Current Understanding of the Role of T Cells in Chikungunya, Dengue and Zika Infections.

Maheshi Mapalagamage,Daniela Weiskopf,Aruna Dharshan De Silva,Alessandro Sette

doi:10.3390/v14020242

Abstract

Arboviral infections such as Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) are a major disease burden in tropical and sub-tropical countries, and there are no effective vaccinations or therapeutic drugs available at this time. Understanding the role of the T cell response is very important when designing effective vaccines. Currently, comprehensive identification of T cell epitopes during a DENV infection shows that CD8 and CD4 T cells and their specific phenotypes play protective and pathogenic roles. The protective role of CD8 T cells in DENV is carried out through the killing of infected cells and the production of proinflammatory cytokines, as CD4 T cells enhance B cell and CD8 T cell activities. A limited number of studies attempted to identify the involvement of T cells in CHIKV and ZIKV infection. The identification of human immunodominant ZIKV viral epitopes responsive to specific T cells is scarce, and none have been identified for CHIKV. In CHIKV infection, CD8 T cells are activated during the acute phase in the lymph nodes/blood, and CD4 T cells are activated during the chronic phase in the joints/muscles. Studies on the role of T cells in ZIKV-neuropathogenesis are limited and need to be explored. Many studies have shown the modulating actions of T cells due to cross-reactivity between DENV-ZIKV co-infections and have repeated heterologous/homologous DENV infection, which is an important factor to consider when developing an effective vaccine.

Highlights

Chikungunya virus (CHIKV), Dengue virus (DENV) and Zika virus (ZIKV) are widely distributed arboviruses transmitted through Aedes mosquitos, causing a massive disease burden in tropical and subtropical areas of the world
The lack of knowledge of CHIKV and ZIKV immunodominant epitopes hampers progress in the field, as the role of T cell responses in disease protection and immunopathology cannot be broadly evaluated, and the performance of different vaccines in terms of induction of4 of immune responses in human remains undetermined
A recent study mapped 93 human ZIKV T cell epitopes cross-reactive with DENV using in vitro expanded T cells taken from DENV-exposed, ZIKV-unexposed donors

Summary

Introduction

Chikungunya virus (CHIKV), Dengue virus (DENV) and Zika virus (ZIKV) are widely distributed arboviruses transmitted through Aedes mosquitos, causing a massive disease burden in tropical and subtropical areas of the world. CHIKV is an alphavirus (Togaviridae family), and DENV and ZIKV are flaviviruses (Flaviviridae family) [1]. These virus infections are endemic in largely overlapping geographical regions. They initially emerged in Africa, where CHIKV, DENV and ZIKV infections are common (Figure 1). Thisthe map global transmission of CHIKV, and ZIKV. The and mapZIKV was created using freeshows onlinethe tool

17 December

Understanding the

Understanding the Role of T Cells in CHIKV

T Cell Response in DENV Infection

Findings

Role of T Cells Response in ZIKV Infection