Dengue Virus-Susceptible Animal Models: Research Progress, Core Bottlenecks, and Future Perspectives

Area of Science:

• Virology
• Immunology
• Pathology
• Epidemiology

Background:

• Dengue fever (DF), caused by dengue virus (DENV), is a significant global health threat transmitted by Aedes mosquitoes, affecting nearly 4 billion people.
• The WHO classifies DENV as a potential pandemic pathogen due to severe manifestations like hemorrhage and shock.
• Existing control strategies are hampered by vaccine limitations, lack of specific antivirals, and insecticide resistance.

Purpose of the Study:

• To systematically review current and potential animal models for dengue virus research.
• To analyze the characteristics, applications, and limitations of various susceptible animal models.
• To provide insights for developing improved animal models for dengue virus research.

Main Methods:

• Review of existing literature on animal models for dengue virus.
• Analysis of model systems including non-human primates, mice, pigs, tree shrews, and bats.
• Evaluation of models based on immune status, genetic modification, and species-specific traits.

Main Results:

• Mouse models are widely used due to flexibility and cost, while non-human primates are crucial for preclinical vaccine testing due to human immune response homology.
• Current models inadequately simulate severe dengue phenotypes, immune responses, viral receptor mechanisms, and lack standardized protocols.
• Key severe mechanisms like antibody-dependent enhancement (ADE) and cytokine storms are difficult to replicate accurately.

Conclusions:

• Future dengue virus-susceptible animal models require intact immunity, broad susceptibility, and accurate simulation of clinical features, especially ADE and cytokine storms.
• Development of standardized experimental systems and evaluation criteria is essential for accurate disease modeling.
• Optimized animal models are critical for advancing dengue research, prevention, control technologies, and clinical applications.