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Literature detail

Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction.

Siu-Ying Lau1 Pui Wang1 Bobo Wing-Yee Mok1 Anna Jinxia Zhang1 Hin Chu1 Andrew Chak-Yiu Lee1 Shaofeng Deng1 Pin Chen1 Kwok-Hung Chan1 Wenjun Song1,2 Zhiwei Chen1 Kelvin Kai-Wang To1 Jasper Fuk-Woo Chan1 Kwok-Yung Yuen1 Honglin Chen1
Affiliations 2 institutions
  1. Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
  2. State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People's Republic of China.
PMID 32301390 2020 Emerg Microbes Infect eng ppublish
PubMed DOI Browse context

Article

Publication summary

The emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests the possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect these variants. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variants as an attenuated vaccine or laboratory tool should be evaluated.

Coronavirus COVID-19 SARS-CoV-2 Spike mutant Spike S1/S2 mutant Disease Models, Animal Mesocricetus Sequence Deletion Amino Acid Sequence Animals Base Sequence Cell Line Chlorocebus aethiops Coronavirus Infections COVID-19 Female Host Specificity Humans

Structured evidence records

Evidence records

3 total
Host Range Experiment 2 records
Host Range Experiment Extraction confidence 0.88
Key finding

Hamsters experimentally infected with a SARS-CoV-2 variant containing an S1/S2 junction deletion exhibited attenuated disease compared with wild-type infection, indicating altered host pathogenicity.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection.

Method
experimental infection
Sample type
lungs
Experimental system
in vivo animal experiment
Host Range Experiment Extraction confidence 0.88
Key finding

Replication of SARS-CoV-2 in Vero-E6 cells generated variants with deletions at the S1/S2 junction, suggesting adaptation during cell culture replication.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction.

Method
virus isolation; replication assay
Experimental system
in vitro cell culture
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

SARS-CoV-2 variants with deletions at the spike S1/S2 cleavage junction lose pathogenicity in hamsters, indicating that the cleavage motif is an adaptive feature essential for efficient human infection.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function.

Genes or proteins
spike; S1/S2 junction
Mutations
15-30-bp deletions; Del-mut-1 10 amino acid deletion
Mechanism types
pathogenicity; replication_efficiency; host_adaptation