Key result
Oral probiotic formulation suppresses EV71 viral replication and reduces multi-organ damage in preclinical model.
Why the study?
The absence of a simple and reliable oral infection model has impeded investigations into EV71 pathogenesis and the development of antiviral interventions.
An established oral EV71 infection mouse model reveals route-dependent pathogenesis and allows for the preclinical evaluation of intestinally targeted interventions, such as probiotics, which cannot be adequately assessed in standard intraperitoneal models.
Enterovirus 71 (EV71) is one of the major pathogens responsible for hand-foot-and-mouth disease in children and is associated with severe neurological complications, including death. Despite the fact that EV71 naturally infects humans through the oral route, the absence of a simple and reliable oral infection model has significantly impeded investigations into its pathogenesis and the development of antiviral interventions. In this study, we established a robust oral EV71 infection model in widely used immunocompetent BALB/c mice, employing a clinical isolate devoid of adaptive mutations. Mice infected via the oral route developed disease progression and clinical, as well as pathological features that closely recapitulate those observed in human infection. We further identified marked differences in viral dissemination and host immune responses between oral and intraperitoneal inoculation, underscoring the importance of physiologically relevant oral infection models for elucidating EV71 pathogenesis. In addition, the anti-EV71 candidate drug rupintrivir showed reduced efficacy in the oral infection model compared with the intraperitoneal model. Notably, this oral model enables evaluation of therapies designed to block intestinal viral infection—a capability lacking in intraperitoneal models. Using this platform, we assessed an intestinal probiotic blockade therapy for the first time. Our findings demonstrate that the probiotic formulation effectively suppresses viral replication and alleviates pathological damage in the spleen, lungs, kidneys, and other organs, providing a scientific basis for developing probiotic-based therapeutic strategies against viral infections. IMPORTANCE The restricted host tropism of enterovirus 71 (EV71) has limited the development of animal models that accurately recapitulate human disease. Here, we demonstrate for the first time that the clinically isolated EV71-GZCII strain successfully infects 14-day-old immunocompetent BALB/c mice via oral gavage, establishing a physiologically relevant model that addresses this critical gap. Orally infected mice displayed distinct viral dissemination patterns and host immune responses compared with intraperitoneal models, highlighting the critical role of infection route in EV71 pathogenesis. Using this system, we evaluated the in vivo therapeutic efficacy of the 3C protease inhibitor rupintrivir and found that its apparent efficacy is strongly influenced by the route of infection. Furthermore, we employed this oral model to assess probiotic-based antiviral therapy, revealing effective suppression of viral replication and pathology. Unlike intraperitoneal systems, this model uniquely enables evaluation of intestinal interventions, providing a robust platform for EV71 research and therapy development.
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Ma et al. (2026) studied Enterovirus 71 (EV71) infection. Rupintrivir and Intestinal probiotic formulation (Siliankang) vs. Vehicle or PBS was evaluated on Survival rate, clinical symptom scores, and tissue viral RNA loads. Establishment of an oral EV71 infection model in immunocompetent mice demonstrated that an intestinal probiotic formulation effectively suppressed viral replication and alleviated multi-organ pathological damage.
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