An inhibitor of leukotriene-A4 hydrolase from bat salivary glands facilitates virus infection

Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2110647119. doi: 10.1073/pnas.2110647119. Epub 2022 Mar 1.

Abstract

SignificanceAn immunosuppressant protein (MTX), which facilitates virus infection by inhibiting leukotriene A4 hydrolase (LTA4H) to produce the lipid chemoattractant leukotriene B4 (LTB4), 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 LTA4H 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 LTA4H, without affecting its antiinflammatory activity, MTX might be a potential candidate for the development of antiinflammatory drugs by targeting the LTA4-LTA4H-LTB4 inflammatory axis.

Keywords: Myotis pilosus; immunosuppressive; salivary gland; toxin; virus transmission.

MeSH terms

  • 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*

Substances

  • Enzyme Inhibitors
  • Leukotriene A4
  • Salivary Proteins and Peptides
  • Epoxide Hydrolases
  • leukotriene A4 hydrolase