Immunopathogenesis

*Dengue Fever in a One Health Perspective*

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**Chapter 4**

Responses

**Abstract**

Dengue Immunopathogenesis: A

Crosstalk between Host and Viral

Part I - Dengue Virus Tropism,

Host Innate Immune Responses,

Factors Leading to Disease:

and Subversion of Antiviral

*Henry Puerta-Guardo, Scott B. Biering, Eva Harris,* 

*Guadalupe Ayora-Talavera and Pablo Manrique-Saide*

Dengue is the most prevalent emerging mosquito-borne viral disease, affecting more than 40% of the human population worldwide. Many symptomatic dengue virus (DENV) infections result in a relatively benign disease course known as dengue fever (DF). However, a small proportion of patients develop severe clinical manifestations, englobed in two main categories known as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Secondary infection with any of the four dengue virus serotypes (DENV1, -2, -3, and -4) is a risk factor to develop severe forms of dengue disease. DSS is primarily characterized by sudden and abrupt endothelial dysfunction, resulting in vascular leak and organ impairment, which may progress to hypovolemic shock and death. Severe DENV disease (DHF/ DSS) is thought to follow a complex relationship between distinct immunopathogenic processes involving host and viral factors, such as the serotype cross-reactive antibody-dependent enhancement (ADE), the activation of T cells and complement pathways, the phenomenon of the *cytokine storm*, and the newly described viral toxin activity of the nonstructural protein 1 (NS1), which together play critical roles in inducing vascular leak and virus pathogenesis. In this chapter that is divided in two parts, we will outline the recent advances in our understanding of DENV pathogenesis, highlighting key viral-host interactions and discussing how these interactions may contribute to DENV immunopathology and the development of vascular leak, a hallmark of severe dengue. *Part I* will address the general features of the DENV complex, including the virus structure and genome, epidemiology, and clinical outcomes, followed by an updated review of the literature describing the host innate immune strategies as well as the viral mechanisms acting against and in

*Norma Pavia-Ruz, Gonzalo Vázquez-Prokopec,* 

favor of the DENV replication cycle and infection.
