Population-Specific ACE2 Single-Nucleotide Polymorphisms Have Limited Impact on SARS-CoV-2 Infectivity In Vitro
| Autor: | Ayako Takashima, Gabriel Gonzalez, Masaharu Iwasaki, Mei Hashizume, Chikako Ono |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
viruses Nonsense mutation lcsh:QR1-502 ACE2 Single-nucleotide polymorphism Biology Molecular Dynamics Simulation Polymorphism Single Nucleotide lcsh:Microbiology 03 medical and health sciences 0302 clinical medicine Neutralization Tests Virology SNP Humans Receptor skin and connective tissue diseases Gene Infectivity Genetics SARS-CoV-2 Communication HEK 293 cells fungi COVID-19 Virus Internalization In vitro body regions 030104 developmental biology Infectious Diseases Genetics Population HEK293 Cells Amino Acid Substitution Mutagenesis 030220 oncology & carcinogenesis viral cell entry Receptors Virus Angiotensin-Converting Enzyme 2 hormones hormone substitutes and hormone antagonists SNPs Protein Binding |
| Zdroj: | Viruses Viruses, Vol 13, Iss 67, p 67 (2021) |
| ISSN: | 1999-4915 |
| Popis: | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), employs host-cell angiotensin-converting enzyme 2 (ACE2) for cell entry. Genetic analyses of ACE2 have identified several single-nucleotide polymorphisms (SNPs) specific to different human populations. Molecular dynamics simulations have indicated that several of these SNPs could affect interactions between SARS-CoV-2 and ACE2, thereby providing a partial explanation for the regional differences observed in SARS-CoV-2 infectivity and severity. However, the significance of population-specific ACE2 SNPs in SARS-CoV-2 infectivity is unknown, as no in vitro validation studies have been performed. Here, we analyzed the impact of eight SNPs found in specific populations on receptor binding and cell entry in vitro. Except for a SNP causing a nonsense mutation that reduced ACE2 expression, none of the selected SNPs markedly altered the interaction between ACE2 and the SARS-CoV-2 spike protein (SARS-2-S), which is responsible for receptor recognition and cell entry, or the efficiency of viral cell entry mediated by SARS-2-S. Our findings indicate that ACE2 polymorphisms have limited impact on the ACE2-dependent cell entry of SARS-CoV-2 and underscore the importance of future studies on the involvement of population-specific SNPs of other host genes in susceptibility toward SARS-CoV-2 infection. |
| Databáze: | OpenAIRE |
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