tetano
Editor, Senior Moderator
Virol J
. 2023 Apr 20;20(1):75.
doi: 10.1186/s12985-023-02031-0.
MHC class I links with severe pathogenicity in C57BL/6N mice infected with SARS-CoV-2/BMA8
Tian Qin[SUP] 1 2 [/SUP], Beilei Shen[SUP] 2 [/SUP], Entao Li[SUP] 3 [/SUP], Song Jin[SUP] 2 4 [/SUP], Rongbo Luo[SUP] 2 [/SUP], Yiming Zhang[SUP] 2 [/SUP], Jing Qi[SUP] 1 2 [/SUP], Xiuwen Deng[SUP] 2 5 [/SUP], Zhuangzhuang Shi[SUP] 2 6 [/SUP], Tiecheng Wang[SUP] 2 [/SUP], Yifa Zhou[SUP] 7 [/SUP], Yuwei Gao[SUP] 8 [/SUP]
Affiliations
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[SUP]+[/SUP] 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[SUP]d[/SUP] showed more severe pathogenicity after infection with BMA8 strain, while blockade of H-2K[SUP]b[/SUP] in C57BL/6N mice was also able to cause this phenomenon. Furthermore, H-2K[SUP]b[/SUP] inhibition increased the expression of cytokines/chemokines and accelerated the decrease of CD8[SUP]+[/SUP] 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.
. 2023 Apr 20;20(1):75.
doi: 10.1186/s12985-023-02031-0.
MHC class I links with severe pathogenicity in C57BL/6N mice infected with SARS-CoV-2/BMA8
Tian Qin[SUP] 1 2 [/SUP], Beilei Shen[SUP] 2 [/SUP], Entao Li[SUP] 3 [/SUP], Song Jin[SUP] 2 4 [/SUP], Rongbo Luo[SUP] 2 [/SUP], Yiming Zhang[SUP] 2 [/SUP], Jing Qi[SUP] 1 2 [/SUP], Xiuwen Deng[SUP] 2 5 [/SUP], Zhuangzhuang Shi[SUP] 2 6 [/SUP], Tiecheng Wang[SUP] 2 [/SUP], Yifa Zhou[SUP] 7 [/SUP], Yuwei Gao[SUP] 8 [/SUP]
Affiliations
- PMID: 37081549
- DOI: 10.1186/s12985-023-02031-0
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[SUP]+[/SUP] 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[SUP]d[/SUP] showed more severe pathogenicity after infection with BMA8 strain, while blockade of H-2K[SUP]b[/SUP] in C57BL/6N mice was also able to cause this phenomenon. Furthermore, H-2K[SUP]b[/SUP] inhibition increased the expression of cytokines/chemokines and accelerated the decrease of CD8[SUP]+[/SUP] 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.