Immune-Mediated Pathogenesis in Dengue Virus Infection

Abstract

Dengue virus (DENV) infection is one of the major public health concerns around the globe, especially in the tropical regions of the world that contribute to 75% percent of dengue cases. While the majority of DENV infections are mild or asymptomatic, approximately 5% of the cases develop a severe form of the disease that is mainly attributed to sequential infection with different DENV serotypes. The severity of dengue depends on many immunopathogenic mechanisms involving both viral and host factors. Emerging evidence implicates an impaired immune response as contributing to disease progression and severity by restricting viral clearance and inducing severe inflammation, subsequently leading to dengue hemorrhagic fever and dengue shock syndrome. Moreover, the ability of DENV to infect a wide variety of immune cells, including monocytes, macrophages, dendritic cells, mast cells, and T and B cells, further dysregulates the antiviral functions of these cells, resulting in viral dissemination. Although several risk factors associated with disease progression have been proposed, gaps persist in the understanding of the disease pathogenesis and further investigations are warranted. In this review, we discuss known mechanisms of DENV-mediated immunopathogenesis and its association with disease progression and severity.

Meeting the Challenge of Controlling Viral Immunopathology

“…Formation of immune complexes (virus-antibody) depositing in blood vessels, triggering inflammation and vascular leakage. Cytokine storm resulting from infection of inflammatory cells B cells, defective CD4+ and CD8+ T cells, macrophages; Dengue-specific antibodies, TNF-α, IL-2, IL-6 [4][5][6] EBV Potential molecular mimicry triggering autoimmune reactions against self-tissues CD4+ and CD8+ T cells, B cells; EBV-specific antibodies [7,8] HBV Chronic infection triggers CD8-mediated inflammation, leading to liver damage.…”

Abnormal glucose metabolism in virus associated sepsis

“…These studies may provide future guidance for the treatment of DENV by targeting metabolic regulation ( Lee et al., 2020 ). DENV infection can disrupt the ability of immune cells, including mast cells, dendritic cells, monocytes, macrophages, and T and B cells, to defend against infections, thereby exacerbating viral replication and transmission ( Khanam et al., 2022 ). Monocytes deficient in G6PD (glucose-6-phosphate dehydrogenase) exhibited a significant elevation in the rate of DENV2 infection.…”

The One Health Concept

“…Reported case fatality rates for these infections vary but can be around 10%. There are 4 serotypes of dengue virus and Dengue haemorrhagic fever (DHF) occurs when a person who has recovered from a previous infection with one serotype is infected with a different one; this can lead to an overwhelming inappropriate immune response [ 79 ]. The reported incidence of both these diseases have been increasing during the 21st Century.…”