부산대학교 도서관

Bats are increasingly accepted as potential reservoirs of many viruses that cause zoonotic disease outbreaks through spillover to other animals and humans. However, our understanding of the factors that contribute to virus spillover from bats is very limited. Here, we identified and characterized an immunosuppressant pro- tein (MTX) that is highly concentrated in the submandibular salivary gland of the bat, Myotis pilosus. By selectively inhibiting the epoxide hydrolase function of leukotriene-A4 hydrolase (LTA4H) to inhibit LTA4 hydrolysis and the generation of leukotriene B4 (LTB4), a potent lipid chemoattractant for host defense against infection, MTX inhibited the antiviral responses of the host and facilitated viral infection. MTX had no effect on the aminopeptidase function of LTA4H and therefore did not impair the antiinflammatory function of LTA4H. MTX potently inhibited proinflammatory proteases (i.e., plasmin, trypsin, and elastase) to induce immune tolerance and maintain high stability. In mouse models, influenza A virus (IAV) H1N1 infection and pathogenicity were exacerbated by MTX but were reversed by interfering with the effects of MTX on LTA4H or exogenous LTB4 administration. This study provides deeper insight into immunologically privileged sites for microbial community residence in bats and supports the therapeutic potential of targeting MTX-LTA4H. [ABSTRACT FROM AUTHOR]