Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France
During routine molecular surveillance of SARS-CoV-2 performed at the National Reference Center of Respiratory Viruses (Lyon, France) (n = 229 sequences collected February–April 2020), two frameshifting deletions were detected in the open reading frame 6, at the same position (27267). While a 26-nucl...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
|
| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2021.1872351 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850032017399349248 |
|---|---|
| author | Grégory Quéromès Grégory Destras Antonin Bal Hadrien Regue Gwendolyne Burfin Solenne Brun Rémi Fanget Florence Morfin Martine Valette Sophie Trouillet-Assant Bruno Lina Emilie Frobert Laurence Josset |
| author_facet | Grégory Quéromès Grégory Destras Antonin Bal Hadrien Regue Gwendolyne Burfin Solenne Brun Rémi Fanget Florence Morfin Martine Valette Sophie Trouillet-Assant Bruno Lina Emilie Frobert Laurence Josset |
| author_sort | Grégory Quéromès |
| collection | DOAJ |
| description | During routine molecular surveillance of SARS-CoV-2 performed at the National Reference Center of Respiratory Viruses (Lyon, France) (n = 229 sequences collected February–April 2020), two frameshifting deletions were detected in the open reading frame 6, at the same position (27267). While a 26-nucleotide deletion variant (D26) was only found in one nasopharyngeal sample in March 2020, the 34-nucleotide deletion (D34) was found within a single geriatric hospital unit in 5/9 patients and one health care worker in April 2020. Phylogeny analysis strongly suggested a nosocomial transmission of D34, with potential fecal transmission, as also identified in a stool sample. No difference in disease severity was observed between patients hospitalized in the geriatric unit infected with WT or D34. In vitro D26 and D34 characterization revealed comparable replication kinetics with the wild-type (WT), but differential host immune responses. While interferon-stimulated genes were similarly upregulated after infection with WT and ORF6 variants, the latter specifically induced overexpression of 9 genes coding for inflammatory cytokines in the NF-kB pathway, including CCL2/MCP1, PTX3, and TNFα, for which high plasma levels have been associated with severe COVID-19. Our findings emphasize the need to monitor the occurrence of ORF6 deletions and assess their impact on the host immune response. |
| format | Article |
| id | doaj-art-d578fc65da364b60b22387d9bb62fa12 |
| institution | DOAJ |
| issn | 2222-1751 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-d578fc65da364b60b22387d9bb62fa122025-08-20T02:58:47ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512021-01-0110116717710.1080/22221751.2021.1872351Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, FranceGrégory Quéromès0Grégory Destras1Antonin Bal2Hadrien Regue3Gwendolyne Burfin4Solenne Brun5Rémi Fanget6Florence Morfin7Martine Valette8Sophie Trouillet-Assant9Bruno Lina10Emilie Frobert11Laurence Josset12CIRI, Centre International de Recherche en Infectiologie, Team VirPatH, Lyon, FracneCIRI, Centre International de Recherche en Infectiologie, Team VirPatH, Lyon, FracneCIRI, Centre International de Recherche en Infectiologie, Team VirPatH, Lyon, FracneLaboratoire de Virologie, Institut des Agents Infectieux (IAI), Hospices Civils de Lyon, Lyon, FranceLaboratoire de Virologie, Institut des Agents Infectieux (IAI), Hospices Civils de Lyon, Lyon, FranceLaboratoire de Virologie, Institut des Agents Infectieux (IAI), Hospices Civils de Lyon, Lyon, FranceLaboratoire de Virologie, Institut des Agents Infectieux (IAI), Hospices Civils de Lyon, Lyon, FranceCIRI, Centre International de Recherche en Infectiologie, Team VirPatH, Lyon, FracneCIRI, Centre International de Recherche en Infectiologie, Team VirPatH, Lyon, FracneCIRI, Centre International de Recherche en Infectiologie, Team VirPatH, Lyon, FracneCIRI, Centre International de Recherche en Infectiologie, Team VirPatH, Lyon, FracneCIRI, Centre International de Recherche en Infectiologie, Team VirPatH, Lyon, FracneCIRI, Centre International de Recherche en Infectiologie, Team VirPatH, Lyon, FracneDuring routine molecular surveillance of SARS-CoV-2 performed at the National Reference Center of Respiratory Viruses (Lyon, France) (n = 229 sequences collected February–April 2020), two frameshifting deletions were detected in the open reading frame 6, at the same position (27267). While a 26-nucleotide deletion variant (D26) was only found in one nasopharyngeal sample in March 2020, the 34-nucleotide deletion (D34) was found within a single geriatric hospital unit in 5/9 patients and one health care worker in April 2020. Phylogeny analysis strongly suggested a nosocomial transmission of D34, with potential fecal transmission, as also identified in a stool sample. No difference in disease severity was observed between patients hospitalized in the geriatric unit infected with WT or D34. In vitro D26 and D34 characterization revealed comparable replication kinetics with the wild-type (WT), but differential host immune responses. While interferon-stimulated genes were similarly upregulated after infection with WT and ORF6 variants, the latter specifically induced overexpression of 9 genes coding for inflammatory cytokines in the NF-kB pathway, including CCL2/MCP1, PTX3, and TNFα, for which high plasma levels have been associated with severe COVID-19. Our findings emphasize the need to monitor the occurrence of ORF6 deletions and assess their impact on the host immune response.https://www.tandfonline.com/doi/10.1080/22221751.2021.1872351SARS-CoV-2ORF6deletiongenomic surveillancenosocomial clusterinflammation |
| spellingShingle | Grégory Quéromès Grégory Destras Antonin Bal Hadrien Regue Gwendolyne Burfin Solenne Brun Rémi Fanget Florence Morfin Martine Valette Sophie Trouillet-Assant Bruno Lina Emilie Frobert Laurence Josset Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France Emerging Microbes and Infections SARS-CoV-2 ORF6 deletion genomic surveillance nosocomial cluster inflammation |
| title | Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France |
| title_full | Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France |
| title_fullStr | Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France |
| title_full_unstemmed | Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France |
| title_short | Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France |
| title_sort | characterization of sars cov 2 orf6 deletion variants detected in a nosocomial cluster during routine genomic surveillance lyon france |
| topic | SARS-CoV-2 ORF6 deletion genomic surveillance nosocomial cluster inflammation |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2021.1872351 |
| work_keys_str_mv | AT gregoryqueromes characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance AT gregorydestras characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance AT antoninbal characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance AT hadrienregue characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance AT gwendolyneburfin characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance AT solennebrun characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance AT remifanget characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance AT florencemorfin characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance AT martinevalette characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance AT sophietrouilletassant characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance AT brunolina characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance AT emiliefrobert characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance AT laurencejosset characterizationofsarscov2orf6deletionvariantsdetectedinanosocomialclusterduringroutinegenomicsurveillancelyonfrance |