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Apoptosis and pyroptosis in the nasal mucosa of Syrian hamster during SARS-CoV-2 infection and reinfection

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Abstract

In SARS-CoV-2 infection, it has been observed that viral replication lasts longer in the nasal mucosa than in the lungs, despite the presence of a high viral load at both sites. In hamsters, we found that the nasal mucosa exhibited a mild inflammatory response and minimal pathological injuries, whereas the lungs displayed a significant inflammatory response and severe injuries. The underlying cellular events may be induced by viral infection in three types of cell death: apoptosis, pyroptosis, and necroptosis. Our findings indicate that apoptosis was consistently activated during infection in the nasal mucosa, and the levels of apoptosis were consistent with the viral load. On the other hand, pyroptosis and a few instances of necroptosis were observed only on 7 dpi in the nasal mucosa. In the lungs, however, both pyroptosis and apoptosis were prominently activated on 3 dpi, with lower levels of apoptosis compared to the nasal mucosa. Interestingly, in reinfection, obvious viral load and apoptosis in the nasal mucosa were detected on 3 dpi, while no other forms of cell death were detected. We noted that the inflammatory reactions and pathological injuries in the nasal mucosa were milder, indicating that apoptosis may play a role in promoting lower inflammatory reactions and milder pathological injuries and contribute to the generation of long-term viral replication in the nasal mucosa. Our study provides valuable insights into the differences in cellular mechanisms during SARS-CoV-2 infection and highlights the potential significance of apoptosis regulation in the respiratory mucosa for controlling viral replication.

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Data availability

All the data generated or analyzed during this study are included in this published article, and the additional files are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the Kunming National High-level Biosafety Primate Research Center for its support.

Funding

This research was funded by CAMS Innovation Fund for Medical Sciences (2022-I2M-CoV19-007), the Yunnan Applied Basic Research Projects (202301AS070066, 202201AT070239), the Yunnan Provincial Science and Technology Department (202102AA310043), and the Technology talent and platform plan of Yunnan Provincial Science and Technology Department (202305AD160006, 2022SCP010).

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Author notes

  1. Heng Li, Xin Zhao, Xinglong Zhang, and Huiwen Zheng have contributed equally to this work.

Authors and Affiliations

  1. Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, 650118, China

    Heng Li, Xin Zhao, Xinglong Zhang, Huiwen Zheng, Yibin Wang, Jinghan Hou, Jing Li, Yurong Zhao, Shasha Peng, Yingyan Li, Xin Zhang, Yifan Zhang, Jinling Yang, Zihan Zhang, Haijing Shi & Longding Liu

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  1. Heng Li
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  2. Xin Zhao
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Contributions

LD.L promote and host the studies. LD.L and H.L designed the studies, analyzed the data and wrote the manuscript. H.L and X.Z prepared and analyzed the data in the manuscript. H.L, X.Z, XL.Z and HW.Z performed the experiments. YB.W and J.L performed the Western blot, JH.H performed the statistical analysis, JL.Y and HT.L participated in Histopathology experiments. All the authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Longding Liu.

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Li, H., Zhao, X., Zhang, X. et al. Apoptosis and pyroptosis in the nasal mucosa of Syrian hamster during SARS-CoV-2 infection and reinfection. Apoptosis (2024). https://doi.org/10.1007/s10495-024-01940-x

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