Mosquito Saliva Serine Protease Enhances Dissemination of Dengue Virus into the Mammalian Host

文献类型： 外文期刊

第一作者： Conway, Michael J.

作者： Conway, Michael J.;Colpitts, Tonya M.;Dragovic, Srdjan M.;Li, Zhiyong;Wang, Penghua;Feitosa, Fabiana;Shepherd, Denueve T.;Fikrig, Erol;Conway, Michael J.;Watson, Alan M.;Ryman, Kate D.;Klimstra, William B.;Watson, Alan M.;Ryman, Kate D.;Klimstra, William B.;Conway, Michael J.;Anderson, John F.;Li, Zhiyong;Feitosa, Fabiana;Fikrig, Erol

作者机构：

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：5.103； 五年影响因子：5.078 ）

ISSN： 0022-538X

年卷期： 2014 年 88 卷 1 期

页码：

收录情况： SCI

摘要： Dengue virus (DENV), a flavivirus of global importance, is transmitted to humans by mosquitoes. In this study, we developed in vitro and in vivo models of saliva-mediated enhancement of DENV infectivity. Serine protease activity in Aedes aegypti saliva augmented virus infectivity in vitro by proteolyzing extracellular matrix proteins, thereby increasing viral attachment to heparan sulfate proteoglycans and inducing cell migration. A serine protease inhibitor reduced saliva-mediated enhancement of DENV in vitro and in vivo, marked by a 100-fold reduction in DENV load in murine lymph nodes. A saliva-mediated infectivity enhancement screen of fractionated salivary gland extracts identified serine protease CLIPA3 as a putative cofactor, and short interfering RNA knockdown of CLIPA3 in mosquitoes demonstrated its role in influencing DENV infectivity. Molecules in mosquito saliva that facilitate viral infectivity in the vertebrate host provide novel targets that may aid in the prevention of disease.

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