MHC class I links with severe pathogenicity in C57BL/6N mice infected with SARS-CoV-2/BMA8

Tian Qin; Beilei Shen; Entao Li; Song Jin; Rongbo Luo; Yiming Zhang; Jing Qi; Xiuwen Deng; Zhuangzhuang Shi; Tiecheng Wang; Yifa Zhou; Yuwei Gao

doi:10.1186/s12985-023-02031-0

MHC class I links with severe pathogenicity in C57BL/6N mice infected with SARS-CoV-2/BMA8

Virol J. 2023 Apr 20;20(1):75. doi: 10.1186/s12985-023-02031-0.

Authors

Tian Qin^{1

2}, Beilei Shen², Entao Li³, Song Jin^{2

4}, Rongbo Luo², Yiming Zhang², Jing Qi^{1

2}, Xiuwen Deng^{2

5}, Zhuangzhuang Shi^{2

6}, Tiecheng Wang², Yifa Zhou⁷, Yuwei Gao⁸

Affiliations

¹ School of life sciences, Northeast Normal University, Changchun, 130024, China.
² Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China.
³ Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China.
⁴ College of life sciences, Shandong Normal University, Jinan, 250014, China.
⁵ College of Integrated Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China.
⁶ College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130033, China.
⁷ School of life sciences, Northeast Normal University, Changchun, 130024, China. zhouyf383@nenu.edu.cn.
⁸ Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China. gaoyuwei@gmail.com.

Abstract

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-2K^d showed more severe pathogenicity after infection with BMA8 strain, while blockade of H-2K^b in C57BL/6N mice was also able to cause this phenomenon. Furthermore, H-2K^b 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.

Keywords: CD8+ T cells; Immune response; MHC class I; Pathogenicity severity; SARS-CoV-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes
COVID-19* / pathology
Disease Models, Animal
Inflammation
Lung / pathology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
SARS-CoV-2*
Virulence