Characterization of the Pathogenic Features of Multiple SARS-CoV-2 Pandemic Strains in Different Mouse Models

Area of Science:

• Virology
• Pathogenesis
• Immunology

Background:

• Understanding emerging SARS-CoV-2 strains is crucial for vaccine and drug development.
• Characterizing viral features in vitro and in vivo aids in predicting and combating viral infections.

Purpose of the Study:

• To comprehensively analyze the virological and pathogenic characteristics of eight SARS-CoV-2 strains, from wild-type to EG.5.1.
• To compare the tropism and pathogenicity of different SARS-CoV-2 variants in various mouse models.
• To investigate the factors influencing viral infectivity, including host receptor affinity and immunocompetence.

Main Methods:

• In vitro virological characterization in Vero E6 cells.
• In vivo pathogenicity studies in K18 hACE2, C57BL/6JGpt, and BKS-db mice.
• Bioinformatic analysis of viral receptor-binding domains (RBDs) and host ACE2 interactions.

Main Results:

• Omicron variants (BA.1 to EG.5.1) demonstrated enhanced upper respiratory tract infection in K18 hACE2 mice.
• XBB.1.9.1 and EG.5.1 showed increased brain tropism, correlating with higher lethality in mice.
• Omicron BA.1, XBB.1.9.1, and EG.5.1 exhibited dual tropism for human and mouse ACE2 receptors.
• Immunocompromised BKS-db mice were more susceptible to Omicron strains than C57BL/6JGpt mice.

Conclusions:

• SARS-CoV-2 variant infectivity is influenced by both viral affinity to host ACE2 and host immunocompetence.
• This study provides a systematic understanding of SARS-CoV-2 pathogenesis in mice.
• Findings offer insights for developing strategies against future SARS-CoV-2 variant surges.