Emerging Concepts in Dengue Pathogenesis and Host Innate Immune Response

Dengue is a systemic arthropod-borne viral disease present in over 100 countries. Dengue virus infections are a serious health concern around the world. In a recent modeling-based report it was estimated that around half of the world’s population is at the risk of this disease. Dengue fever is generally self‐limiting, however, in certain cases, it can progress to more complicated forms, such as Dengue Haemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) with high mortality rates, as well as significant economic burdens. Moreover, subsequent infections of Dengue are more severe due to a phenomenon known as Antibody-Dependent Enhancement (ADE), where pre-existing antibodies help the virus with different serotypes to infect monocytes more efficiently thereby contributing to the enhanced pathogenesis and spread of the disease. Recent data further suggest that the non-structural protein-1 (NS1) is responsible for most of the complications that arise during severe Dengue infections. Apart from NS1 mediated pathogenesis, the Dengue virus may also inhibit host innate immune pathways. Dengue infection induces the host’s RLR, as well as the cGAS-STING axis of the innate immune signaling pathway. However, dengue infection may also lead to the inhibition of the IRF and the STAT family of proteins, thereby leading to the suppression of the host innate immune pathways. Furthermore, it has been reported that all non-structural proteins of the Dengue virus play a key role in inhibiting host innate immune responses by targeting diverse members of these pathways. Additionally, Dengue sub genetic RNA also plays a vital role in inhibiting host RLR signaling.

There are no specific therapies against this virus and novel antivirals to inhibit Dengue are highly desired. Even though multiple strategies are used to design vaccine candidates against this virus, these approaches have failed due to the complexity and epidemiology of the disease. To this end, there is an urgent need to identify novel cellular pathways and therapies that can be applied for the inhibition of this virus.

The Guest-Editors of this Research Topic welcome original research articles, perspectives, methods, and reviews, and aim to assemble a collection of articles highlighting, but not limited to:
• Current advancements in Dengue virus pathogenesis
• Innate immune responses to Dengue infections
• Diagnosis and treatment of Dengue
This will favor a better understanding of these aspects that will enable the development of novel therapies and better management of the disease.