Enterovirus infections of the central nervous system

Abstract

Enteroviruses (EV) frequently infect the central nervous system (CNS) and induce neurological diseases. Although the CNS is composed of many different cell types, the spectrum of tropism for each EV is considerable. These viruses have the ability to completely shut down host translational machinery and are considered highly cytolytic, thereby causing cytopathic effects. Hence, CNS dysfunction following EV infection of neuronal or glial cells might be expected. Perhaps unexpectedly given their cytolytic nature, EVs may establish a persistent infection within the CNS, and the lasting effects on the host might be significant with unanticipated consequences. This review will describe the clinical aspects of EV-mediated disease, mechanisms of disease, determinants of tropism, immune activation within the CNS, and potential treatment regimes.

Dominant CD4‐dependent RNA‐dependent RNA polymerase‐specific T‐cell responses in children acutely infected with human enterovirus 71 and healthy adult controls

“…3,4 EV71 has recently emerged as an increasingly important neurotrophic enterovirus in the postpoliomyelitis eradication era. 5,6 In a previous study, we demonstrated that EV71 accounted for approximately 94Á4% of the fatal cases of HFMD. 7 At present, there are no effective antiviral medications 8 and no prophylactic vaccine against EV71 infection.…”

“…9 EV71 was shown to be responsible in China for most of the fatalities associated with severe neurological manifestations ranging from aseptic meningitis to acute flaccid paralysis and brainstem encephalitis in children < 5 years of age. 6,10 Chang et al 11 reported that an extensive analysis of clinical observations showed that humoral immunity did not differ significantly among cases of different clinical severity, and most of the severe EV71 cases had a lower cellular T helper type 1 cytokine level plus a weaker lymphocyte proliferation response. The cellular and humoral immune responses, such as represented by T cells and the interleukin-6 (IL-6) driven response, are both essential for decreasing the viral load and mortality in EV71-infected mice.…”

Distinct neural stem cell tropism, early immune activation, and choroid plexus pathology following coxsackievirus infection in the neonatal central nervous system

“…14 The induction of a family of chemokines that included CCL12 was observed as early as 12 h PI. 14 Our recent studies suggested that NPSCs and neurogenic regions of the CNS may support persistent CVB3 infection, 22,24 and infected mice surviving infection may suffer a chronic depletion of neural stem cells. 46 Here, we directly compared neural stem cell tropism for both CVB3 and LCMV.…”

“…[19][20][21] Our laboratory has previously shown that CVB3 preferentially targets NPSCs in culture and in the neonatal host presumably owing to their undifferentiated status and high proliferative index. 20,[22][23][24] In addition, we described the recruitment of unique nestin þ myeloid cells into the CNS following CVB3 infection. 14 These cells were highly susceptible to infection and assisted in the dissemination of infectious virus into the neurogenic regions of the neonatal CNS at early time points.…”

“…16,25,28,29 We hypothesize that a direct comparison of these two viruses during early infection of the neonatal CNS may help determine previously unidentified targets of infection, illuminate the neonatal host immune response following early infection, and clarify the mechanism of viral pathogenesis. The brains of 1-day-old CVB3 and LCMVinfected mice were analyzed for gene expression changes at 12,24, and 48 h post infection (PI) utilizing Illumina BeadArray Technology (MouseWG-6 v2 Expression Beadchips) in order to reveal the global neonatal host response for both neurotropic viral infections. In addition, we sought to examine the effects of viral infection upon the choroid plexus by histology, TUNEL assay, and fluorescence microscopy utilizing well-characterized markers of choroid plexus function.…”