Progress and challenges in development of animal models for dengue virus infection

ABSTRACTThe severity of the dengue epidemic is on the rise, with its geographic range had expanded to southern Europe by 2024. In this August, the WHO updated the pathogens that could spark the next pandemic, dengue virus was on the list. Vaccines and drugs serve as powerful tools for both preventing dengue infections and treating patients. Animal models play a pivotal role in vaccine development and drug screening. Available potential susceptible animals, including non-human primates, rodents, pigs, and tree shrews, have been extensively explored to establish animal models of dengue disease. Despite significant advancements, there are still notable limitations. Different animal models exhibit distinct constraining factors such as viraemia, host susceptibility, immune function of the host, clinical symptoms, ADE (antibody-dependent enhancement) phenomena, cytokine storm response to various serotypes and strain variations. Furthermore, despite extensive research on the dengue virus receptor in recent years, genetically modified animal models immunocompetent harbouring dengue virus susceptibility receptors have not yet been available. This work reviewed the research progress of dengue virus receptors and dengue animal models, suggesting that the development of genetically modified murine models expressing dengue virus functional receptors may hold a promise for future dengue disease research, especially for its vaccine development.