title: Temperature and density dependent induction of a cytopathic effect following infection with non-cytopathic HAV strains.
abstract: Hepatitis A virus infection and growth in cultured cells is protracted, cell-type restricted, and generally not accompanied by the appearance of a cytopathic effect, with the exception of some culture-adapted strains. We demonstrate that the non-cytopathic HAV strain HM175/clone 1 can be induced to exhibit a cytopathic phenotype in both persistently or acutely infected cells under co-dependent conditions of lower incubation temperature (<34°C) and reduced cell density in both monkey (FRhK-4) and human (A549) cells. This phenotype is not virus-strain restricted, as it was also observed in cells infected with HAV strains, HAS-15 and LSH/S. Cytopathic effect was accompanied by rRNA cleavage, indicating activation of the RNase L pathway, viral negative strand synthesis, caspase-3 activation, and apoptosis. The results indicate that a cytopathic phenotype may be present in some HAV strains that can be induced under appropriate conditions, suggesting the potential for development of a plaque assay for this virus.
authors.affiliation: Division of Molecular Biology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, 8301 Muirkirk Road, Laurel, MD 20708, USA. samantha.wales@fda.hhs.gov
authors.forename: Samantha Q
authors.initials: SQ
authors.lastname: Wales
authors.forename: Diana
authors.initials: D
authors.lastname: Ngo
authors.forename: Kaoru
authors.initials: K
authors.lastname: Hida
authors.forename: Michael
authors.initials: M
authors.lastname: Kulka
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000528:radiation effects*; D004722:Endoribonucleases / Q000378:metabolism; D030041:Hepatitis A virus / Q000472:pathogenicity* / Q000528:radiation effects*; D006801:Humans; D008253:Macaca mulatta; D012335:RNA, Ribosomal / Q000378:metabolism; D013696:Temperature
chemical_list: D012335:RNA, Ribosomal; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease