Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis

摘要: A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus serious public health concern. EV71 causes Hand, Foot and Mouth Disease has been associated with neurological complications in young children. Our limited understanding the mechanisms involved its neuropathogenesis hampered development effective therapeutic options. Here, using a two-dimensional proteomics approach combined mass spectrometry, we have identified unique panel host proteins that were differentially dynamically modulated during infection motor-neuron NSC-34 cells, which are found at neuromuscular junctions where believed to enter central nervous system. Meta-analysis previously published studies neuroblastoma or muscle cell lines revealed minimal overlapping suggests host-pathogen interactions cells. Among candidate proteins, focused our attention on prohibitin (PHB), protein multiple cellular functions target anti-cancer drug Rocaglamide (Roc-A). We demonstrated surface-expressed PHB entry into neuronal cells specifically, while membrane-bound mitochondrial associates replication complex facilitates viral replication. Furthermore, Roc-A treatment EV71-infected reduced significantly yields. However, inhibitory effect was not through blocking CRAF/MEK/ERK pathway reported. Instead, treated had lower mitochondria-associated ATP levels correlated impaired mitochondria integrity. In vivo, mice survived longer than vehicle-treated animals loads their spinal cord brain, whereas titers limb muscles comparable controls. Together, this study uncovers first factor specifically potential limit complications.