Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has caused global health and economic crises.
• Lack of effective mouse models hinders understanding of Coronavirus Disease 2019 (COVID-19) pathogenesis.
• Existing models do not fully recapitulate human disease or variant characteristics.

Purpose of the Study:

• To develop a novel mouse-adapted SARS-CoV-2 strain for robust disease modeling.
• To incorporate key mutations from SARS-CoV-2 variants into the adapted strain.
• To evaluate the utility of this model for studying viral infection, disease, and cross-protective immunity.

Main Methods:

• Generation of a mouse-adapted SARS-CoV-2 strain (CMA3p20) using reverse genetics.
• Incorporation of mutations found in SARS-CoV-2 variants of concern.
• Assessment of viral replication, immune response, and disease in mice.
• Evaluation of cross-protection against original Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV).

Main Results:

• The mouse-adapted strain (CMA3p20) replicates effectively in mouse lungs, causing significant disease.
• The model recapitulates key aspects of human SARS-CoV-2 infection, including immune cell infiltration.
• Mouse adaptation preserves replication in human airway cells and maintains antigenicity.
• Mice infected with the adapted strain showed protection against lethal SARS-CoV challenge, indicating heterologous immunity.

Conclusions:

• The developed mouse model (CMA3p20) is a valuable tool for studying SARS-CoV-2 pathogenesis and host responses.
• This model facilitates research into variant-specific mutations and their impact on disease.
• The findings suggest potential for cross-protective immunity between different coronavirus strains, warranting further investigation.