Chronobiology of neurotropic viruses: rhythmic viral entry and arrhythmic host clocks

  • Cell Discov. 2026 Feb 10;12(1):11. doi: 10.1038/s41421-026-00867-8.
Shaowei Zeng  1  2 ,  Qian Zhang  3  4 ,  Xue Yang  1  2 ,  Linyue Lv  1  2 ,  Yuelan Zhang  1  2 ,  Zhuyou Zhang  1  2 ,  Qinyang Wang  1  2 ,  Min-Hua Luo  5 ,  Martin Dorf  6 ,  Shitao Li  7 ,  Ling Zhao  8  9 ,  Bishi Fu  10  11
Affiliations
  • 1. Department of Rheumatology and Immunology, State Key Laboratory of Virology and Biosafety, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China.
  • 2. Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan, Hubei, China.
  • 3. Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China.
  • 4. School of Life Sciences, Yunnan University, Kunming, Yunnan, China.
  • 5. State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • 6. Department of Microbiology & Immunobiology, Harvard Medical School, Boston, MA, USA.
  • 7. Department of Microbiology and Immunology, Tulane University, New Orleans, LA, USA.
  • 8. State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China.
  • 9. Key Laboratory of Preventive Veterinary Medicine of Hubei Province, Huazhong Agricultural University, Wuhan, Hubei, China.
  • 10. Department of Rheumatology and Immunology, State Key Laboratory of Virology and Biosafety, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China. [email protected].
  • 11. Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan, Hubei, China. [email protected].
PMID: 41663379 DOI: 10.1038/s41421-026-00867-8
Abstract

Neurotropic viruses invade neural tissues, resulting in severe diseases such as poliomyelitis, rabies, herpesviral encephalitis, and viral meningitis. Given this neurotropism, we investigated whether the Infection of the host by these viruses is under circadian control. In this study, we found that the expression of most neurotropic virus receptors exhibits rhythmicity across cells, cerebral organoids, and animal models, with host cell susceptibility modulated by the circadian clock. We identified E2F8 as a clock-controlled gene that mediates the indirect regulation of the circadian clock on neurotropic viruses. Notably, E2F8 regulated the expression of core clock components by binding directly to the promoters of REV-ERBα and PER2, suggesting its role as a potential modulator of circadian rhythms. Additionally, we revealed a seldom-recognized viral strategy to accelerate viral replication in the host: rabies virus disrupts the host circadian clock system primarily through its glycoprotein hijacking the E3 ubiquitin Ligase HUWE1 to inhibit proteasomal degradation of REV-ERBα. These findings increase our understanding of the interactions between circadian systems and neurotropic viral dynamics and highlight the potential of chronotherapy for improved Antiviral treatments.

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