Tracing SARS-coronavirus variant with large genomic deletion.
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ABSTRACT:
SUBMITTER: Chiu RW
PROVIDER: S-EPMC3294368 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesInvestigation whether in depth characterization of virus variant patterns can be used for epidemiological analysis of the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection clusters in Hamburg, Germany.MethodsMetagenomic RNA-sequencing and amplicon-sequencing and subsequent variant calling in 25 respiratory samples from SARS-CoV-2 infected patients involved in the earliest infection clusters in Hamburg.ResultsAmplikon sequencing and cluster analyses of these SARS-CoV-2 sequences allowed the identification of the first infection cluster and five non-related infection clusters occurring at the beginning of the viral entry of SARS-CoV-2 in the Hamburg metropolitan region. Viral genomics together with epidemiological analyses revealed that the index patient acquired the infection in northern Italy and transmitted it to two out of 134 contacts. Single nucleotide polymorphisms clearly distinguished the virus variants of the index and other clusters and allowed us to track in which sequences worldwide these mutations were first described. Minor variant analyses identified the transmission of intra-host variants in the index cluster and household clusters.ConclusionsSARS-CoV-2 variant tracing allows the identification of infection clusters and the follow up of infection chains occurring in the population. Furthermore, the follow up of minor viral variants in infection clusters can provide further resolution on transmission events indistinguishable at a consensus sequence level.
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Project description:The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is reported to have deletions of various sizes. Recently, the large 386-nucleotide deletion (L386del) comprising nucleotide positions 27719-28104 and spanning open reading frames 9-11 has been reported in the genomes of some human isolates from Hong Kong. In this study, archived specimens from 71 patients with SARS who were admitted to the New Territory East Cluster Hospitals in Hong Kong were analyzed to determine whether the L386del variant of SARS-CoV was present. There was no clear relationship between the presence of the L386del variant and SARS clinical severity as defined either by the need for intensive-care therapy and/or ventilation or by death. One patient had evidence of both the L386del variant and the wild-type variant in the same clinical specimen, supporting the idea that SARS-CoV exists as a quasispecies in some patients, although the clinical significance of these quasispecies remains unclear.
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Project description:Set of microarray experiments used to identify an unknown coronavirus in a viral culture derived from a patient with SARS. March 2003. Keywords = SARS Keywords = coronavirus Keywords = viral discovery Keywords = viruses Keywords = respiratory infection
2010-06-05 | E-GEOD-546 | biostudies-arrayexpress
Project description:The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-β levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-β responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.
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Project description:Set of microarray experiments used to identify an unknown coronavirus in a viral culture derived from a patient with SARS. March 2003. Keywords = SARS Keywords = coronavirus Keywords = viral discovery Keywords = viruses Keywords = respiratory infection Keywords: repeat sample
2003-10-19 | GSE546 | GEO
Project description:SARS-CoV-2 is a new human coronavirus (CoV), which emerged in China in late 2019 and is responsible for the global COVID-19 pandemic that caused more than 97 million infections and 2 million deaths in 12 months. Understanding the origin of this virus is an important issue, and it is necessary to determine the mechanisms of viral dissemination in order to contain future epidemics. Based on phylogenetic inferences, sequence analysis and structure-function relationships of coronavirus proteins, informed by the knowledge currently available on the virus, we discuss the different scenarios on the origin-natural or synthetic-of the virus. The data currently available are not sufficient to firmly assert whether SARS-CoV2 results from a zoonotic emergence or from an accidental escape of a laboratory strain. This question needs to be solved because it has important consequences on the risk/benefit balance of our interactions with ecosystems, on intensive breeding of wild and domestic animals, on some laboratory practices and on scientific policy and biosafety regulations. Regardless of COVID-19 origin, studying the evolution of the molecular mechanisms involved in the emergence of pandemic viruses is essential to develop therapeutic and vaccine strategies and to prevent future zoonoses. This article is a translation and update of a French article published in Médecine/Sciences, August/September 2020 (10.1051/medsci/2020123).Supplementary informationThe online version of this article (10.1007/s10311-020-01151-1) contains supplementary material, which is available to authorized users.
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Project description:BackgroundThe MLH1 gene is one of the DNA mismatch repair genes (MMR), implicated in Lynch syndrome (LS), an autosomal dominant hereditary tumor susceptibility disease. The advent of next-generation sequencing (NGS) technologies has accelerated the diagnosis of inherited diseases and increased the percentage of diagnosis of inherited cancers. However, some complex genomic alterations require the combination of several analytical strategies to allow correct biological interpretations. Here, we describe a novel MLH1 deletion and its pathogenicity determination in a patient suspected of LS.MethodsThe index case was a French 73-year-old man diagnosed with colorectal cancer displaying microsatellite instability and the loss of MLH1 and PMS2 expression. NGS analysis was used as the primary method for MMR genes screening. Long-range PCR and reverse transcriptase polymerase chain reaction (RT-PCR) were used for breakpoints and pathogenicity determinations.ResultsA large genomic deletion was detected which removed the last six nucleotides of MLH1 exon 11 together with a large part of intron 11. It was initially considered as a variant of unknown significance (VUS). Genomic breakpoints were subsequently characterized defining the deletion as c.1033_1039-248del. Further RNA analysis demonstrated that this variant activated a cryptic donor splice site at the 5' of the breakpoint, leading to a premature truncated protein: p.Thr345Alafs*13.ConclusionOur finding suggested that although NGS technologies have increased variant detection yield, combined approaches were still needed for complex variant characterization and pathogenicity assessment.
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