title: Bovine herpesvirus 1 can efficiently infect the human (SH-SY5Y) but not the mouse neuroblastoma cell line (Neuro-2A).
abstract: Bovine herpesvirus 1 (BoHV-1) is a significant bovine pathogen that establishes a life-long latent infection in sensory neurons. Previous attempts to develop immortalized bovine neuronal cells were unsuccessful. Consequently, our understanding of the BoHV-1 latency-reactivation cycle has relied on studying complex virus-host interactions in calves. In this study, we tested whether BoHV-1 can infect human (SH-SY5Y) or mouse (Neuro-2A) neuroblastoma cells. We provide new evidence that BoHV-1 efficiently infects SH-SY5Y cells and yields virus titers approximately 100 fold less than bovine kidney cells. Conversely, virus titers from productively infected Neuro-2A cells were approximately 10,000 fold less than bovine kidney cells. Using a β-Gal expressing virus (gC-Blue), we demonstrate that infection of Neuro-2A cells (actively dividing or differentiated) does not result in efficient virus spread, unlike bovine kidney or SH-SY5Y cells. Additional studies demonstrated that lytic cycle viral gene expression (bICP4 and gE) was readily detected in SH-SY5Y cells: conversely bICP4 was not readily detected in productively infected Neuro-2A cells. Finally, infection of SH-SY5Y and bovine kidney cells, but not Neuro-2A cells, led to rapid activation of the Akt protein kinase. These studies suggest that the Neuro-2A cell line may be a novel cell culture model to identify factors that regulate BoHV-1 productive infection in neuronal cells.
authors.affiliation: Oklahoma State University, Center for Veterinary Health Sciences, Department of Veterinary Pathobiology, Stillwater, OK 74078, United States.
authors.forename: Prasanth
authors.initials: P
authors.lastname: Thunuguntla
authors.affiliation: Oklahoma State University, Center for Veterinary Health Sciences, Department of Veterinary Pathobiology, Stillwater, OK 74078, United States; Benha University, Faculty of Veterinary Medicine, Department of Virology, Moshtohor 13736, Kaliobyia, Egypt.
authors.forename: Fouad S
authors.initials: FS
authors.lastname: El-Mayet
authors.affiliation: Oklahoma State University, Center for Veterinary Health Sciences, Department of Veterinary Pathobiology, Stillwater, OK 74078, United States. Electronic address: clint.jones10@okstate.edu.
authors.forename: Clinton
authors.initials: C
authors.lastname: Jones
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007242:Herpesvirus 1, Bovine / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D058507:Host Specificity; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D017735:Virus Latency; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D014759:Viral Envelope Proteins; D014764:Viral Proteins; C046998:bovine herpesvirus type-1 glycoproteins; C083786:immediate early protein BICP4, bovine herpesvirus 1; D051057:Proto-Oncogene Proteins c-akt; D001616:beta-Galactosidase
keywords: Akt; Bovine herpesvirus 1 (BoHV-1); Neuroblastoma cells; Productive infection