Conway Michael J, Londono-Renteria Berlin, Troupin Andrea, Watson Alan M, Klimstra William B, Fikrig Erol, Colpitts Tonya M
Foundational Sciences, Central Michigan University College of Medicine, Mt. Pleasant, Michigan, United States of America.
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America.
PLoS Negl Trop Dis. 2016 Sep 15;10(9):e0004941. doi: 10.1371/journal.pntd.0004941. eCollection 2016 Sep.
Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions.
埃及伊蚊是包括1 - 4型登革病毒在内的几种医学相关虫媒病毒的主要传播媒介。埃及伊蚊在刺叮和取食过程中,通过将感染病毒的唾液接种到宿主皮肤中来传播登革病毒。埃及伊蚊的唾液含有一百多种独特的蛋白质,这些蛋白质具有多种功能,包括促进血液摄取。此前,我们发现埃及伊蚊唾液腺提取物(SGEs)可增强登革病毒向引流淋巴结的扩散。相比之下,高效液相色谱(HPLC)分级分离显示,一些SGE成分可抑制感染。在此,我们表明D7蛋白在对登革病毒感染具有抑制作用的HPLC级分中富集,并且重组D7蛋白在体外和体内均可抑制登革病毒感染。此外,结合试验表明D7蛋白可直接与登革病毒粒子和重组登革病毒包膜蛋白相互作用。这些数据揭示了D7蛋白的一种新作用,即通过与病毒粒子的直接相互作用来抑制虫媒病毒向脊椎动物的传播。