Neurotropic RNA viruses pose a growing concern due to their ability to invade and damage the central nervous system (CNS), leading to a wide spectrum of neurological disorders [1]. Flaviviruses, which are vector-borne single-stranded positive-sense RNA viruses, have emerged as major neurotropic pathogens with global impact. Among them, Japanese encephalitis virus (JEV), West Nile virus (WNV), Zika virus (ZIKV), and Dengue virus (DENV) are the most clinically relevant and have been reported to cause a range of neurological complications in humans during the acute phase of infection 2, 3, 4. Notably, some patients experience long-term cognitive impairment post-recovery from acute flavivirus infections 2, 5.

Another group of neurotropic RNA viruses of clinical concerns is the Enteroviruses. Although there are many predominant types of neurotropic enteroviruses, the most prevalent ones associated with distinct CNS pathology are the Enterovirus A71 (EV-A71) and coxsackieviruses A10 and A16 (CV-A10 and CV-A16) 6, 7, 8. Depending on the virus subgenotype and host factors, it can induce severe neurological complications, such as meningitis and encephalitis [6]. Currently, no interventions are available as these neurotropic viruses vary widely in their routes of CNS entry, cellular tropism, and neuropathological outcomes [9]. Therefore, it remains imperative to understand these mechanisms for the advancement and development of antiviral strategies and vaccines.

In this review, we will focus on recent findings within the past 2 years in dissecting the mechanisms of clinically relevant neurotropic flaviviruses and enteroviruses from entry to infection (Table 1 and Figure 1) in inducing neurological complications to encompass a wider perspective on CNS infections and their consequences.