OmniVira

Literature detail

Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants.

Yali Zhang1,2 Min Wei1,2 Yangtao Wu1,2 Juan Wang1,2 Yuting Hong1,2 Yang Huang1,2 Lunzhi Yuan1,2 Jian Ma1,2 Kai Wang1,2 Shaojuan Wang1,2 Yang Shi1,2 Zikang Wang1,2 Huilin Guo1,2 Jin Xiao1,2 Chuanlai Yang1,2 Jianghui Ye1,2 Jijing Chen1,2 Yuxi Liu1,2 Baorong Fu1,2 Miaolin Lan1,2 Peixuan Gong1,2 Zehong Huang1,2 Yingying Su1,2 Yixin Chen1,2 Tianying Zhang1,2 Jun Zhang1,2 Huachen Zhu3,4 Hai Yu1,5 Quan Yuan1,6 Tong Cheng1,7 Yi Guan3,8 Ningshao Xia1,9,10
Affiliations 10 institutions
  1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, P.R. China
  2. National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, P.R. China.
  3. State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, P.R. China
  4. Joint Institute of Virology (Shantou University and The University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, P.R. China.
  5. National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, P.R. China. Electronic address: [email protected].
  6. National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, P.R. China. Electronic address: [email protected].
  7. National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, P.R. China. Electronic address: [email protected].
  8. Joint Institute of Virology (Shantou University and The University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, P.R. China. Electronic address: [email protected].
  9. National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, P.R. China
  10. Research Unit of Frontier Technology of Structural Vaccinology, Chinese Academy of Medical Sciences, Xiamen University, Xiamen, P.R. China. Electronic address: [email protected].
PMID 35303476 2022 Cell Rep eng ppublish
PubMed DOI Browse context

Article

Publication summary

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) may alter viral host tropism and affect the activities of neutralizing antibodies. Here, we investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs) (including Omicron) for their antigenic changes and cross-species tropism in cells expressing 18 ACE2 orthologs. Several RBD mutations strengthened viral infectivity in cells expressing ACE2 orthologs of non-human animals, particularly those less susceptible to the ancestral strain. The mutations surrounding amino acids (aas) 439-448 and aa 484 are more likely to cause neutralization resistance. Strikingly, enhanced cross-species infection potential in the mouse and ferret, instead of the neutralization-escape scores of the mutations, account for the positive correlation with the cumulative prevalence of mutations in humans. These findings present insights for potential drivers of circulating SARS-CoV-2 variants and provide informative parameters for tracking and forecasting spreading mutations.

ACE2 receptor CP: Immunology CP: Microbiology cross-species tropism neutralization resistance RBD mutations SARS-CoV-2 variants variants of concern variants of interest COVID-19 SARS-CoV-2 Animals Ferrets Humans Membrane Glycoproteins Mice Spike Glycoprotein, Coronavirus Tropism

Structured evidence records

Evidence records

7 total
Molecular Adaptation 2 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Specific SARS-CoV-2 spike RBD mutations enhanced infectivity via ACE2 orthologs from non-human species, indicating molecular adaptation for cross-species infection potential.

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

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) may alter viral host tropism and affect the activities of neutralizing antibodies. Several RBD mutations strengthened viral infectivity in cells expressing ACE2 orthologs of non-human animals, particularly those less susceptible to the ancestral strain.

Genes or proteins
spike; RBD
Receptors
ACE2
Mechanism types
receptor_binding; cross_species_adaptation; tropism; infectivity
Molecular Adaptation Extraction confidence 0.90
Key finding

Mutations near spike RBD residues 439–448 and 484 conferred neutralization resistance, indicating adaptive immune-escape changes in SARS-CoV-2.

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

The mutations surrounding amino acids (aas) 439-448 and aa 484 are more likely to cause neutralization resistance.

Genes or proteins
spike; RBD
Mutations
aa 439-448 region; aa 484
Mechanism types
immune_escape; antigenic_change
Receptor Usage 2 records
Receptor Usage Extraction confidence 0.90
Key finding

SARS-CoV-2 spike receptor-binding domain mutations modulate infectivity via ACE2 receptor orthologs, increasing entry efficiency in cells expressing mouse and ferret ACE2.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

We investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs) ... for their antigenic changes and cross-species tropism in cells expressing 18 ACE2 orthologs. Several RBD mutations strengthened viral infectivity in cells expressing ACE2 orthologs of non-human animals.

Method
cell infectivity assay
Receptors
ACE2
Receptor Usage Extraction confidence 0.90
Key finding

Specific SARS-CoV-2 RBD mutations enhance receptor-mediated infectivity through ferret ACE2 orthologs.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Enhanced cross-species infection potential in the mouse and ferret ... account for the positive correlation with the cumulative prevalence of mutations in humans.

Method
cell infectivity assay
Receptors
ACE2
Cross Species Transmission 1 records
Cross Species Transmission Extraction confidence 0.90
Key finding

SARS-CoV-2 variants showed enhanced infection potential in mouse and ferret ACE2-expressing cells, indicating cross-species transmission capability between non-human animals.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Enhanced cross-species infection potential in the mouse and ferret accounted for the positive correlation with the cumulative prevalence of mutations in humans.

Method
ACE2 ortholog expression assay; infectivity test
Study design
cell-based tropism experiment
Transmission direction
animal-to-animal
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.70
Key finding

Sequence analysis of SARS-CoV-2 spike RBD mutations revealed evolution of circulating variants with enhanced cross-species infectivity and changes in amino acid regions 439–448 and 484.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) may alter viral host tropism... We investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs).

Genes or proteins
spike; receptor-binding domain; RBD
Analysis methods
mutation analysis
Host Range Experiment 1 records
Host Range Experiment Extraction confidence 0.85
Key finding

SARS-CoV-2 RBD mutations increased infectivity in cells expressing non-human ACE2 orthologs, notably from mouse and ferret, indicating expanded experimental host range.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

We investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs) (including Omicron) for their antigenic changes and cross-species tropism in cells expressing 18 ACE2 orthologs. Several RBD mutations strengthened viral infectivity in cells expressing ACE2 orthologs of non-human animals, particularly those less susceptible to the ancestral strain.

Method
cell-entry assay; infectivity assay
Experimental system
in vitro cell culture