**Author details**

*Dengue Fever in a One Health Perspective*

can be considered during vaccine trial interventions.

To the Canadian Institutes of Health Research and the International Development Research Centre (Projects 108,412 & 109,071–002) and the Fondo Mixto CONACYT-Gobierno del Estado de Yucatan (Project

**Acknowledgements**

YUC-2017-2103-01-556).

high circulating levels correlated with the appearance of severe dengue disease, was reported to modulate complement pathways, facilitating virus infection via immune evasion strategies. NS1 has demonstrated to exert an amazing array of different functions. More recently, NS1 was demonstrated to be a multitasking protein of the flavivirus genus which could directly cause disruption of the EGL and endothelial cell-to-cell contacts, two main components of the homeostasis balance in the microvasculature, and to induce the production of soluble immunoregulators resulting in increased endothelial barrier dysfunction and vascular leakage. This evidence provides new insights into the biology of the multifaceted NS1 protein of flavivirus that may improve the understanding of the flavivirus pathogenesis, strongly supporting the inclusion of NS1 protein in flavivirus vaccine development and the generation of new targets for future therapies against flavivirus infections. In conclusion, the immunopathogenesis of DENV infection represents an extraordinarily complex interplay between several viral and host factors that together contribute intimately to the activation of distinct immunopathological processes that although were intended to control the viral infection and replication, instead unleash an unbalanced host immune response leading to increased endothelial dysfunction and vascular leakage, reflected in the appearance of dengue severe manifestations. As no effective vaccine or antiviral therapy are available to treat either prophylactically or therapeutically the DENV infection, the incidence of dengue disease is expanding globally and continues to threat the public health services worldwide, particularly in endemic areas. An increased understanding of DENV immunopathogenesis mechanisms involved in the development of severe disease, their components, biological triggers, and their potential connections will assist not only the development of potentially more effective novel therapeutic interventions but also the understanding of dengue vaccine efficacy or vaccine adverse events that

**108**

Henry Puerta-Guardo1 \*, Scott B. Biering2 , Eva Harris2 , Norma Pavia-Ruz3 , Gonzalo Vázquez-Prokopec4 , Guadalupe Ayora-Talavera3 and Pablo Manrique-Saide1

1 Collaborative Unit for Entomological Bioassays and Laboratory for Biological Control of *Aedes aegypti*, Campus of Biological and Agricultural Sciences, Universidad Autonoma de Yucatan, Merida, Yucatan, Mexico

2 Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, USA

3 Centro de Investigaciones Regionales, Dr. Hideyo Noguchi, Universidad Autonoma de Yucatan, Merida, Yucatan, Mexico

4 Department of Environmental Sciences, Emory University, Atlanta, Georgia, USA

\*Address all correspondence to: hpuertaguardo@gmail.com

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
