Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and ORF8 during the Early Evolution of SARS-CoV-2.,mBio

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Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and ORF8 during the Early Evolution of SARS-CoV-2.
mBio ( IF 5.1 ) Pub Date : 2020-07-21 , DOI: 10.1128/mbio.01610-20
Yvonne C F Su ₁ , Danielle E Anderson ₁ , Barnaby E Young _{2,

3,

4} , Martin Linster ₁ , Feng Zhu ₁ , Jayanthi Jayakumar ₁ , Yan Zhuang ₁ , Shirin Kalimuddin _{1,

5} , Jenny G H Low _{1,

5} , Chee Wah Tan ₁ , Wan Ni Chia ₁ , Tze Minn Mak ₂ , Sophie Octavia ₂ , Jean-Marc Chavatte ₂ , Raphael T C Lee ₆ , Surinder Pada ₇ , Seow Yen Tan ₈ , Louisa Sun ₉ , Gabriel Z Yan ₁₀ , Sebastian Maurer-Stroh _{6,

11} , Ian H Mendenhall _{1,

12} , Yee-Sin Leo _{2,

3,

4,

13,

14} , David Chien Lye _{2,

3,

4,

14} , Lin-Fa Wang _{12,

15,

16} , Gavin J D Smith _{12,

15,

16}

Affiliation

Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
National Centre for Infectious Diseases, Singapore.
Tan Tock Seng Hospital, Singapore.
Lee Kong Chian School of Medicine, Singapore.
Singapore General Hospital, Singapore.
Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
Ng Teng Fong General Hospital, Singapore.
Changi General Hospital, Singapore.
Alexandra Hospital, Singapore.
National University Hospital, Singapore.
Department of Biological Sciences, National University of Singapore, Singapore.
SingHealth Duke-NUS Global Health Institute, Singapore.
Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
Duke Global Health Institute, Duke University, North Carolina, USA.

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.

更新日期：2020-08-25

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