Mammalian animal models for dengue virus infection: a recent overview

Mohammad Enamul Hoque Kayesh,Kyoko Tsukiyama-Kohara

doi:10.1007/s00705-021-05298-2

Mohammad Enamul Hoque Kayesh, Kyoko Tsukiyama-Kohara

Open Access

https://doi.org/10.1007/s00705-021-05298-2

Copy DOI

Abstract

Dengue, a rapidly spreading mosquito-borne human viral disease caused by dengue virus (DENV), is a public health concern in tropical and subtropical areas due to its expanding geographical range. DENV can cause a wide spectrum of illnesses in humans, ranging from asymptomatic infection or mild dengue fever (DF) to life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue is caused by four DENV serotypes; however, dengue pathogenesis is complex and poorly understood. Establishing a useful animal model that can exhibit dengue-fever-like signs similar to those in humans is essential to improve our understanding of the host response and pathogenesis of DENV. Although several animal models, including mouse models, non-human primate models, and a recently reported tree shrew model, have been investigated for DENV infection, animal models with clinical signs that are similar to those of DF in humans have not yet been established. Although animal models are essential for understanding the pathogenesis of DENV infection and for drug and vaccine development, each animal model has its own strengths and limitations. Therefore, in this review, we provide a recent overview of animal models for DENV infection and pathogenesis, focusing on studies of the antibody-dependent enhancement (ADE) effect in animal models.

Highlights

Dengue, caused by dengue virus (DENV), is one of the most important arthropod-borne human viral infections in many tropical and subtropical areas [39, 128]
Substantial progress has been made in our understanding of dengue pathogenesis using different animal models of DENV infection, none of the existing animal models represents the ideal model for the study of the pathogenesis of dengue
Data obtained from the study of DENV infection and pathogenesis in animal models should be regarded with caution

Summary

Introduction

Dengue, caused by dengue virus (DENV), is one of the most important arthropod-borne human viral infections in many tropical and subtropical areas [39, 128]. The establishment of a small-animal model is of great importance for the study of dengue, including research on host-virus interactions, disease pathogenesis, and antiviral and vaccine development. A suitable small-animal model whose infection manifestations resemble those of human dengue infection is critical, and the development of such a model has been long sought and challenging In this context, several animal models have been investigated in DENV infection and pathogenesis studies [139], including mouse models, non-human primate (NHP) models, swine models, and a recently reported tree shrew model, as discussed in the sections below. A recent study showed that C57BL/6 mice sequentially infected with non-mouse-adapted DENV-1 (strain Puerto Rico/94) and DENV-2 (strain Tonga/74) had a low platelet count, internal hemorrhages, and increased liver enzymes in serum [119].

Limitations

Findings

Conclusions