Dataset Information

Monocyte-Derived Dendritic Cells as Model to Evaluate Species Tropism of Mosquito-Borne Flaviviruses.

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-? 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.

SUBMITTER: Garcia-Nicolas O

PROVIDER: S-EPMC6360178 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Monocyte-Derived Dendritic Cells as Model to Evaluate Species Tropism of Mosquito-Borne Flaviviruses.

García-Nicolás Obdulio O Lewandowska Marta M Ricklin Meret E ME Summerfield Artur A

Frontiers in cellular and infection microbiology 20190128

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 m ...[more]

PMID: 30746342

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Project description:Given the significant impact of mosquito-borne flaviviruses (MBFVs) on both human and animal health, predicting their dynamics and understanding their transmission cycle is of the utmost importance. Usually, predictions about the distribution of priority pathogens, such as Dengue, Yellow fever, West Nile Virus and St. Louis encephalitis, relate abiotic elements to simple biotic components, such as a single causal agent. Furthermore, focusing on single pathogens neglects the possibility of interactions and the existence of common elements in the transmission cycles of multiple pathogens. A necessary, but not sufficient, condition that a mosquito be a vector of a MBFV is that it co-occurs with hosts of the pathogen. We therefore use a recently developed modeling framework, based on co-occurrence data, to infer potential biotic interactions between those mosquito and mammal species which have previously been identified as vectors or confirmed positives of at least one of the considered MBFVs. We thus create models for predicting the relative importance of mosquito species as potential vectors for each pathogen, and also for all pathogens together, using the known vectors to validate the models. We infer that various mosquito species are likely to be significant vectors, even though they have not currently been identified as such, and are likely to harbor multiple pathogens, again validating the predictions with known results. Besides the above "niche-based" viewpoint we also consider an assemblage-based analysis, wherein we use a community-identification algorithm to identify those mosquito and/or mammal species that form assemblages by dint of their significant degree of co-occurrence. The most cohesive assemblage includes important primary vectors, such as A. aegypti, A. albopictus, C. quinquefasciatus, C. pipiens and mammals with abundant populations that are well-adapted to human environments, such as the white-tailed deer (Odocoileus virginianus), peccary (Tayassu pecari), opossum (Didelphis marsupialis) and bats (Artibeus lituratus and Sturnira lilium). Our results suggest that this assemblage has an important role in the transmission dynamics of this viral group viewed as a complex multi-pathogen-vector-host system. By including biotic risk factors our approach also modifies the geographical risk profiles of the spatial distribution of MBFVs in Mexico relative to a consideration of only abiotic niche variables.

Dataset Information

Monocyte-Derived Dendritic Cells as Model to Evaluate Species Tropism of Mosquito-Borne Flaviviruses.

Publications

Monocyte-Derived Dendritic Cells as Model to Evaluate Species Tropism of Mosquito-Borne Flaviviruses.

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