Expansion of a SARS-CoV-2 Delta variant with an 872 nt deletion encompassing ORF7a , ORF7b and ORF8 , Poland, July to August 2021.
30 Sep 2021-Eurosurveillance (European Centre for Disease Prevention and Control)-Vol. 26, Iss: 39, pp 2100902
TL;DR: In this paper, the emergence of a SARS-CoV-2 Delta variant with a large 872 nt deletion was confirmed by Sanger and deep sequencing, which caused complete loss of ORF 7a, ORF7b, and ORF8 genes.
Abstract: Routine genomic surveillance on samples from COVID-19 patients collected in Poland during summer 2021 revealed the emergence of a SARS-CoV-2 Delta variant with a large 872 nt deletion. This change, confirmed by Sanger and deep sequencing, causes complete loss of ORF7a, ORF7b, and ORF8 genes. The index case carrying the deletion is unknown. The standard pipeline for sequencing may mask this deletion with a long stretch of N's. Effects of this deletion on phenotype or immune evasion needs further study.
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References
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Tan Tock Seng Hospital1, Nanyang Technological University2, Agency for Science, Technology and Research3, National University of Singapore4, Singapore General Hospital5, University Health System6, Ng Teng Fong General Hospital7, Changi General Hospital8, Alexandra Hospital9, Khoo Teck Puat Hospital10, Singapore Ministry of Health11
TL;DR: The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection and the observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines.
372 citations
TL;DR: Screening the viral proteins of SARS-CoV-2 found that the viral ORF6, ORF8 and nucleocapsid proteins were potential inhibitors of type I interferon signaling pathway, a key component for antiviral response of host innate immune.
338 citations
TL;DR: This study provides guidelines to assess the phylodynamic threshold and demonstrates that establishing this threshold constitutes a fundamental step for understanding the power and limitations of early data in outbreak genome surveillance.
Abstract: The ongoing SARS-CoV-2 outbreak marks the first time that large amounts of genome sequence data have been generated and made publicly available in near real time. Early analyses of these data revealed low sequence variation, a finding that is consistent with a recently emerging outbreak, but which raises the question of whether such data are sufficiently informative for phylogenetic inferences of evolutionary rates and time scales. The phylodynamic threshold is a key concept that refers to the point in time at which sufficient molecular evolutionary change has accumulated in available genome samples to obtain robust phylodynamic estimates. For example, before the phylodynamic threshold is reached, genomic variation is so low that even large amounts of genome sequences may be insufficient to estimate the virus's evolutionary rate and the time scale of an outbreak. We collected genome sequences of SARS-CoV-2 from public databases at eight different points in time and conducted a range of tests of temporal signal to determine if and when the phylodynamic threshold was reached, and the range of inferences that could be reliably drawn from these data. Our results indicate that by 2 February 2020, estimates of evolutionary rates and time scales had become possible. Analyses of subsequent data sets, that included between 47 and 122 genomes, converged at an evolutionary rate of about 1.1 × 10-3 subs/site/year and a time of origin of around late November 2019. Our study provides guidelines to assess the phylodynamic threshold and demonstrates that establishing this threshold constitutes a fundamental step for understanding the power and limitations of early data in outbreak genome surveillance.
282 citations
TL;DR: Wang et al. as discussed by the authors showed that SARS-CoV-2 infection leads to major histocompability complex class Ι (MHC-Ι) down-regulation both in vitro and in vivo.
Abstract: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has claimed over 2 million lives worldwide. Although the genetic sequences of SARS-CoV and SARS-CoV-2 have high homology, the clinical and pathological characteristics of COVID-19 differ significantly from those of SARS. How and whether SARS-CoV-2 evades (cellular) immune surveillance requires further elucidation. In this study, we show that SARS-CoV-2 infection leads to major histocompability complex class Ι (MHC-Ι) down-regulation both in vitro and in vivo. The viral protein encoded by open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all viral proteins, directly interacts with MHC-Ι molecules and mediates their down-regulation. In ORF8-expressing cells, MHC-Ι molecules are selectively targeted for lysosomal degradation via autophagy. Thus, SARS-CoV-2-infected cells are much less sensitive to lysis by cytotoxic T lymphocytes. Because ORF8 protein impairs the antigen presentation system, inhibition of ORF8 could be a strategy to improve immune surveillance.
226 citations
TL;DR: A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans but it remains unclear whether the deletion actually reflects adaptation to humans.
Abstract: A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. In spite of intense study, it remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (−29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor. Cells from cotton rat, goat, and sheep provided control scenarios that represent host systems in which SARS-CoV is neither endemic nor epidemic. Independent of the cell system, the truncation of ORF8 (29 nt deletion) decreased replication up to 23-fold. The effect was independent of the type I interferon response. The 29 nt deletion in SARS-CoV is a deleterious mutation acquired along the initial human-to-human transmission chain. The resulting loss of fitness may be due to a founder effect, which has rarely been documented in processes of viral emergence. These results have important implications for the retrospective assessment of the threat posed by SARS.
222 citations