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

Resumo: 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.

Palavras-Chave: Yellow fever mosquito; West nile virus; Langerhans cell migration; Borne Encephalitis virus; Aedes aegypti; Heparan sulfate; Immune response; Arbovirus transmission; Infection; Disease

Imprenta: Journal of Virology, v. 88, n. 1, p. 164-175, 2014

Identificador do objeto digital: 10.1128/JVI.02235-13

Descritores: Aedes aegypti - Biochemistry ; Aedes aegypti - Cell ; Aedes aegypti - Immune response ; Aedes aegypti - Molecular structure ; Aedes aegypti - RNA ; Aedes aegypti - Immunology ; Aedes aegypti - Viral infections ; Aedes aegypti - Virus ; Aedes aegypti - Molecular screening ; Aedes aegypti - Public health

Data de publicação: 2014

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