS' named entity 'TRANSMISSION' named entity 'CULTURE' named entity 'ISOLATED' named entity 'CELL CULTURE' named entity 'PATHOGEN' named entity 'ETIOLOGIC AGENT' named entity 'DYNAMICS' named entity 'HUMAN' named entity 'INFECTIOUS DISEASES' named entity 'BMC' named entity 'SARS CORONAVIRUS' named entity 'DYNAMICS' named entity 'ITS' named entity 'HUMAN' named entity 'POPULATIONS' named entity 'EMERGENCE' named entity 'POPULATIONS' named entity 'EXPLORATION' named entity 'EPIDEMIC' named entity 'ability' named entity 'pathogen' named entity 'SARS-CoV' named entity 'haplotypes' named entity 'SARS-CoV' named entity 'Singapore' named entity 'Hong Kong' named entity 'human tissue' named entity 'virus' named entity 'Maximum Likelihood criterion' named entity 'inoculated' named entity 'RNA' named entity 'mutation rate' named entity 'SARS-CoV' named entity 'SARS-CoV' named entity 'genomes' named entity 'virulence' named entity 'viral RNA' named entity 'mutation rate' named entity 'genome' named entity 'SARS-CoV' named entity 'Taiwan' named entity 'quasispecies' named entity 'cell culture' named entity 'goodness-of-fit' named entity 'genome' named entity 'SARS-CoV' named entity 'civet cat' named entity 'Taiwan' named entity 'nucleotides' named entity 'sequence divergence' named entity 'molecular sequence' named entity 'mutation rate' named entity 'rate of mutation' named entity 'SARS-CoV' named entity 'mutation' named entity 'mutation' named entity 'mutation rate' named entity 'mutation rate' named entity 'CLUSTALW'

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