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C1qa deficiency in mice increases susceptibility to mouse hepatitis virus A59 infection
Han Woong Kim1,2, Sun Min Seo1, Jun Young Kim1,3
1Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.
Background:
Mouse hepatitis virus (MHV) A59 is a highly infectious pathogen and starts in the respiratory tract and progresses to systemic infection in laboratory mice. The complement system is an important part of the host immune response to viral infection. It is not clear the role of the classical complement pathway in MHV infection.
Objectives:
The purpose of this study was to determine the importance of the classical pathway in coronavirus pathogenesis by comparing C1qa KO mice and wild-type mice.
Methods:
We generated a C1qa KO mouse using CRISPR/Cas9 technology and compared the susceptibility to MHV A59 infection between C1qa KO and wild-type mice. Histopathological and immunohistochemical changes, viral loads, and chemokine expressions in both mice were measured.
Results:
MHV A59-infected C1qa KO mice showed severe histopathological changes, such as hepatocellular necrosis and interstitial pneumonia, compared to MHV A59-infected wild-type mice. Virus copy numbers in the olfactory bulb, liver, and lungs of C1qa KO mice were significantly higher than those of wild-type mice. The increase in viral copy numbers in C1qa KO mice was consistent with the histopathologic changes in organs. These results indicate that C1qa deficiency enhances susceptibility to MHV A59 systemic infection in mice. In addition, this enhanced susceptibility effect is associated with dramatic elevations in spleen IFN-γ, MIP-1 α, and MCP-1 in C1qa KO mice.
Conclusions:
These data suggest that C1qa deficiency enhances susceptibility to MHV A59 systemic infection, and activation of the classical complement pathway may be important for protecting the host against MHV A59 infection.
Insights
Mice lacking C1qa, a component of the classical complement pathway, showed increased susceptibility to Mouse Hepatitis Virus (MHV) A59 infection. This highlights the classical complement pathway's protective role against MHV systemic disease.
Area of Science:
- Immunology
- Virology
- Complement System
Background:
- Mouse hepatitis virus (MHV) A59 causes respiratory and systemic infections in mice.
- The complement system is crucial for immune response, but its role in MHV infection is unclear.
- The classical complement pathway's function in coronavirus pathogenesis requires investigation.
Purpose of the Study:
- To determine the significance of the classical complement pathway in coronavirus pathogenesis.
- To compare MHV A59 infection susceptibility between C1qa knockout (KO) and wild-type mice.
Main Methods:
- Generated C1qa KO mice using CRISPR/Cas9 technology.
- Compared MHV A59 infection in C1qa KO and wild-type mice.
- Assessed histopathology, viral loads, and chemokine expression.
Main Results:
- C1qa KO mice exhibited more severe histopathological changes, including necrosis and pneumonia.
- Significantly higher viral loads were observed in olfactory bulb, liver, and lungs of C1qa KO mice.
- Elevated spleen IFN-γ, MIP-1α, and MCP-1 were noted in C1qa KO mice.
Conclusions:
- C1qa deficiency enhances susceptibility to MHV A59 systemic infection.
- Classical complement pathway activation is important for host protection against MHV A59.
- This study elucidates the role of the classical complement pathway in MHV pathogenesis.
