{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:34:56Z","timestamp":1793313296959,"version":"4.5.0"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"20","license":[{"start":{"date-parts":[[2010,10,15]],"date-time":"2010-10-15T00:00:00Z","timestamp":1287100800000},"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":[[2010,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Polyomavirus JC (JCV) infects \u223c60% of the general population, followed by asymptomatic urinary shedding in \u223c20%. In patients with pronounced immunodeficiency, including HIV\/AIDS, JCV can cause progressive multifocal leukoencephalopathy (PML), a devastating brain disease of high mortality. While JCV in the urine of healthy people has a linear noncoding control region called the archetype NCCR (\n                    <jats:italic>at<\/jats:italic>\n                    -NCCR), JCV in brain and cerebrospinal fluid (CSF) of PML patients bear rearranged NCCRs (\n                    <jats:italic>rr<\/jats:italic>\n                    -NCCRs). Although JCV NCCR rearrangements are deemed pathognomonic for PML, their role as a viral determinant is unclear. We sequenced JCV NCCRs found in CSF of eight HIV\/AIDS patients newly diagnosed with PML and analyzed their effect on early and late gene expression using a bidirectional reporter vector recapitulating the circular polyomavirus early and late gene organization. The\n                    <jats:italic>rr<\/jats:italic>\n                    -NCCR sequences were highly diverse, but all increased viral early reporter gene expression in progenitor-derived astrocytes, glia-derived cells, and human kidney compared to the expression levels with the\n                    <jats:italic>at<\/jats:italic>\n                    -NCCR. The expression of simian virus 40 (SV40) large T antigen or HIV Tat expression in\n                    <jats:italic>trans<\/jats:italic>\n                    was associated with a strong increase of\n                    <jats:italic>at<\/jats:italic>\n                    -NCCR-controlled early gene expression, while\n                    <jats:italic>rr<\/jats:italic>\n                    -NCCRs were less responsive. The insertion of\n                    <jats:italic>rr-<\/jats:italic>\n                    NCCRs into the JCV genome backbone revealed higher viral replication rates for\n                    <jats:italic>rr<\/jats:italic>\n                    -NCCR compared to those of the\n                    <jats:italic>at<\/jats:italic>\n                    -NCCR JCV in human progenitor-derived astrocytes or glia cells, which was abrogated in SV40 large T-expressing COS-7 cells. We conclude that naturally occurring JCV\n                    <jats:italic>rr<\/jats:italic>\n                    -NCCR variants from PML patients confer increased early gene expression and higher replication rates compared to those of\n                    <jats:italic>at-<\/jats:italic>\n                    NCCR JCV and thereby increase cytopathology.\n                  <\/jats:p>","DOI":"10.1128\/jvi.00614-10","type":"journal-article","created":{"date-parts":[[2010,8,4]],"date-time":"2010-08-04T23:53:47Z","timestamp":1280966027000},"page":"10448-10456","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":131,"title":["Rearranged JC Virus Noncoding Control Regions Found in Progressive Multifocal Leukoencephalopathy Patient Samples Increase Virus Early Gene Expression and Replication Rate"],"prefix":"10.1128","volume":"84","author":[{"given":"Rainer","family":"Gosert","sequence":"first","affiliation":[{"name":"Transplantation Virology, Institute for Medical Microbiology, Department of Biomedicine, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Kardas","sequence":"additional","affiliation":[{"name":"Transplantation Virology, Institute for Medical Microbiology, Department of Biomedicine, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene O.","family":"Major","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans H.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Transplantation Virology, Institute for Medical Microbiology, Department of Biomedicine, University of Basel, Basel, Switzerland"},{"name":"Infectious Diseases &amp; Hospital Epidemiology, University Hospital Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-78-3-659"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199810000-00006"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/81.1.93"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-74-8-1499"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-107-1-78"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.MP.0000044622.04245.A9"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/427698"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/13550280390195298"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1080\/13550280152537247"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.22.10881"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.0037"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/13550280590900382"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32830a5043"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000269706.59977.a5"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000194804.97164.86"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/13550280390195315"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh215"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.18.10206-10210.2004"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2006.04.003"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1086\/597126"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.51.2.458-469.1984"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2008.02402.x"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1086\/313598"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072097"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1086\/383034"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.1998.tb00040.x"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(03)00770-9"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(89)90359-4"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.3.4.629"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198802043180507"},{"key":"e_1_3_2_32_2","first-page":"2263","year":"2007","unstructured":"Imperiale, M. 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