title: Experimental Adaptation of Rotaviruses to Tumor Cell Lines.
abstract: A number of viruses show a naturally extended tropism for tumor cells whereas other viruses have been genetically modified or adapted to infect tumor cells. Oncolytic viruses have become a promising tool for treating some cancers by inducing cell lysis or immune response to tumor cells. In the present work, rotavirus strains TRF-41 (G5) (porcine), RRV (G3) (simian), UK (G6-P5) (bovine), Ym (G11-P9) (porcine), ECwt (murine), Wa (G1-P8), Wi61 (G9) and M69 (G8) (human), and five wild-type human rotavirus isolates were passaged multiple times in different human tumor cell lines and then combined in five different ways before additional multiple passages in tumor cell lines. Cell death caused by the tumor cell-adapted isolates was characterized using Hoechst, propidium iodide, 7-AAD, Annexin V, TUNEL, and anti-poly-(ADP ribose) polymerase (PARP) and -phospho-histone H2A.X antibodies. Multiple passages of the combined rotaviruses in tumor cell lines led to a successful infection of these cells, suggesting a gain-of-function by the acquisition of greater infectious capacity as compared with that of the parental rotaviruses. The electropherotype profiles suggest that unique tumor cell-adapted isolates were derived from reassortment of parental rotaviruses. Infection produced by such rotavirus isolates induced chromatin modifications compatible with apoptotic cell death.
authors.affiliation: Department of Physiological Sciences, Faculty of Medicine, Universidad Nacional de Colombia, Bogota, D.C., Colombia.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guerrero
authors.affiliation: Department of Physiological Sciences, Faculty of Medicine, Universidad Nacional de Colombia, Bogota, D.C., Colombia.
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Guerrero
authors.affiliation: Department of Physiological Sciences, Faculty of Medicine, Universidad Nacional de Colombia, Bogota, D.C., Colombia.
authors.forename: Elver
authors.initials: E
authors.lastname: Silva
authors.affiliation: Department of Physiological Sciences, Faculty of Medicine, Universidad Nacional de Colombia, Bogota, D.C., Colombia.
authors.forename: Orlando
authors.initials: O
authors.lastname: Acosta
authors.affiliation: Institute of Biotechnology, Universidad Nacional de Colombia, Bogota, D.C., Colombia.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Barreto
mesh_terms: D000222:Adaptation, Physiological; D000956:Antigens, Viral / Q000276:immunology; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002470:Cell Survival; D003588:Cytopathogenic Effect, Viral; D053903:DNA Breaks, Double-Stranded; D053938:DNA Fragmentation; D004260:DNA Repair; D004587:Electrophoresis, Agar Gel; D006657:Histones / Q000378:metabolism; D006801:Humans; D012401:Rotavirus / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D012400:Rotavirus Infections / Q000821:virology; D013997:Time Factors; D014771:Virion / Q000472:pathogenicity
chemical_list: D000956:Antigens, Viral; C468783:H2AX protein, human; D006657:Histones
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