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MHC class I links with severe pathogenicity in C57BL/6N mice infected with SARS-CoV-2/BMA8.
Qin, Tian; Shen, Beilei; Li, Entao; Jin, Song; Luo, Rongbo; Zhang, Yiming; Qi, Jing; Deng, Xiuwen; Shi, Zhuangzhuang; Wang, Tiecheng; Zhou, Yifa; Gao, Yuwei.
  • Qin T; School of life sciences, Northeast Normal University, Changchun, 130024, China.
  • Shen B; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China.
  • Li E; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China.
  • Jin S; Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China.
  • Luo R; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China.
  • Zhang Y; College of life sciences, Shandong Normal University, Jinan, 250014, China.
  • Qi J; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China.
  • Deng X; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China.
  • Shi Z; School of life sciences, Northeast Normal University, Changchun, 130024, China.
  • Wang T; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China.
  • Zhou Y; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China.
  • Gao Y; College of Integrated Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China.
Virol J ; 20(1): 75, 2023 04 20.
Article in English | MEDLINE | ID: covidwho-2302137
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-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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study Limits: Animals Language: English Journal: Virol J Journal subject: Virology Year: 2023 Document Type: Article Affiliation country: S12985-023-02031-0

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study Limits: Animals Language: English Journal: Virol J Journal subject: Virology Year: 2023 Document Type: Article Affiliation country: S12985-023-02031-0