Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection.

Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection.
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DOI:
10.1371/journal.pntd.0004941
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发表时间:
2016-09
影响因子:
3.8
通讯作者:
Colpitts TM
Colpitts TM
中科院分区:
医学2区
文献类型:
--
作者:
Conway MJ;Londono-Renteria B;Troupin A;Watson AM;Klimstra WB;Fikrig E;Colpitts TM

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埃及伊蚊是包括1 - 4型登革病毒(DENV)在内的几种医学相关虫媒病毒的主要传播媒介。埃及伊蚊在刺探和吸食过程中将感染病毒的唾液注入宿主皮肤从而传播登革病毒。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,包括促进吸血。此前,我们发现埃及伊蚊的唾液腺提取物(SGEs)增强了登革病毒向引流淋巴结的传播。相比之下,高效液相色谱分级分离显示一些唾液腺提取物成分抑制感染。在此,我们表明D7蛋白在对登革病毒感染有抑制作用的高效液相色谱组分中富集,并且重组D7蛋白在体外和体内都能抑制登革病毒感染。此外,结合试验表明D7蛋白能够与登革病毒粒子以及重组登革病毒包膜蛋白直接相互作用。这些数据揭示了D7蛋白的一种新作用,即通过与病毒粒子直接相互作用抑制虫媒病毒向脊椎动物的传播。 登革病毒(DENV)在吸血过程中由埃及伊蚊传播给人类。在吸血过程中,登革病毒和唾液蛋白质被注入人类皮肤。D7蛋白是埃及伊蚊唾液中普遍存在且具有免疫原性的蛋白质,通过清除生物胺辅助吸血过程。先前的数据表明,针对库蚊属D7蛋白的抗体可增加西尼罗河病毒感染。我们假设D7蛋白可能也具有抗病毒活性。在此,我们表明重组埃及伊蚊D7蛋白在体外和体内都能抑制登革病毒感染,并且D7能够结合登革病毒粒子。
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. Dengue virus (DENV) is transmitted to humans by Aedes aegypti during the blood feeding process. During blood feeding, DENV and saliva proteins are inoculated into human skin. D7 proteins are prevalent and immunogenic proteins present in Ae. aegypti saliva, and assist the blood feeding process by scavenging biogenic amines. Previous data suggests that antibodies against D7 protein from Culex spp. can increase West Nile virus infection. We hypothesized that D7 proteins may also have antiviral activity. Here, we show that recombinant Ae. aegypti D7 protein can inhibit DENV infection in vitro and in vivo, and that D7 can bind to DENV virions.
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