Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France

Quéromès, Grégory; Destras, Grégory; Bal, Antonin; Regue, Hadrien; Burfin, Gwendolyne; Brun, Solenne; Fanget, Rémi; Morfin, Florence; Valette, Martine; Trouillet‐Assant, Sophie; Lina, Bruno; Frobert, Émilie; Josset, Laurence

doi:10.1080/22221751.2021.1872351

Cited by 32 publications

(21 citation statements)

References 54 publications

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“…A study by Zhang et al conducted in China showed no significant differences between two variants (clade I (ORF3a: p.251G > V, or S: p.614D > G (subclade G)); clade II (ORF8: p.84L > S (28,144U > C) and ORF1ab: p.2839S (8782C > U)) regarding disease severity and blood parameters indicative of severity [24]. No significant difference in clinical presentation was observed between hospitalized patients harboring or not harboring the D26 and D34 variants in the ORF6 protein [48]. A study conducted on isolates from patients in Washington, US, allowed the identification of two major clades distinguished by twelve polymorphisms in five genes.…”

Section: Relation Between Viral Mutations and Severity Of Covid-19 Infectionmentioning

confidence: 93%

“…Of the 63 publications included, five were non-peer reviewed preprints [16,17,52,54,66]. Eleven articles reported in vitro, in silico or animal model studies [15,18,19,[22][23][24][25][26][27][28][29]; nineteen articles reported clinical studies [16,[37][38][39][41][42][43][44][45][46][47][48][49]51,[70][71][72][73]. The remaining 33 articles analyzed SARS-CoV-2 genomes downloaded from the GISAID or other available databases with patient status [8][9][10][11]20,21,[30][31][32][33][34][35][36]40,50,…”

Section: Study Selection and Types Of Studiesmentioning

confidence: 99%

“…A total of 45 articles addressed the effect of viral mutations on severity of COVID-19 in patients, of which fifteen studies (five bigdata analyses [21,30,33,34,40] and ten clinical studies [39,[41][42][43][44][45][46][47][48][49]) showed no association between SARS-CoV-2 variants and severity of disease. Three studies (one bigdata analysis [50] and two clinical studies [17,51]) reported that the SARS-CoV-2 variants were significantly associated with decrease in severity of disease.…”

Section: Relation Between Viral Mutations and Severity Of Covid-19 Infectionmentioning

confidence: 99%

See 2 more Smart Citations

SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

Dao

Hoang

Colson

et al. 2021

JCM

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Background: We conducted this review to summarize the relation between viral mutation and infectivity of SARS-CoV-2 and also the severity of COVID-19 in vivo and in vitro. Method: Articles were identified through a literature search until 31 May 2021, in PubMed, Web of Science and Google Scholar. Results: Sixty-three studies were included. To date, most studies showed that the viral mutations, especially the D614G variant, correlate with a higher infectivity than the wild-type virus. However, the evidence of the association between viral mutation and severity of the disease is scant. A SARS-CoV-2 variant with a 382-nucleotide deletion was associated with less severe infection in patients. The 11,083G > U mutation was significantly associated with asymptomatic patients. By contrast, ORF1ab 4715L and S protein 614G variants were significantly more frequent in patients from countries where high fatality rates were also reported. The current evidence showed that variants of concern have led to increased infectivity and deteriorating epidemiological situations. However, the relation between this variant and severity of COVID-19 infection was contradictory. Conclusion: The COVID-19 pandemic continues to spread worldwide. It is necessary to anticipate large clinical cohorts to evaluate the virulence and transmissibility of SARS-CoV-2 mutants.

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Section: Relation Between Viral Mutations and Severity Of Covid-19 Infectionmentioning

confidence: 93%

Section: Study Selection and Types Of Studiesmentioning

confidence: 99%

Section: Relation Between Viral Mutations and Severity Of Covid-19 Infectionmentioning

confidence: 99%

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SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

Dao

Hoang

Colson

et al. 2021

JCM

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“…These accessory ORFs has been demonstrated to play a role in modulating the immune response from the host (Lei et al, 2020) and can disrupt host cell signaling capacity suppressing STAT1/2 phosphorylation, inhibiting interferon gamma mediated response, and causing immune evasion (Xia et al, 2020). Population-fixed variants can disrupt these ORFs by creating new stop codons, a phenomenon already demonstrated for ORF3a (Lam et al, 2020), ORF6 (Queromes et al, 2021) and ORF8 (Gong et al, 2020;Ngernmuen et al, 2020;Flower et al, 2021) amongst other ORFs. Also, variants toward the 3 UTR of the virus can confer resistance to host miRNA viral targeting since several human miRNAs are predicted to prevent virus replication by binding to this untranslated region (Chen and Zhong, 2020;Mukherjee and Goswami, 2020).…”

Section: Introductionmentioning

confidence: 93%

A Novel SARS-CoV-2 Viral Sequence Bioinformatic Pipeline Has Found Genetic Evidence That the Viral 3′ Untranslated Region (UTR) Is Evolving and Generating Increased Viral Diversity

et al. 2021

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An unprecedented amount of SARS-CoV-2 sequencing has been performed, however, novel bioinformatic tools to cope with and process these large datasets is needed. Here, we have devised a bioinformatic pipeline that inputs SARS-CoV-2 genome sequencing in FASTA/FASTQ format and outputs a single Variant Calling Format file that can be processed to obtain variant annotations and perform downstream population genetic testing. As proof of concept, we have analyzed over 229,000 SARS-CoV-2 viral sequences up until November 30, 2020. We have identified over 39,000 variants worldwide with increased polymorphisms, spanning the ORF3a gene as well as the 3′ untranslated (UTR) regions, specifically in the conserved stem loop region of SARS-CoV-2 which is accumulating greater observed viral diversity relative to chance variation. Our analysis pipeline has also discovered the existence of SARS-CoV-2 hypermutation with low frequency (less than in 2% of genomes) likely arising through host immune responses and not due to sequencing errors. Among annotated non-sense variants with a population frequency over 1%, recurrent inactivation of the ORF8 gene was found. This was found to be present in the newly identified B.1.1.7 SARS-CoV-2 lineage that originated in the United Kingdom. Almost all VOC-containing genomes possess one stop codon in ORF8 gene (Q27∗), however, 13% of these genomes also contains another stop codon (K68∗), suggesting that ORF8 loss does not interfere with SARS-CoV-2 spread and may play a role in its increased virulence. We have developed this computational pipeline to assist researchers in the rapid analysis and characterization of SARS-CoV-2 variation.

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“…As for the ORF3a and ORF3b proteins, the ORF6 protein of SARS-CoV-2 presented a strong similarity with the ORF6 protein of SARS-CoV-1 and bat-CoV-SL-RmYN02 (68.9 and 70.5%, respectively), but even more with the ORF6 protein of the bat-SL-CoV-RaTG13 and Pangolin-CoV-2019 (100 and 96.7%) (Figure 4B and Supplementary Table 1). Recently, SARS-CoV-2 ORF6 deletion variants were isolated and characterized (26nt deletion and 34-nt deletion, respectively) (Quéromès et al, 2021) or carrying a nucleotide mutation leading to a stop codon in the ORF6 protein (Delbue et al, 2021). No significant difference in term of viral replication, as well as ISG expression, was observed between these two SARS-CoV-2 deletion variants and the reference strain.…”

Section: Orf6 Proteinmentioning

confidence: 99%

Coronavirus, the King Who Wanted More Than a Crown: From Common to the Highly Pathogenic SARS-CoV-2, Is the Key in the Accessory Genes?

Chazal

2021

Front. Microbiol.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that emerged in late 2019, is the etiologic agent of the current “coronavirus disease 2019” (COVID-19) pandemic, which has serious health implications and a significant global economic impact. Of the seven human coronaviruses, all of which have a zoonotic origin, the pandemic SARS-CoV-2, is the third emerging coronavirus, in the 21st century, highly pathogenic to the human population. Previous human coronavirus outbreaks (SARS-CoV-1 and MERS-CoV) have already provided several valuable information on some of the common molecular and cellular mechanisms of coronavirus infections as well as their origin. However, to meet the new challenge caused by the SARS-CoV-2, a detailed understanding of the biological specificities, as well as knowledge of the origin are crucial to provide information on viral pathogenicity, transmission and epidemiology, and to enable strategies for therapeutic interventions and drug discovery. Therefore, in this review, we summarize the current advances in SARS-CoV-2 knowledges, in light of pre-existing information of other recently emerging coronaviruses. We depict the specificity of the immune response of wild bats and discuss current knowledge of the genetic diversity of bat-hosted coronaviruses that promotes viral genome expansion (accessory gene acquisition). In addition, we describe the basic virology of coronaviruses with a special focus SARS-CoV-2. Finally, we highlight, in detail, the current knowledge of genes and accessory proteins which we postulate to be the major keys to promote virus adaptation to specific hosts (bat and human), to contribute to the suppression of immune responses, as well as to pathogenicity.

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Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France

Cited by 32 publications

References 54 publications

SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

A Novel SARS-CoV-2 Viral Sequence Bioinformatic Pipeline Has Found Genetic Evidence That the Viral 3′ Untranslated Region (UTR) Is Evolving and Generating Increased Viral Diversity

Coronavirus, the King Who Wanted More Than a Crown: From Common to the Highly Pathogenic SARS-CoV-2, Is the Key in the Accessory Genes?

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