The application and discovery of animal models in enterovirus research.

Enterovirus infection remains a significant global public health challenge, causing severe diseases such as hand, foot, and mouth disease (HFMD) and meningitis. Given the current lack of effective broad-spectrum antiviral therapies, it is important to investigate the pathogenic mechanisms of viruses using animal models in order to accelerate the development of intervention strategies. This review systematically examines the progress in the development of animal models for enterovirus research, with particular emphasis on non-human primates, rodents, and non-viral infection models. Non-human primates are considered ideal for studying natural enterovirus infections due to their high degree of physiological and immunological similarity to humans. Rodent models, while cost-effective and relatively easy to handle, often rely on the use of viruses with adaptive mutations or immunodeficient animals, which may not fully replicate the human immune response. Non-viral infection models can be used to obtain novel insights into virus-host interactions. Current challenges include the need to overcome discrepancies between animal models and human disease phenotypes, as well as the limitations imposed by the host specificity of viral strains. Future research should integrate multi-omics technologies, organoids, and artificial intelligence to optimize model construction, advance translational research, and provide precise tools for enterovirus prevention and control.