An inhibitor of leukotriene-A 4 hydrolase from bat salivary glands facilitates virus infection

Author:

Fang Mingqian1,Tang Xiaopeng1ORCID,Zhang Juan2,Liao Zhiyi13ORCID,Wang Gan145ORCID,Cheng Ruomei13ORCID,Zhang Zhiye145ORCID,Zhao Hongwen2,Wang Jing6,Tan Zhaoxia2,Kamau Peter Muiruri135ORCID,Lu Qiumin1345ORCID,Liu Qi3,Deng Guohong2,Lai Ren1345ORCID

Affiliation:

1. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Kunming 650107, Yunnan, China

2. Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China

3. Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China

4. Institutes for Drug Discovery and Development, Chinese Academy of Sciences, Shanghai 201203, China

5. Sino-African Joint Research Center, Chinese Academy of Sciences, Wuhan, Hubei 430074, China

6. Department of Laboratory Diagnosis, Chongqing Public Health Medical Center, Public Health Hospital of Southwest University, Shapingba District, Chongqing 400038, China

Abstract

Significance An immunosuppressant protein (MTX), which facilitates virus infection by inhibiting leukotriene A 4 hydrolase (LTA 4 H) to produce the lipid chemoattractant leukotriene B 4 (LTB 4 ), was identified and characterized from the submandibular salivary glands of the bat Myotis pilosus . To the best of our knowledge, this is a report of an endogenous LTA 4 H inhibitor in animals. MTX was highly concentrated in the bat salivary glands, suggesting a mechanism for the generation of immunological privilege and immune tolerance and providing evidence of viral shedding through oral secretions. Moreover, given that the immunosuppressant MTX selectively inhibited the proinflammatory activity of LTA 4 H, without affecting its antiinflammatory activity, MTX might be a potential candidate for the development of antiinflammatory drugs by targeting the LTA 4 -LTA 4 H-LTB 4 inflammatory axis.

Funder

The Ministry of Science and Technology of China

National Science Foundation of China

The Chinese Academy of Sciences

K. C. Wong Education Foundation

Science and Technology Department of Yunnan Province

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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