Institute of Virology and Immunology (IVI), Bern, Switzerland.
Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Front Cell Infect Microbiol. 2019 Jan 28;9:5. doi: 10.3389/fcimb.2019.00005. eCollection 2019.
Several mosquito-borne Flaviviruses such as Japanese encephalitis virus (JEV), West Nile virus (WNV), Dengue Virus (DENV), and Zika virus (ZIKV) can cause severe clinical disease. Being zoonotic, Flaviviruses infect a wide variety of terrestrial vertebrates, which dependent of the virus-host interactions, can enhance ongoing epidemics and maintain the virus in the environment for prolonged periods. Targeted species can vary from amphibians, birds to various mammals, dependent on the virus. For many mosquito-borne flaviviruses the spectrum of targeted species is incompletely understood, in particular with respect to their contribution to the maintenance of virus in certain geographical regions. Furthermore, little is known about virus and host factors contributing to species tropism. The present study utilized human and porcine monocyte-derived dendritic cells (MoDC) as a cell culture model to better understand Flavivirus species tropism and innate immune responses. MoDC were selected based on their presence in the skin and their role as an early target cell for several Flaviviruses and their role as immune sentinels. While differences in viral infectivity and replication were minor when comparing porcine with human MoDC for some of the tested Flaviviruses, a particularly strong replication in human MoDC was found with USUV, while JEV appeared to have a stronger tropism for porcine MoDC. With respect to innate immune responses we found high induction of TNF and IFN-β in both human and porcine MoDC after infection with JEV, WNV, and USUV, but not with DENV, ZIKV, and Wesselsbron virus. Spondweni virus induced these cytokine responses only in porcine MoDC. Overall, innate immune responses correlated with early infectivity and cytokine production. In conclusion, we demonstrate Flavivirus-dependent differences in the interaction with MoDC. These may play a role in pathogenesis but appear to only partially reflect the expected species tropism.
几种蚊媒黄病毒，如日本脑炎病毒（JEV）、西尼罗河病毒（WNV）、登革热病毒（DENV）和寨卡病毒（ZIKV），可导致严重的临床疾病。黄病毒具有亲动物性，可感染多种陆生脊椎动物，这取决于病毒-宿主相互作用，可增强正在发生的流行，并使病毒在环境中长时间存在。目标物种可从两栖动物、鸟类到各种哺乳动物不等，这取决于病毒。对于许多蚊媒黄病毒来说，目标物种的范围并不完全清楚，特别是关于它们对特定地理区域病毒维持的贡献。此外，关于导致物种嗜性的病毒和宿主因素知之甚少。本研究利用人源和猪源单核细胞衍生的树突状细胞（MoDC）作为细胞培养模型，以更好地理解黄病毒的物种嗜性和先天免疫反应。选择 MoDC 是基于它们存在于皮肤中，以及它们作为几种黄病毒的早期靶细胞和免疫哨兵的作用。虽然在比较一些测试的黄病毒时，猪源和人源 MoDC 的病毒感染性和复制差异较小，但 USUV 在人源 MoDC 中的复制特别强，而 JEV 似乎对猪源 MoDC 具有更强的嗜性。就先天免疫反应而言，我们发现 JEV、WNV 和 USUV 感染后，人源和猪源 MoDC 中 TNF 和 IFN-β 的诱导均很高，但 DENV、ZIKV 和 Wesselsbron 病毒则不然。Spondweni 病毒仅在猪源 MoDC 中诱导这些细胞因子反应。总的来说，先天免疫反应与早期感染性和细胞因子产生相关。总之，我们证明了黄病毒与 MoDC 相互作用的依赖性差异。这些差异可能在发病机制中起作用，但似乎仅部分反映预期的物种嗜性。
