Nuclear Receptor Ligands in Flavivirus Infection Control

Flavivirus infectious diseases, such as dengue fever, chikungunya, and West Nile and Zika virus, represent a public health concern worldwide. The role of nuclear receptor ligands in the prevention and control of the severity of such vector-borne diseases is yet to be fully elucidated. This chapter provides systematically reviewed information on the role of nuclear receptor ligands in the control of flavivirus infections. Furthermore, we aim to assess the effect of modulating the function of these receptors in influencing disease severity. We conducted a comprehensive search in PubMed, Ovid Medline, Embase, and Embase Classic to extract human studies discussing the role of nuclear receptors and their ligands in flavivirus infections. Seventeen studies were extracted and included in this systematic review. Human studies pertaining to peroxisome proliferator-activated receptors (PPARs) suggest that antagonizing these receptors increases the susceptibility to viral infection. On the other hand, liver X receptors (LXRs) that are involved in cholesterol homeostasis may play a role in flavivirus infection control. LXR agonists have shown to inhibit viral replication via activating cholesterol export from infected cells. Studies on vitamin D receptor (VDR) ligands suggest that VDR polymorphism is associated with infection severity, e.g., in dengue fever. Vitamin D supplementation was shown to inhibit viral replication. One study focused on the reverse strand of erythroblastic leukemia viral oncogene homologue (REV-ERB) receptor and concluded that receptor agonists can markedly reduce both viral load and replication. In conclusion, modulating nuclear receptors can play a role in the control and prevention of flavivirus infectious diseases by either influencing the susceptibility to viral infection, inhibiting its replication, or affecting the disease severity.