Editorial: Molecular Pathogenesis of Enteroviruses: Insights into Viral-Host Interactions, Pathogenic Mechanisms, and Microbiome Dynamics

Jade Lee Lee Teng^1*Shubhada Bopegamage^2*Man Lung Yeung^3*

• ¹Faculty of Dentistry, The University of Hong Kong, Sai Ying Pun, Hong Kong, SAR China
• ²Faculty of Medicine, Institute of Laboratory Medicine, Slovak Medical University, Limbova 12, 83303 Bratislava, Slovakia
• ³Department of Microbiology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, SAR China

Enterovirus, a genus of small, non-enveloped RNA viruses within the Picornaviridae family, are among the most pervasive and clinically significant pathogens worldwide (1,2).With over 100 serotypes identified-including poliovirus, coxsackieviruses, echoviruses, and enterovirus A71 (EV-A71)-these viruses exhibit remarkable genetic diversity and adaptability, enabling them to infect millions annually. Their clinical impact spans acute neurological, respiratory, and systemic diseases, such as encephalitis, acute flaccid paralysis, meningitis, and hand, foot, and mouth disease (HFMD), as well as insidious links to chronic conditions like type 1 diabetes (T1D), chronic fatigue syndrome, and idiopathic dilated cardiomyopathy (3)(4)(5). The ability of enteroviruses to cause such a wide spectrum of diseases is attributed to their range of cell/organ tropism, capacity to evade the immune system (6), persist in host tissues (7), and exploit various cellular pathways for replication and dissemination (8,9).Enteroviruses have been associated with severe outbreaks that pose significant public health challenges (10)(11)(12). For instance, outbreaks of HFMD caused by EV-A71 have led to substantial morbidity and mortality globally (13), necessitating urgent public health responses and vaccine development efforts. The global distribution and high mutation rates of these viruses further complicate control measures, making it imperative to understand their molecular biology and pathogenesis comprehensively.Globally, the public health systems grapple with emerging viral threats, understanding the molecular intricacies of enterovirus pathogenesis, host interactions, and microbiome dynamics is not just urgent-it is a cornerstone for developing targeted therapies and preventive strategies. This special issue, titled "Molecular Pathogenesis of Enteroviruses:Insights into Viral-Host Interactions, Pathogenic Mechanisms, and Microbiome Dynamics," compiles original research articles that shed light on ongoing outbreaks in different geographical regions and identify factors that may contribute to the pathogenesis of enteroviruses. Coxsackievirus infections have been associated to T1D, which involve triggering mechanisms leading to autoimmune destruction process of insulin-producing beta cells. In Bonfim's study, the authors explored the role of N6-methyladenosine (m6A) RNA modification in coxsackievirus B1 (CVB1) replication. They found that downregulating m6A writers increased CVB1 replication, while downregulating m6A erasers decreased it. This highlights the critical role of m6A in CVB1 replication and suggests that targeting the m6A machinery could be a potential therapeutic strategy for controlling coxsackievirus B (CVB) infections and subsequently T1D. In summary, this special issue highlights the significance of enteroviruses. The scientific evidence presented in this Research Topic has identified key factors that may contribute to the pathogenesis of enterovirus-related diseases, further emphasizing the importance of these viruses in light of the ongoing outbreak. This new knowledge can enhance our understanding and development effective disease management strategies to combat these critical viral infections.