Evasins: Tick Salivary Proteins that Inhibit Mammalian Chemokines. Issue 2 (February 2020)

• Record Type: Journal Article
• Authors: Bhusal, Ram Prasad; Eaton, James R.O.; Chowdhury, Sayeeda T.; Power, Christine A.; Proudfoot, Amanda E.I.; Stone, Martin J.; Bhattacharya, Shoumo
• Is Part Of: Trends in biochemical sciences. Volume 45:Issue 2(2020)
• Page Start: 108
• Page End: 122
• Publication Date: 2020-02
• Subjects: Evasin -- chemokine -- binding protein -- protein family -- anti-inflammatory; Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2019.10.003
• Languages: English
• ISSNs: 0968-0004

Abstract

Abstract : Ticks are hematophagous arachnids that parasitize mammals and other hosts, feeding on their blood. Ticks secrete numerous salivary factors that enhance host blood flow or suppress the host inflammatory response. The recruitment of leukocytes, a hallmark of inflammation, is regulated by chemokines, which activate chemokine receptors on the leukocytes. Ticks target this process by secreting glycoproteins called Evasins, which bind to chemokines and prevent leukocyte recruitment. This review describes the recent discovery of numerous Evasins produced by ticks, their classification into two structural and functional classes, and the efficacy of Evasins in animal models of inflammatory diseases. The review also proposes a standard nomenclature system for Evasins and discusses the potential of repurposing or engineering Evasins as therapeutic anti-inflammatory agents. Highlights: Chemokines are mammalian proteins that are secreted at the sites of tissue insult and stimulate trafficking of leukocytes to the affected tissues, a key component of the inflammatory response. Evasins are tick salivary glycoproteins that bind to chemokines, thereby suppressing the host inflammatory response, an apparent mechanism to prolong the residence times of ticks on their hosts. Bioinformatics searches of salivary transcriptomic and genomic sequence databases and yeast surface display screening methods have enabled discovery of Evasins produced by numerous tick species spread across at least three genera. Two families of Evasins (Classes A and B) have been identified. Evasins from the two families have different 3D structures, different conserved sequence features (including patterns of disulfide bonds), and selectivity for different families of chemokines (CC and CXC, respectively). Evasins each bind to several (or many) chemokines but different Evasins have distinct selectivities for target chemokines. Structures, mutational experiments, and sequence comparisons are beginning to reveal the critical elements of Evasins for chemokine recognition. Evasins show efficacy in animal models of inflammatory diseases, suggesting that either natural Evasins or engineered variants have potential as therapeutic anti-inflammatory agents.