{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:54:48Z","timestamp":1791262488458,"version":"4.1.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The severity of West Nile virus (WNV) infection in immunocompetent animals is highly strain dependent, ranging from avirulent to highly neuropathogenic. Here, we investigate the nature of this strain-specific restriction by analyzing the replication of avirulent (WNV-MAD78) and highly virulent (WNV-NY) strains in neurons, astrocytes, and microvascular endothelial cells, which comprise the neurovascular unit within the central nervous system (CNS). We demonstrate that WNV-MAD78 replicated in and traversed brain microvascular endothelial cells as efficiently as WNV-NY. Likewise, similar levels of replication were detected in neurons. Thus, WNV-MAD78's nonneuropathogenic phenotype is not due to an intrinsic inability to replicate in key target cells within the CNS. In contrast, replication of WNV-MAD78 was delayed and reduced compared to that of WNV-NY in astrocytes. The reduced susceptibility of astrocytes to WNV-MAD78 was due to a delay in viral genome replication and an interferon-independent reduction in cell-to-cell spread. Together, our data suggest that astrocytes regulate WNV spread within the CNS and therefore are an attractive target for ameliorating WNV-induced neuropathology.<\/jats:p>","DOI":"10.1128\/jvi.02577-12","type":"journal-article","created":{"date-parts":[[2012,12,26]],"date-time":"2012-12-26T20:35:08Z","timestamp":1356554108000},"page":"2814-2822","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Differential Replication of Pathogenic and Nonpathogenic Strains of West Nile Virus within Astrocytes"],"prefix":"10.1128","volume":"87","author":[{"given":"Katherine L.","family":"Hussmann","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland College Park, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie A.","family":"Samuel","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Molecular Microbiology, and Pathology &amp; Immunology, Washington University, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang S.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Molecular Microbiology, and Pathology &amp; Immunology, Washington University, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda L.","family":"Fredericksen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland College Park, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1705.101759"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","unstructured":"PapaA\nDanisK\nBakaA\nBakasA\nDougasG\nLytrasT\nTheocharopoulosG\nChrysagisD\nVassiliadouE\nKamariaF\nLionaA\nMellouK\nSaroglouG\nPanagiotopoulosT. 2010. 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