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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2019.00005

Monocyte-derived dendritic cells as model to evaluate species tropism of mosquito-borne flaviviruses

  • 1Immunology, Institute of Virology and Immunology (IVI), Switzerland
  • 2Department of Infectious diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Switzerland
  • 3Institute of Virology and Immunology (IVI), Switzerland
  • 4Abteilung für Notfallmedizin, Universitätsklinikum Bern, Switzerland

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.

Keywords: Flavivirus, dendritic cell, monocyte, Zoonoses, Tropism, innate immune response

Received: 31 Aug 2018; Accepted: 09 Jan 2019.

Edited by:

Alan G. Goodman, Washington State University, United States

Reviewed by:

Kui Li, University of Tennessee Health Science Center (UTHSC), United States
Fengwei Bai, University of Southern Mississippi, United States  

Copyright: © 2019 Summerfield, Lewandowska, Garcia-Nicolas and Ricklin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Artur Summerfield, Institute of Virology and Immunology (IVI), Immunology, Mittelhäusern, 3001, Bern, Switzerland, artur.summerfield@ivi.admin.ch