Alayli Farah, Scholle Frank
Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
Virology. 2016 Sep;496:227-236. doi: 10.1016/j.virol.2016.06.008. Epub 2016 Jun 24.
Dengue virus (DV) has become the most prevalent arthropod borne virus due to globalization and climate change. It targets dendritic cells during infection and leads to production of pro-inflammatory cytokines and chemokines. Several DV non-structural proteins (NS) modulate activation of human dendritic cells. We investigated the effect of DV NS1 on human monocyte-derived dendritic cells (mo-DCs) during dengue infection. NS1 is secreted into the serum of infected individuals where it interacts with various immune mediators and cell types. We purified secreted DV1 NS1 from supernatants of 293T cells that over-express the protein. Upon incubation with mo-DCs, we observed NS1 uptake and enhancement of early DV1 replication. As a consequence, mo-DCs that were pre-exposed to NS1 produced more pro-inflammatory cytokines in response to subsequent DV infection compared to DCs exposed to heat-inactivated NS1 (HNS1). Therefore the presence of exogenous NS1 is able to modulate dengue infection in mo-DCs.
由于全球化和气候变化,登革热病毒(DV)已成为最普遍的节肢动物传播病毒。它在感染期间靶向树突状细胞,并导致促炎细胞因子和趋化因子的产生。几种登革热病毒非结构蛋白(NS)调节人类树突状细胞的激活。我们研究了登革热感染期间DV NS1对人单核细胞衍生树突状细胞(mo-DC)的影响。NS1分泌到受感染个体的血清中,在那里它与各种免疫介质和细胞类型相互作用。我们从过表达该蛋白的293T细胞的上清液中纯化了分泌的DV1 NS1。与mo-DC孵育后,我们观察到NS1的摄取和早期DV1复制的增强。因此,与暴露于热灭活NS1(HNS1)的树突状细胞相比,预先暴露于NS1的mo-DC在随后的DV感染时产生更多的促炎细胞因子。因此,外源性NS1的存在能够调节mo-DC中的登革热感染。