Molecular Pathogenicity of Enteroviruses Causing Neurological Disease

Abstract

Enteroviruses are single-stranded positive-sense RNA viruses that primarily cause self-limiting gastrointestinal or respiratory illness. In some cases, these viruses can invade the central nervous system, causing life-threatening neurological diseases including encephalitis, meningitis and acute flaccid paralysis (AFP). As we near the global eradication of poliovirus, formerly the major cause of AFP, the number of AFP cases have not diminished implying a non-poliovirus etiology. As the number of enteroviruses linked with neurological disease is expanding, of which many had previously little clinical significance, these viruses are becoming increasingly important to public health. Our current understanding of these non-polio enteroviruses is limited, especially with regards to their neurovirulence. Elucidating the molecular pathogenesis of these viruses is paramount for the development of effective therapeutic strategies. This review summarizes the clinical diseases associated with neurotropic enteroviruses and discusses recent advances in the understanding of viral invasion of the central nervous system, cell tropism and molecular pathogenesis as it correlates with host responses.

Molecular Epidemiology of Enterovirus in Children with Central Nervous System Infections

“…CV-B5 and echoviruses (6, 11, 30) are commonly associated with both encephalitis and aseptic meningitis, as it was also identified in our population [ 44 ]. Likewise, CV (A5, A7, A16, B2, B3, B4) and echoviruses (14, 16, 25, 31) are all implicated in cases of meningitis [ 44 , 45 ]. However, in our population, E16 was not only associated with meningitis but also with two cases of neonatal sepsis-like disease.…”

Pediatric Enteroviral Central Nervous System Infections in Bialystok, Poland: Epidemiology, Viral Types, and Drivers of Seasonal Variation

“…Animal models and clinical observations have revealed different host immune responses to infections with different enteroviruses [ 39 ]. In this study infections caused by CVB5 were characterized by more common and longer duration of fever, higher CSF pleocytosis secondary to lymphocytosis and lower CRP concentrations, when compared to other EV types.…”

Viral meningitis: an overview

“…They can also undergo vertical transmission from an infected mother to her infant by crossing the placenta or through breastfeeding [ 55 ]. As the virus enters the body, it replicates mainly in the epithelium cells of the nasopharynx and the oropharyngeal and intestinal mucosa [ 56 ]. In most cases, the virus enters the body through the oral-fecal route until it reaches the lower gastrointestinal (GI) tract, where it binds to a specific receptor on the surface of enterocytes and crosses the lining of the intestine, reaching the Peyer’s patches, where it continues its replication [ 57 ].…”

“…For a better understanding of the pathogenesis of meningitis, it is important to investigate the interplay between EV-infected cells and the progression of neurological disease, since each cell produces a different response upon infection. Various studies have shown that EVs infect different neural cells, such as glia cells and astrocytes [ 56 ]. For example, EV-71 and coxsackievirus B have been detected in undifferentiated neural progenitor cells in mice after infection [ 58 , 59 ].…”