Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and ORF8 during the Early Evolution of SARS-CoV-2.
Yvonne C. F. Su,Danielle E. Anderson,Barnaby Edward Young,Martin Linster,Feng Zhu,Jayanthi Jayakumar,Yan Zhuang,Shirin Kalimuddin,Shirin Kalimuddin,Jenny G. Low,Jenny G. Low,Chee Wah Tan,Wan Ni Chia,Tze Minn Mak,Sophie Octavia,Jean-Marc Chavatte,Raphael T.C. Lee,Surinder Pada,Seow Yen Tan,Louisa Sun,Gabriel Yan,Sebastian Maurer-Stroh,Sebastian Maurer-Stroh,Ian H. Mendenhall,Yee Sin Leo,David C. Lye,Lin-Fa Wang,Lin-Fa Wang,Gavin J. D. Smith,Gavin J. D. Smith +29 more
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TLDR
A robust antibody response to ORF8 has been observed in SARS-CoV-2 infection, suggesting that the emergence of ORF7b/8 deletions may be due to immune-driven selection and that further deletion variants may emerge during the sustained transmission of Sars-Cov-2 in humans.Abstract:
To date, limited genetic changes in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome have been described. Here, we report a 382-nucleotide (nt) deletion in SARS-CoV-2 that truncates open reading frame 7b (ORF7b) and ORF8, removing the ORF8 transcription regulatory sequence (TRS) and eliminating ORF8 transcription. The earliest 382-nt deletion variant was detected in Singapore on 29 January 2020, with the deletion viruses circulating in the country and accounting for 23.6% (45/191) of SARS-CoV-2 samples screened in this study. SARS-CoV-2 with the same deletion has since been detected in Taiwan, and other ORF7b/8 deletions of various lengths, ranging from 62 nt to 345 nt, have been observed in other geographic locations, including Australia, Bangladesh, and Spain. Mutations or deletions in ORF8 of SARS-CoV have been associated with reduced replicative fitness and virus attenuation. In contrast, the SARS-CoV-2 382-nt deletion viruses showed significantly higher replicative fitness in vitro than the wild type, while no difference was observed in patient viral load, indicating that the deletion variant viruses retained their replicative fitness. A robust antibody response to ORF8 has been observed in SARS-CoV-2 infection, suggesting that the emergence of ORF8 deletions may be due to immune-driven selection and that further deletion variants may emerge during the sustained transmission of SARS-CoV-2 in humans.IMPORTANCE During the SARS epidemic in 2003/2004, a number of deletions were observed in ORF8 of SARS-CoV, and eventually deletion variants became predominant, leading to the hypothesis that ORF8 was an evolutionary hot spot for adaptation of SARS-CoV to humans. However, due to the successful control of the SARS epidemic, the importance of these deletions for the epidemiological fitness of SARS-CoV in humans could not be established. The emergence of multiple SARS-CoV-2 strains with ORF8 deletions, combined with evidence of a robust immune response to ORF8, suggests that the lack of ORF8 may assist with host immune evasion. In addition to providing a key insight into the evolutionary behavior of SARS-CoV-2 as the virus adapts to its new human hosts, the emergence of ORF8 deletion variants may also impact vaccination strategies.read more
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Characteristics of SARS-CoV-2 and COVID-19
TL;DR: The basic virology of SARS-CoV-2 is described, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses.
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Coronavirus biology and replication: implications for SARS-CoV-2.
TL;DR: The first discoveries that shape the current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle are summarized and relate that to the knowledge of coronavirus biology.
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TL;DR: Analysis of epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus, suggest that this novel virus has been transferred from an animal source, such as bats.
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Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients.
Anthony T. Tan,Martin Linster,Chee Wah Tan,Nina Le Bert,Wan Ni Chia,Kamini Kunasegaran,Yan Zhuang,Christine Y.L. Tham,Adeline Chia,Gavin J. D. Smith,Barnaby Edward Young,Shirin Kalimuddin,Shirin Kalimuddin,Jenny G. Low,Jenny G. Low,David C. Lye,Lin-Fa Wang,Antonio Bertoletti,Antonio Bertoletti +18 more
TL;DR: In this article, the authors quantify SARS-CoV-2 viral RNA in the respiratory tract in parallel with antibodies and circulating T-cells specific for various structural (nucleoprotein [NP], membrane [M], ORF3a, and spike) and non-structural (ORF7/8, NSP7, and NSP13) proteins.
Journal ArticleDOI
Presence and infectivity of SARS-CoV-2 virus in wastewaters and rivers.
Sara Giordana Rimoldi,Fabrizio Stefani,Anna Gigantiello,Stefano Polesello,Francesco Comandatore,Davide Mileto,Mafalda Maresca,Concetta Longobardi,Alessandro Mancon,Francesca Romeri,Cristina Pagani,Francesca Cappelli,Claudio Roscioli,Lorenzo Moja,Maria Rita Gismondo,Franco Salerno +15 more
TL;DR: Risks for public health should be limited, although a precautionary approach to risk assessment is here advocated, giving the preliminary nature of the presented data.
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