{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:32:34Z","timestamp":1760121154542},"reference-count":37,"publisher":"Microbiology Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,6,1]]},"abstract":"<jats:p>Coxsackievirus B (CVB) is often associated with aseptic meningitis and encephalitis, but the six serotypes of CVB vary in their relative disease severity. To elucidate the detailed mechanisms of CVB-induced cytopathological effects, the morphological and biochemical characteristics caused by the CVB serotypes in mouse primary cortical neuronal cells were investigated. By 24\u2005h post-infection, all CVB serotypes except CVB2 induced severe cytotoxic alterations, including a loss of neurites. Both fluorescence and transmission electron microscopy revealed CVB-induced morphological changes indicative of apoptosis, including heavily condensed nuclei, subsequent chromatin condensation into the periphery of the nuclei and oligonucleosomal DNA fragmentation. It was also found that infection with all six CVB serotypes led to productive virus replication, which was completed prior to an apoptotic signal. The caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone significantly inhibited nuclear changes associated with virus-induced apoptosis, but had less effect on virus-associated cytopathic effects and no effect on virus production. In contrast, the transcription inhibitor actinomycin D profoundly inhibited all three virus-induced events. Taken together, these findings demonstrate that all six CVB serotypes can efficiently replicate in mouse cortical neuronal cells and that productive replication of these CVBs, except for CVB2, induces multiple cytopathological effects, including apoptotic alterations.<\/jats:p>","DOI":"10.1099\/vir.0.19695-0","type":"journal-article","created":{"date-parts":[[2004,5,27]],"date-time":"2004-05-27T20:48:15Z","timestamp":1085690895000},"page":"1555-1564","source":"Crossref","is-referenced-by-count":15,"title":["Susceptibility of mouse primary cortical neuronal cells to coxsackievirus B"],"prefix":"10.1099","volume":"85","author":[{"given":"Jeonghyun","family":"Ahn","sequence":"first","affiliation":[{"name":"Departments of Microbiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jene","family":"Choi","sequence":"additional","affiliation":[{"name":"Departments of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chul Hyun","family":"Joo","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilseon","family":"Seo","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DongHou","family":"Kim","sequence":"additional","affiliation":[{"name":"Departments of Anatomy and Cell Biology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Yong","family":"Yoon","sequence":"additional","affiliation":[{"name":"Departments of Anatomy and Cell Biology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoo Kyum","family":"Kim","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heuiran","family":"Lee","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1006\/viro.1998.9438","article-title":"Two types of death of poliovirus-infected cells: caspase involvement in the apoptosis but not cytopathic effect","volume":"252","author":"Agol","year":"1998","journal-title":"Virology"},{"key":"R2","doi-asserted-by":"crossref","first-page":"5534","DOI":"10.1128\/JVI.74.12.5534-5541.2000","article-title":"Competing death programs in poliovirus-infected cells: commitment switch in the middle of the infectious cycle","volume":"74","author":"Agol","year":"2000","journal-title":"J Virol"},{"key":"R3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1159\/000072435","article-title":"Characteristics of apoptotic cell death induced by coxsackievirus B in Vero cells","volume":"46","author":"Ahn","year":"2003","journal-title":"Intervirology"},{"key":"R4","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S0166-2236(00)01591-5","article-title":"Altruistic cell suicide and the specialized case of the virus-infected nervous system","volume":"23","author":"Allsopp","year":"2000","journal-title":"Trends Neurosci"},{"key":"R5","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/sj.cdd.4400298","article-title":"Virus infection induces neuronal apoptosis: a comparison with trophic factor withdrawal","volume":"5","author":"Allsopp","year":"1998","journal-title":"Cell Death Differ"},{"key":"R6","doi-asserted-by":"crossref","first-page":"7669","DOI":"10.1128\/JVI.72.9.7669-7675.1998","article-title":"Caspase activation and specific cleavage of substrates after coxsackievirus B3-induced cytopathic effect in HeLa cells","volume":"72","author":"Carthy","year":"1998","journal-title":"J Virol"},{"key":"R7","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1099\/0022-1317-83-8-1925","article-title":"An ex vivo murine model to study poliovirus-induced apoptosis in nerve cells","volume":"83","author":"Couderc","year":"2002","journal-title":"J Gen Virol"},{"key":"R8","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1101\/gad.12.11.1551","article-title":"Proteases to die for","volume":"12","author":"Cryns","year":"1998","journal-title":"Genes Dev"},{"key":"R9","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1177\/106002808301700707","article-title":"Reactions and interactions in handling anticancer drugs","volume":"17","author":"D'Arcy","year":"1983","journal-title":"Drug Intell Clin Pharm"},{"key":"R10","first-page":"9","article-title":"Coxsackie B2 virus isolation from a case of postnatal meningoencephalitis","volume":"31","author":"Draganescu","year":"1980","journal-title":"Virologie"},{"key":"R11","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1146\/annurev.biochem.68.1.383","article-title":"Mammalian caspases: structure, activation, substrates, and functions during apoptosis","volume":"68","author":"Earnshaw","year":"1999","journal-title":"Annu Rev Biochem"},{"key":"R12","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0168-1702(02)00049-7","article-title":"Vesicular stomatitis virus induces apoptosis at early stages in the viral cycle and does not depend on virus replication","volume":"86","author":"Gadaleta","year":"2002","journal-title":"Virus Res"},{"key":"R13","doi-asserted-by":"crossref","first-page":"6066","DOI":"10.1128\/JVI.73.7.6066-6072.1999","article-title":"Poliovirus induces apoptosis in the mouse central nervous system","volume":"73","author":"Girard","year":"1999","journal-title":"J Virol"},{"key":"R14","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0966-842X(99)01470-5","article-title":"Perspective: virus infections and the death of neurons","volume":"7","author":"Griffin","year":"1999","journal-title":"Trends Microbiol"},{"key":"R15","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1099\/0022-1317-83-7-1547","article-title":"A time to kill: viral manipulation of the cell death program","volume":"83","author":"Hay","year":"2002","journal-title":"J Gen Virol"},{"key":"R16","first-page":"3","article-title":"Historical background","volume-title":"In Viral Infections of the Nervous System","author":"Johnson","year":"1998a"},{"key":"R17","first-page":"87","article-title":"Meningigis, encephalitis, and poliomyelitis","volume-title":"In Viral Infections of the Nervous System","author":"Johnson","year":"1998b"},{"key":"R18","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0304-3940(02)00340-3","article-title":"Coxsackievirus B4-induced neuronal apoptosis in rat cortical cultures","volume":"326","author":"Joo","year":"2002","journal-title":"Neurosci Lett"},{"key":"R19","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/S1286-4579(00)01265-X","article-title":"Physiological significance of apoptosis in animal virus infection","volume":"2","author":"Koyama","year":"2000","journal-title":"Microbes Infect"},{"key":"R20","first-page":"527","article-title":"Influenza virus overcomes apoptosis by rapid multiplication","volume":"3","author":"Kurokawa","year":"1999","journal-title":"Int J Mol Med"},{"key":"R21","first-page":"20","article-title":"Growth, assay and purification of picornaviruses","volume-title":"In Virology: a Practical Approach","author":"Minor","year":"1996"},{"key":"R22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J Immunol Methods"},{"key":"R23","first-page":"258","article-title":"Enteroviruses and heart disease","volume":"50","author":"Muir","year":"1993","journal-title":"Br J Biomed Sci"},{"key":"R24","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1097\/00008480-200102000-00017","article-title":"What's new with enteroviral infections?","volume":"13","author":"Nigrovic","year":"2001","journal-title":"Curr Opin Pediatr"},{"key":"R25","doi-asserted-by":"crossref","first-page":"S479","DOI":"10.1016\/S0002-8703(99)70280-2","article-title":"Enteroviruses and myocardial infarction","volume":"138","author":"Roivainen","year":"1999","journal-title":"Am Heart J"},{"key":"R26","first-page":"432","article-title":"Mechanisms of coxsackievirus-induced damage to human pancreatic beta-cells","volume":"85","author":"Roivainen","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"R27","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1093\/clinids\/20.4.971","article-title":"Enteroviral infections of the central nervous system","volume":"20","author":"Rotbart","year":"1995a","journal-title":"Clin Infect Dis"},{"key":"R28","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1128\/9781555818326","article-title":"Meningitis and encephalitis","volume-title":"In Human Enterovirus Infections","author":"Rotbart","year":"1995b"},{"key":"R29","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1128\/9781555818326","article-title":"Laboratory diagnosis of enteroviral infections","volume-title":"In Human Enterovirus Infections","author":"Rotbart","year":"1995"},{"key":"R30","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1146\/annurev.micro.53.1.577","article-title":"Viruses and apoptosis","volume":"53","author":"Roulston","year":"1999","journal-title":"Annu Rev Microbiol"},{"key":"R31","first-page":"609","article-title":"Picornaviridae: the viruses and their replication","volume-title":"In Fields Virology","author":"Rueckert","year":"1996"},{"key":"R32","doi-asserted-by":"crossref","first-page":"20003","DOI":"10.1074\/jbc.272.32.20003","article-title":"Cell density-dependent apoptosis in HL-60 cells, which is mediated by an unknown soluble factor, is inhibited by transforming growth factor beta1 and overexpression of Bcl-2","volume":"272","author":"Saeki","year":"1997","journal-title":"J Biol Chem"},{"key":"R33","first-page":"133","article-title":"Apoptosis: the biochemistry and molecular biology of programmed cell death","volume":"14","author":"Schwartzman","year":"1993","journal-title":"Endocr Rev"},{"key":"R34","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1042\/bj3150021","article-title":"Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32","volume":"315","author":"Slee","year":"1996","journal-title":"Biochem J"},{"key":"R35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/gad.10.1.1","article-title":"Life, death, and the pursuit of apoptosis","volume":"10","author":"White","year":"1996","journal-title":"Genes Dev"},{"key":"R36","first-page":"373","article-title":"Detection of viral aetiology in cerebral spinal fluid samples from 580 clinical cases","volume":"14","author":"Xie","year":"2000","journal-title":"Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi"},{"key":"R37","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1542\/pir.19-6-183","article-title":"Enterovirus infections","volume":"19","author":"Zaoutis","year":"1998","journal-title":"Pediatr Rev"}],"container-title":["Journal of General Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.19695-0?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T15:40:19Z","timestamp":1601998819000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.19695-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6,1]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2004,6,1]]}},"URL":"https:\/\/doi.org\/10.1099\/vir.0.19695-0","relation":{},"ISSN":["0022-1317","1465-2099"],"issn-type":[{"value":"0022-1317","type":"print"},{"value":"1465-2099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,6,1]]}}}