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Direct intracranial inoculation of VRP into mice induced acute encephalitis with signs similar to the neuronal phase of wild-type VEE infection and other models of virus-induced encephalitis. Using the previously established VRP-mRNP tagging system, a new method to distinguish the host responses in infected cells from those in uninfected bystander cell populations, we detected a robust and rapid innate immune response in the central nervous system (CNS) by infected neurons and uninfected bystander cells. Moreover, this innate immune response in the CNS compromised blood-brain barrier integrity, created an inflammatory response, and directed an adaptive immune response characterized by proliferation and activation of microglia cells and infiltration of inflammatory monocytes, in addition to CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T lymphocytes. Taken together, these data suggest that a nai\u0308ve CNS has an intrinsic potential to induce an innate immune response that could be crucial to the outcome of the infection by determining the composition and dynamics of the adaptive immune response. Furthermore, these results establish a model for neurotropic virus infection to identify host and viral factors that contribute to invasion of the brain, the mechanism(s) whereby the adaptive immune response can clear the infection, and the role of the host innate response in these processes.<\/jats:p>","DOI":"10.1128\/jvi.02383-08","type":"journal-article","created":{"date-parts":[[2009,2,19]],"date-time":"2009-02-19T01:54:18Z","timestamp":1235008458000},"page":"4275-4286","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Replicon Particles of Venezuelan Equine Encephalitis Virus as a Reductionist Murine Model for Encephalitis"],"prefix":"10.1128","volume":"83","author":[{"given":"Alexandra","family":"Scha\u0308fer","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Carolina Vaccine Institute, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan C.","family":"Whitmore","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Carolina Vaccine Institute, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Konopka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Carolina Vaccine Institute, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1824"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/35094583"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.1106"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:NERE.0000021246.96864.89"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2000.0241"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1343"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.10.6760"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.8.3905-3908.2000"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00441.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.1197"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2001.0878"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.8.4585"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602460103"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00114-5"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701252104"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(94)90247-X"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.4.2717"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"4309","DOI":"10.4049\/jimmunol.154.9.4309","volume":"154","year":"1995","unstructured":"Ford, A. 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