title: Susceptibility of mouse primary cortical neuronal cells to coxsackievirus B.
abstract: 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 h 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.
authors.affiliation: Departments of Microbiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea.
authors.forename: Jeonghyun
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Departments of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea.
authors.forename: Jene
authors.initials: J
authors.lastname: Choi
authors.affiliation: Departments of Microbiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea.
authors.forename: Chul Hyun
authors.initials: CH
authors.lastname: Joo
authors.affiliation: Departments of Microbiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea.
authors.forename: Ilseon
authors.initials: I
authors.lastname: Seo
authors.affiliation: Departments of Anatomy and Cell Biology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea.
authors.forename: DongHou
authors.initials: D
authors.lastname: Kim
authors.affiliation: Departments of Anatomy and Cell Biology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea.
authors.forename: Seung Yong
authors.initials: SY
authors.lastname: Yoon
authors.affiliation: Departments of Microbiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea.
authors.forename: Yoo Kyum
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Departments of Microbiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa, PO Box 145, Seoul, Korea.
authors.forename: Heuiran
authors.initials: H
authors.lastname: Lee
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002540:Cerebral Cortex / Q000821:virology*; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral; D003609:Dactinomycin / Q000494:pharmacology; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000821:virology*; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D000590:Amino Acid Chloromethyl Ketones; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D003609:Dactinomycin