Comparison of SARS-CoV-2 variant lethality in human angiotensin-converting enzyme 2 transgenic mice

Virus Res. 2021 Nov:305:198563. doi: 10.1016/j.virusres.2021.198563. Epub 2021 Sep 14.

Abstract

This study compared the lethality of severe acute respiratory syndrome coronavirus 2 variants belonging to the S, V, L, G, GH, and GR clades using K18-human angiotensin-converting enzyme 2 heterozygous mice. To estimate the 50% lethal dose (LD50) of each variant, increasing viral loads (100-104 plaque-forming units [PFU]) were administered intranasally. Mouse weight and survival were monitored for 14 days. The LD50 of the GH and GR clades was significantly lower than that of other clades at 50 PFU. These findings suggest that the GH and GR clades, which are prevalent worldwide, are more virulent than the other clades.

Keywords: Genotype; K18-hACE2 transgenic mouse; Lethality; SARS-CoV-2.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2 / genetics*
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • Base Sequence
  • Body Weight
  • COVID-19 / mortality*
  • COVID-19 / pathology
  • COVID-19 / virology
  • Chlorocebus aethiops
  • Gene Expression
  • Humans
  • Lethal Dose 50
  • Male
  • Mice
  • Mice, Transgenic
  • Phylogeny
  • Receptors, Virus / genetics*
  • Receptors, Virus / metabolism
  • SARS-CoV-2 / classification
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / metabolism
  • SARS-CoV-2 / pathogenicity*
  • Severity of Illness Index
  • Survival Analysis
  • Transgenes
  • Vero Cells
  • Viral Load / genetics*
  • Viral Plaque Assay
  • Virulence

Substances

  • Receptors, Virus
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2