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Genotype 4 strain of swine\n                    <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                    was used to inoculate Mongolian gerbils. Reverse transcription\u2013nested polymerase chain reaction (\n                    <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">nPCR<\/jats:styled-content>\n                    ),\n                    <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>\n                    , histopathology, ultrastructural pathology and enzyme immunohistochemistry method were conducted to investigate the replication and localization of\n                    <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                    in the central nervous system (\n                    <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>\n                    ) and the consequent pathological changes. Both positive\u2010 and negative\u2010strand\n                    <jats:styled-content style=\"fixed-case\">HEV RNA<\/jats:styled-content>\n                    was detectable in brain and spinal cord from 7 to 28 dpi (days postinoculation) via\n                    <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">nPCR<\/jats:styled-content>\n                    . Various pathological changes such as perineural invasion, neuron necrosis, microglia nodule, lymphocyte infiltration, perivascular cuff and myelin degeneration were observed in\n                    <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                    \u2010positive brains and spinal cords. Immunohistochemical (\n                    <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>\n                    ) staining targeting on\n                    <jats:styled-content style=\"fixed-case\">HEV ORF<\/jats:styled-content>\n                    2 protein revealed positive signals concentrated mainly in the cytoplasm of neuron, ependymal epithelium and choroid plexus area. Positive area density of\n                    <jats:styled-content style=\"fixed-case\">ZO<\/jats:styled-content>\n                    \u20101 (zonula occludens\u20101) in brain of\n                    <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                    \u2010positive gerbils decreased, while the\n                    <jats:styled-content style=\"fixed-case\">GFAP<\/jats:styled-content>\n                    (glial fibrillary acidic protein) expression was upregulated compared with control groups. These results provide strong evidence that\n                    <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                    is able to damage the blood\u2013brain barrier (\n                    <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>\n                    ), replicate in brain and spinal cord, and hammer the causative role of\n                    <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                    in the pathogenesis of neurologic disorders.\n                  <\/jats:p>","DOI":"10.1111\/jvh.12557","type":"journal-article","created":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T13:28:57Z","timestamp":1466688537000},"page":"930-939","source":"Crossref","is-referenced-by-count":81,"title":["Evidence of Hepatitis E virus breaking through the blood\u2013brain barrier and replicating in the central nervous system"],"prefix":"10.1111","volume":"23","author":[{"given":"R.","family":"Shi","sequence":"first","affiliation":[{"name":"Laboratory of Animal Pathology and Public Health Key Laboratory of Zoonosis of Ministry of Agriculture College of Veterinary Medicine China Agriculture University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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