Current Understanding of the Pathogenesis of Dengue Virus Infection

Puneet Bhatt,Govindakarnavar Arunkumar,Muralidhar Varma,Sasidharan Pillai Sabeena

doi:10.1007/s00284-020-02284-w

Puneet Bhatt, Govindakarnavar Arunkumar + Show 2 more

Open Access

https://doi.org/10.1007/s00284-020-02284-w

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Abstract

The pathogenesis of dengue virus infection is attributed to complex interplay between virus, host genes and host immune response. Host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity as well as genetic factors are major determinants of disease susceptibility. NS1 protein and anti-DENV NS1 antibodies were believed to be responsible for pathogenesis of severe dengue. The cytokine response of cross-reactive CD4+ T cells might be altered by the sequential infection with different DENV serotypes, leading to further elevation of pro-inflammatory cytokines contributing a detrimental immune response. Fcγ receptor-mediated antibody-dependent enhancement (ADE) results in release of cytokines from immune cells leading to vascular endothelial cell dysfunction and increased vascular permeability. Genomic variation of dengue virus and subgenomic flavivirus RNA (sfRNA) suppressing host immune response are viral determinants of disease severity. Dengue infection can lead to the generation of autoantibodies against DENV NS1antigen, DENV prM, and E proteins, which can cross-react with several self-antigens such as plasminogen, integrin, and platelet cells. Apart from viral factors, several host genetic factors and gene polymorphisms also have a role to play in pathogenesis of DENV infection. This review article highlights the various factors responsible for the pathogenesis of dengue and also highlights the recent advances in the field related to biomarkers which can be used in future for predicting severe disease outcome.

Highlights

Dengue infection is a major public health problem and has been reported from the Americas, Africa, Southeast Asia, Europe, Western Pacific, and Eastern Mediterranean regions
DENV infection can have diverse presentations in different hosts, which cannot be explained by a single hypothesis alone
The recent results of the efficacy and safety trials of the CYD-TDV tetravalent dengue vaccine have reminded the research community that there is still a lot to learn with regard to understanding the pathogenesis and expression of protective immunity to DENV

Summary

Introduction

Dengue infection is a major public health problem and has been reported from the Americas, Africa, Southeast Asia, Europe, Western Pacific, and Eastern Mediterranean regions. This arboviral disease is found to be endemic in more than 100 countries and around 96 million infected individuals are symptomatic with varying levels of severity [1, 2].

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