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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2022-03, Vol.119 (10), p.e2110647119
• Main Authors: Fang, Mingqian, Tang, Xiaopeng, Zhang, Juan, Liao, Zhiyi, Wang, Gan, Cheng, Ruomei, Zhang, Zhiye, Zhao, Hongwen, Wang, Jing, Tan, Zhaoxia, Kamau, Peter Muiruri, Lu, Qiumin, Liu, Qi, Deng, Guohong, Lai, Ren
• Format: Article
• Language: English
• Subjects: Animals; Chiroptera; Enzyme Inhibitors - metabolism; Epoxide Hydrolases - antagonists & inhibitors; Epoxide Hydrolases - metabolism; Influenza A Virus, H1N1 Subtype - metabolism; Leukotriene A4 - metabolism; Mice; Orthomyxoviridae Infections - enzymology; Salivary Glands - enzymology; Salivary Glands - virology; Salivary Proteins and Peptides - metabolism; Virus Diseases
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2110647119

SignificanceAn immunosuppressant protein (MTX), which facilitates virus infection by inhibiting leukotriene A hydrolase (LTA H) to produce the lipid chemoattractant leukotriene B (LTB ), was identified and characterized from the submandibular salivary glands of the bat . To the best of our knowledge, this is a report of an endogenous LTA 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 H, without affecting its antiinflammatory activity, MTX might be a potential candidate for the development of antiinflammatory drugs by targeting the LTA -LTA H-LTB inflammatory axis.