Effects of Manipulating Fibroblast Growth Factor Expression on Sindbis Virus Replication In Vitro and in Aedes aegypti Mosquitoes.

Effects of Manipulating Fibroblast Growth Factor Expression on Sindbis Virus Replication In Vitro and in Aedes aegypti Mosquitoes.
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DOI:
10.3390/v12090943
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发表时间:
2020-08-26
期刊:
Viruses
影响因子:
--
通讯作者:
Passarelli AL
Passarelli AL
中科院分区:
其他
文献类型:
--
作者:
Wu W;Simmons CA;Moffitt J;Clem RJ;Passarelli AL

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成纤维细胞生长因子(FGF)在脊椎动物和无脊椎动物中是保守的,并且在细胞增殖、细胞分化、组织修复和胚胎发育中起作用。病毒成纤维细胞生长因子(vFGF)同源物由杆状病毒编码,杆状病毒是一组昆虫病毒,其通过刺激基底层重塑参与杆状病毒从昆虫中肠的逃逸。这使我们研究细胞FGF是否参与虫媒病毒从蚊子中肠的逃逸。在这项研究中,操纵FGF表达对辛德毕斯病毒(SINV)复制和逃逸的蚊子载体埃及伊蚊中肠的影响进行了检查。RNAi介导的Ae.埃及伊蚊FGF(AeFGF)或FGF受体(AeFGFR)表达降低了Ae.埃及蚊子。然而,使用重组SINV构建体的杆状病毒vFGF的过表达对这些病毒在培养的蚊子或脊椎动物细胞中或在经口感染的Ae中的复制没有影响。埃及蚊子。我们的结论是,减少FGF信号降低了SINV在蚊子中复制的能力,但vFGF的过表达没有影响,可能是因为内源性FGF水平已经足以进行最佳病毒复制。这些结果支持这一假设,即FGF信号,可能通过诱导中肠基膜的重塑,参与虫媒病毒中肠逃逸后,病毒收购的血餐。
Fibroblast growth factors (FGFs) are conserved among vertebrate and invertebrate animals and function in cell proliferation, cell differentiation, tissue repair, and embryonic development. A viral fibroblast growth factor (vFGF) homolog encoded by baculoviruses, a group of insect viruses, is involved in escape of baculoviruses from the insect midgut by stimulating basal lamina remodeling. This led us to investigate whether cellular FGF is involved in the escape of an arbovirus from mosquito midgut. In this study, the effects of manipulating FGF expression on Sindbis virus (SINV) replication and escape from the midgut of the mosquito vector Aedes aegypti were examined. RNAi-mediated silencing of either Ae. aegypti FGF (AeFGF) or FGF receptor (AeFGFR) expression reduced SINV replication following oral infection of Ae. aegypti mosquitoes. However, overexpression of baculovirus vFGF using recombinant SINV constructs had no effect on replication of these viruses in cultured mosquito or vertebrate cells, or in orally infected Ae. aegypti mosquitoes. We conclude that reducing FGF signaling decreases the ability of SINV to replicate in mosquitoes, but that overexpression of vFGF has no effect, possibly because endogenous FGF levels are already sufficient for optimal virus replication. These results support the hypothesis that FGF signaling, possibly by inducing remodeling of midgut basal lamina, is involved in arbovirus midgut escape following virus acquisition from a blood meal.
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