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Updated: Aug 2, 2025
Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin
Published on: March 10, 2021
MHC class I links with severe pathogenicity in C57BL/6N mice infected with SARS-CoV-2/BMA8
Tian Qin1,2, Beilei Shen2, Entao Li3
1School of life sciences, Northeast Normal University, Changchun, 130024, China.
Background:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes non-symptomatic infection, mild influenza-like symptoms to pneumonia, severe acute respiratory distress syndrome, and even death, reflecting different clinical symptoms of viral infection. However, the mechanism of its pathogenicity remains unclear. Host-specific traits have a breakthrough significance for studying the pathogenicity of SARS-CoV-2. We previously reported SARS-CoV-2/BMA8, a mouse-adapted strain, was lethal to aged BALB/c mice but not to aged C57BL/6N mice. Here, we further investigate the differences in pathogenicity of BMA8 strain against wild-type aged C57BL/6N and BALB/c mice.
Methods:
Whole blood and tissues were collected from mice before and after BMA8 strain infection. Viral replication and infectivity were assessed by detection of viral RNA copies and viral titers; the degree of inflammation in mice was tested by whole blood cell count, ELISA and RT-qPCR assays; the pathogenicity of SARS-CoV-2/BMA8 in mice was measured by Histopathology and Immunohistochemistry; and the immune level of mice was evaluated by flow cytometry to detect the number of CD8+ T cells.
Results:
Our results suggest that SARS-CoV-2/BMA8 strain caused lower pathogenicity and inflammation level in C57BL/6N mice than in BALB/c mice. Interestingly, BALB/c mice whose MHC class I haplotype is H-2Kd showed more severe pathogenicity after infection with BMA8 strain, while blockade of H-2Kb in C57BL/6N mice was also able to cause this phenomenon. Furthermore, H-2Kb inhibition increased the expression of cytokines/chemokines and accelerated the decrease of CD8+ T cells caused by SARS-CoV-2/BMA8 infection.
Conclusions:
Taken together, our work shows that host MHC molecules play a crucial role in the pathogenicity differences of SARS-CoV-2/BMA8 infection. This provides a more profound insight into the pathogenesis of SARS-CoV-2, and contributes enlightenment and guidance for controlling the virus spread.
Insights
Host MHC molecules significantly influence SARS-CoV-2 pathogenicity differences. This study reveals how specific MHC class I haplotypes impact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection severity in mice.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits varied clinical presentations, but its pathogenicity mechanisms remain unclear.
- Host genetic factors are critical for understanding SARS-CoV-2 pathogenicity.
- A mouse-adapted SARS-CoV-2 strain (BMA8) showed differential lethality in aged BALB/c versus C57BL/6N mice.
Purpose of the Study:
- To investigate the differential pathogenicity of the SARS-CoV-2/BMA8 strain in aged wild-type C57BL/6N and BALB/c mice.
- To elucidate the role of host-specific traits, particularly MHC molecules, in SARS-CoV-2 infection outcomes.
Main Methods:
- Viral replication and infectivity were quantified using viral RNA copies and titers.
- Inflammation was assessed via blood cell counts, ELISA, and RT-qPCR.
- Pathogenicity was evaluated through histopathology and immunohistochemistry.
- Immune responses, specifically CD8+ T cell populations, were analyzed using flow cytometry.
Main Results:
- SARS-CoV-2/BMA8 induced lower pathogenicity and inflammation in C57BL/6N mice compared to BALB/c mice.
- The H-2K(d) haplotype in BALB/c mice correlated with more severe pathogenicity, while H-2K(b) blockade in C57BL/6N mice mimicked this effect.
- H-2K(b) inhibition exacerbated cytokine/chemokine expression and accelerated CD8+ T cell reduction post-infection.
Conclusions:
- Host Major Histocompatibility Complex (MHC) molecules are crucial determinants of SARS-CoV-2/BMA8 infection pathogenicity.
- These findings offer deeper insights into SARS-CoV-2 pathogenesis and inform strategies for viral control.
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