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  3. Modulating apoptosis as a novel therapeutic strategy against Respiratory Syncytial Virus infection: insights from Rotenone

Modulating apoptosis as a novel therapeutic strategy against Respiratory Syncytial Virus infection: insights from Rotenone

  • Antiviral Res. 2024 Sep 17:231:106007. doi: 10.1016/j.antiviral.2024.106007.
Ke Zhang 1,  Xiao-Meng Yang 2,  Haoran Sun 3,  Zhong-Shan Cheng 4,  Jianqing Peng 5,  Minjun Dong 6,  Fang Chen 7,  Huyan Shen 7,  Pingping Zhang 7,  Jin-Fu Li 7,  Yong Zhang 8,  Chunlai Jiang 8,  Jiandong Huang 9,  Jasper Fuk-Woo Chan 10,  Shuofeng Yuan 11,  Yu-Si Luo 12,  Xiang-Chun Shen 13
Affiliations

Affiliations

  • 1 Guizhou Key Laboratory of Microbio and Infectious Disease Prevention & Control, Virology Institute, Department of Human Parasitology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 561113, China; The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, 561113, China.
  • 2 Guizhou Key Laboratory of Microbio and Infectious Disease Prevention & Control, Virology Institute, Department of Human Parasitology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 561113, China; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 3 Chinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518000, China; Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 518000, China.
  • 4 Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, 38105, United States.
  • 5 State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, 561113, China.
  • 6 Department of Surgical Oncology, Sir Run Run Shaw Hospital Affiliated to Zhejiang University, School of Medicine, Hangzhou, 310000, China.
  • 7 Guizhou Key Laboratory of Microbio and Infectious Disease Prevention & Control, Virology Institute, Department of Human Parasitology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 561113, China.
  • 8 National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130000, China.
  • 9 Chinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518000, China.
  • 10 Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 518000, China.
  • 11 Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 518000, China. Electronic address: yuansf@hku.hk.
  • 12 Department of Emergency ICU, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China; Department of Emergency, Liupanshui Hospital of the Affiliated Hospital of Guizhou Medical University, Liupanshui, 553000, China. Electronic address: roseluogy@outlook.com.
  • 13 The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, 561113, China. Electronic address: shenxiangchun@126.com.
PMID: 39299548 DOI: 10.1016/j.antiviral.2024.106007
Abstract

Respiratory syncytial virus (RSV) is a significant cause of acute lower respiratory tract infections, particularly in vulnerable populations such as neonates, infants, young children, and the elderly. Among infants, RSV is the primary cause of bronchiolitis and pneumonia, contributing to a notable proportion of child mortality under the age of 5. In this study, we focused on investigating the pathogenicity of a lethal RSV strain, GZ08-18, as a model for understanding mechanisms of hypervirulent RSV. Our findings indicate that the heightened pathogenicity of GZ08-18 stems from compromised activation of intrinsic Apoptosis, as evidenced by aberration of mitochondrial membrane depolarization in host cells. We thus hypothesized that enhancing intrinsic Apoptosis could potentially attenuate the virulence of RSV strains and explored the effects of Rotenone, a natural compound known to stimulate the intrinsic Apoptosis pathway, on inhibiting RSV Infection. Our results demonstrate that Rotenone treatment significantly improved mouse survival rates and mitigated lung pathology following GZ08-18 Infection. These findings suggest that modulating the suppressed Apoptosis induced by RSV Infection represents a promising avenue for Antiviral intervention strategies.

Keywords

Antivirals; Intrinsic apoptosis; Lethal RSV strain; Respiratory syncytial virus; Rotenone.

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