{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:36:25Z","timestamp":1791333385595,"version":"4.3.1"},"reference-count":33,"publisher":"Microbiology Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,1,1]]},"abstract":"<jats:p>\n                    The polyomavirus JC (JCV) infects glial cells and causes progressive multifocal leukoencephalopathy (PML). We described a novel JCV-variant with a 10 bp deletion in the C terminus of the VP1 capsid protein, JCV\n                    <jats:sub>GCN1<\/jats:sub>\n                    . This mutant was associated with lytic infection of cerebellar granule cell neurons and cerebellar atrophy in an human immunodeficiency virus\/PML patient. This condition, also observed independently from PML, was named JCV granule cell neuronopathy (JCV GCN). We characterized JCV mutations in cerebrospinal fluid (CSF) of four other JCV GCN patients, and reviewed the literature on 10 reported cases. The strain from one patient harboured the identical GCN1-deletion, while the other patients had novel mutations in the same area, named JCV\n                    <jats:sub>GCN2\u20134<\/jats:sub>\n                    , causing variable changes in VP1 structure. One patient also had wild-type JCV in the CSF. To study the mechanisms leading to JCV GCN, we compared viral replication kinetics from JCV\n                    <jats:sub>GCN1<\/jats:sub>\n                    with the prototype JCV\n                    <jats:sub>Mad1<\/jats:sub>\n                    , the PML isolate JCV\n                    <jats:sub>HWM<\/jats:sub>\n                    and the prototype JCV\n                    <jats:sub>Mad1D<\/jats:sub>\n                    engineered with the GCN1-deletion. While all strains replicated at low levels in the medulloblastoma cell line DAOY from a cerebellar neuronal tumour, JCV\n                    <jats:sub>Mad1<\/jats:sub>\n                    replicated better in astroglial SVG cells than JCV\n                    <jats:sub>Mad1D<\/jats:sub>\n                    or JCV\n                    <jats:sub>GCN1<\/jats:sub>\n                    and all strains replicated at higher levels in COS-7 kidney cells, suggesting that the GCN1-deletion confers a disadvantage for viral growth in central nervous system white matter. The GCN1-deletion remained stable after 100 days in culture and VP1 protein was produced in all cell lines, indicating that JCV\n                    <jats:sub>GCN1<\/jats:sub>\n                    is replication-competent\n                    <jats:italic>in vitro<\/jats:italic>\n                    . These data highlight an important and previously overlooked aspect of JCV-pathogenesis. Detection of GCN-type JCV strains in CSF may help clinicians diagnose JCV GCN.\n                  <\/jats:p>","DOI":"10.1099\/vir.0.037440-0","type":"journal-article","created":{"date-parts":[[2011,9,22]],"date-time":"2011-09-22T20:43:12Z","timestamp":1316724192000},"page":"175-183","source":"Crossref","is-referenced-by-count":71,"title":["JC virus granule cell neuronopathy is associated with VP1 C terminus mutants"],"prefix":"10.1099","volume":"93","author":[{"given":"Xin","family":"Dang","sequence":"first","affiliation":[{"name":"Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA"},{"name":"Division of Neurovirology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose E.","family":"Vidal","sequence":"additional","affiliation":[{"name":"Department of Neurology, Emilio Ribas Institute of Infectious Disease, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto C.","family":"Penalva de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Neurology, Emilio Ribas Institute of Infectious Disease, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Departments of Neuroscience and Pathology, Mount Sinai School of Medicine, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Morgello","sequence":"additional","affiliation":[{"name":"Division of Neuropathology, Mount Sinai School of Medicine, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H.","family":"Hecht","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children's National Medical Center, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long H.","family":"Ngo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor J.","family":"Koralnik","sequence":"additional","affiliation":[{"name":"Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA"},{"name":"Division of Neurovirology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"r1","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1128\/JCM.27.6.1174-1179.1989","article-title":"Detection of BK virus and JC virus in urine and brain tissue by the polymerase chain reaction","volume":"27","author":"Arthur","year":"1989","journal-title":"J Clin Microbiol"},{"key":"r2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.7326\/0003-4819-107-1-78","article-title":"Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. 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