Abstract
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.
Highlights
Within the genus of Flavivirus more than 60 species are described, which are mostly transmitted by arthropods to vertebrates. 50% of these virus species are mosquito-born, 28% are transmitted by ticks, and for the rest the vector is unknown (Simmonds et al, 2017)
At 24 h pMoDC showed the highest susceptibility to Usutu virus (USUV) followed by Japanese encephalitis virus (JEV), West Nile virus (WNV) and Spondweni virus (SPOV), and the lowest infectivity was found with Dengue Virus (DENV)-3 and Zika virus (ZIKV) (Figure 1A)
With hMoDC, highest susceptibilities were found with USUV and SPOV, followed by JEV, WNV, DENV-3, ZIKV, and Wesselsbron virus (WESSV) (Figure 1C)
Summary
Within the genus of Flavivirus more than 60 species are described, which are mostly transmitted by arthropods to vertebrates. 50% of these virus species are mosquito-born, 28% are transmitted by ticks, and for the rest the vector is unknown (Simmonds et al, 2017). Within the genus of Flavivirus more than 60 species are described, which are mostly transmitted by arthropods to vertebrates. 50% of these virus species are mosquito-born, 28% are transmitted by ticks, and for the rest the vector is unknown (Simmonds et al, 2017). The recent identification of human cases of DENV after local transmission in different countries of Europe (France and Spain) highlights the risk of the introduction of new Flaviviruses where competent mosquito vectors are present, such as Aedes (A.) albopictus. It is important to note that none of the recent Flavivirus outbreaks have been predicted and that factors contributing to emergences are not well understood. For many of the less studied Flaviviruses the potential contribution of various vertebrate species to the maintenance of the virus is incompletely understood (Go et al, 2014). The susceptibility of animals living in close proximity to man such as domestic animals and livestock are important
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