2. Academic Validation
  3. 25-Hydroxycholesterol inhibits Hantavirus infection by reprogramming cholesterol metabolism

25-Hydroxycholesterol inhibits Hantavirus infection by reprogramming cholesterol metabolism

  • Free Radic Biol Med. 2024 Aug 28:224:232-245. doi: 10.1016/j.freeradbiomed.2024.08.029.
Yamei Dang 1,  Yuan Wang 1,  Jing Wei 2,  Hui Zhang 1,  Qiqi Yang 1,  Bin Wang 3,  Jia Li 4,  Chuantao Ye 5,  Yang Chen 1,  Peijun Han 6,  Xiaolei Jin 7,  Jia Wang 7,  Xiaohui Bao 7,  He Liu 1,  Hongwei Ma 1,  Liang Zhang 1,  Linfeng Cheng 1,  Yangchao Dong 1,  Yinlan Bai 1,  Yinghui Li 1,  Yingfeng Lei 8,  Zhikai Xu 9,  Fanglin Zhang 10,  Wei Ye 11
Affiliations

Affiliations

  • 1 Department of Microbiology, School of Preclinical Medicine, Air Force Medical University: Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • 2 Department of Microbiology, School of Preclinical Medicine, Air Force Medical University: Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; Center for Disease Control and Prevention of Shaanxi Province, Xi'an, Shaanxi, China.
  • 3 Center of Clinical Aerospace Medicine, School of Aerospace Medicine, Air Force Medical University: Fourth Military Medical University, Xi'an, China.
  • 4 Department of Neurology, Xi'an International Medical Center Hospital, Xi'an, Shaanxi, 710100, China.
  • 5 Department of Infectious Diseases, Tangdu Hospital, Air Force Medical University: Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • 6 Department of Aerospace Hygiene, School of Aerospace Medicine, Air Force Medical University: Fourth Military Medical University, Xi'an, China.
  • 7 Cadet Brigade, School of Preclinical Medicine, Air Force Medical University: Fourth Military Medical University, Xi'an, 710032, China.
  • 8 Department of Microbiology, School of Preclinical Medicine, Air Force Medical University: Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. Electronic address: yflei@fmmu.edu.cn.
  • 9 Department of Microbiology, School of Preclinical Medicine, Air Force Medical University: Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. Electronic address: zhikaixu@fmmu.edu.cn.
  • 10 Department of Microbiology, School of Preclinical Medicine, Air Force Medical University: Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. Electronic address: flzhang@fmmu.edu.cn.
  • 11 Department of Microbiology, School of Preclinical Medicine, Air Force Medical University: Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. Electronic address: virologyyw@fmmu.edu.cn.
PMID: 39209137 DOI: 10.1016/j.freeradbiomed.2024.08.029
Abstract

Hantavirus causes two types of acute diseases: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. It is a major health concern due to its high mortality and lack of effective treatment. Type I interferon treatment has been suggested to be effective against hantavirus when treated in advance. Interferons induce multiple interferon-stimulated genes (ISGs), whose products are highly effective at resisting and controlling viruses. A product of ISGs, the enzyme Cholesterol 25-hydroxylase (CH25H), catalyzes the oxidation of Cholesterol to 25-hydroxycholesterol (25HC). 25HC can inhibit multiple enveloped-virus infections, but the mechanism is largely unknown, and whether 25HC plays an important role in regulating hantavirus remains unexplored. In this study, we show that Hantaan virus (HTNV), the prototype hantavirus, induced CH25H gene in infected cells. Overexpression of CH25H and treatment with 25HC, inhibited HTNV Infection, possibly by lowering 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase, HMGCR), which inhibits Cholesterol biosynthesis. In addition, cholesterol-lowering drugs such as HMGCR-targeting statins have potent hantavirus inhibitory effects. Our results indicate that 25HC and some statins are potential Antiviral agents effective against hantavirus infections. This study provides evidence that targeting Cholesterol metabolism is promising in developing specific hantavirus antivirals and indicates the possibility of repurposing FDA-approved cholesterol-lowering drug, statins for treating hantavirus Infection.

Keywords

25-hydroxycholesterol; 3-hydroxy-3-methyl-glutaryl coenzyme a reductase regulation; Cholesterol 25 -hydroxylase; Hantavirus; Hemorrhagic fever with renal syndrome; Statins.

Figures
Products