Metabolic characteristics in orthoflaviviral infections: unveiling pathogenic mechanisms and therapeutic targets

Abstract Infections caused by mosquito-borne viruses such as Dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) have become a global public health issue. However, due to the unclear pathogenic mechanisms, there are currently no specific treatments available for patients infected with these orthoflaviviruses in clinical practice. Metabolomics provides distinct advantages for characterizing infection features and deciphering disease pathogenesis. Therefore, this review summarizes relevant literature on mosquito-borne viruses metabolomics, with a particular focus on elucidating the metabolic characteristics of cells infected by orthoflaviviruses. By conducting a comparative analysis of the metabolomics data from different sample sources infected with DENV, ZIKV, and JEV, we found that several metabolic pathways involved in viral infection, replication, and pathogenesis are commonly disrupted in the metabolomics data of these orthoflaviviruses. These pathways include the reprogramming of lipid metabolism, interference with energy metabolism, and the induction of host inflammatory responses. These findings identify key targets for subsequent mechanistic studies on the persistent replication and transmission of orthoflaviviruses in mosquito vectors and their ability to cause severe pathology in human hosts. Further elucidations of the above mechanisms could provide an effective scheme for preventing orthoflaviviral transmission in mosquito vectors and treating orthoflaviviral infections. In addition, studying these metabolomic changes in human hosts of orthoflaviviral infections may be able to provide relevant biomarkers for accurate diagnosis of the disease.