Coronavirus MHV-A59 infects the lung and causes severe pneumonia in C57BL/6 mice
Zhangsheng Yang1, Jun Du, Gang Chen
1Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing, 100101, China.
Abstract:
It remains challenging to develop animal models of lung infection and severe pneumonia by severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome cornavirus (MERS-CoV) without high level of containment. This inevitably hinders understanding of virushost interaction and development of appropriate countermeasures. Here we report that intranasal inoculation of sublethal doses of murine coronavirus mouse hepatitis virus A-59 (MHV-A59), a hepatic and neuronal tropic coronavirus, can induce acute pneumonia and severe lung injuries in C57BL/6 mice. Inflammatory leukocyte infiltrations, hemorrhages and fibrosis of alveolar walls can be observed 2-11 days after MHV-A59 infection. This pathological manifestation is associated with dramatical elevation of tissue IP-10 and IFN-γ and moderate increase of TNF-α and IL-1β, but inability of anti-viral type I interferon response. These results suggest that intranasal infection of MHV-A59 would serve as a surrogate mouse model of acute respiratory distress syndrome by SARS-CoV and MERS-CoV infections.
Insights
Developing animal models for severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) lung infections is difficult. Mouse hepatitis virus A-59 (MHV-A59) in mice offers a viable surrogate model for studying these severe respiratory diseases.
Area of Science:
- Virology
- Pathology
- Immunology
Background:
- Developing animal models for SARS-CoV and MERS-CoV lung infections requires high containment, hindering research.
- Understanding virus-host interactions and developing countermeasures are crucial for combating these diseases.
Purpose of the Study:
- To establish a suitable animal model for studying severe respiratory coronaviruses.
- To investigate the potential of mouse hepatitis virus A-59 (MHV-A59) as a surrogate model for SARS-CoV and MERS-CoV induced lung injury.
Main Methods:
- Intranasal inoculation of sublethal doses of MHV-A59 into C57BL/6 mice.
- Histopathological analysis of lung tissues to assess inflammation, hemorrhage, and fibrosis.
- Measurement of key inflammatory cytokines (IP-10, IFN-γ, TNF-α, IL-1β) and type I interferon response.
Main Results:
- MHV-A59 infection induced acute pneumonia and severe lung injuries, including inflammatory leukocyte infiltration, hemorrhages, and alveolar wall fibrosis.
- Pathological changes were observed between 2-11 days post-infection.
- Infection led to elevated IP-10 and IFN-γ, with moderate increases in TNF-α and IL-1β, but a suppressed type I interferon response.
Conclusions:
- Intranasal MHV-A59 infection in C57BL/6 mice effectively models acute pneumonia and lung injury.
- This MHV-A59 mouse model serves as a valuable surrogate for studying severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infections.
- The model facilitates research into virus-host interactions and the development of therapeutic strategies for severe respiratory viral diseases.
