Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Queromes G

PROVIDER: S-EPMC7850418 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:It is becoming widely accepted that epigenetic alterations are universally present in human malignancies and that cancer is as much a disease of abnormal epigenetics as it is a genetic disease. The potential utility of epigenetics and epigenomics in cancer research and cancer control is highlighted by the fact that many funding agencies put cancer epigenetics on the priority list. The goal of this meeting, held at the offices of the International Agency for Research on Cancer in Lyon, France, 6 and 7 December 2007, was to discuss recent conceptual and technological advances in cancer epigenetics and epigenomics, the future research needs in the field, and their implications for early detection, risk assessment and prevention of cancer. While epigenetics has been historically linked to phenomena that do not follow normal genetic principles of heritability, recent mechanistic advances have begun to change our understanding of complex diseases including cancer, traditionally viewed as genetic in origin. It is now known that epigenetic mechanisms play critical roles in regulation of many cellular functions and their deregulation may disrupt the control of fundamental processes leading to tumour formation. A flurry of screening and functional studies revealed that most key processes found in cancer cells, such as silencing of tumour suppressor genes, activation of oncogenes, aberrant cell cycle processes, defects in DNA repair, and deregulation of cell death, can be triggered by epigenetic deregulation. Two important features that distinguish epigenetic changes from genetic alterations are the gradual appearance and reversibility of epigenetic events. These features make epigenetic alterations an attractive target for therapeutic intervention and the development of preventive strategies. For example, aberrant patterns of DNA methylation and histone acetylation and methylation can be targeted by drugs aiming to re-activate epigenetically silenced genes. Until now, most studies on epigenetic changes in cancer were generally focused on specific genes. However, this meeting also stressed the need to take advantage of recent progress in epigenomics and emergence of powerful technologies for detection of epigenetic changes in high throughput and genome-wide settings. This may further advance our capacity to evaluate the contribution of epigenetic changes induced by environmental epimutagens to human cancer. This information may prove critical for the design of efficient strategies for early diagnosis, therapy, and prevention of cancer.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets