title: Bovine herpesvirus type 1 induces cell death by a cell-type-dependent fashion.
abstract: Bovine herpesvirus 1 (BHV-1), a member of the alpha-herpesvirinae sub-family, causes significant losses to the cattle industry. BHV-1 establishes latency in trigeminal ganglionic sensory neurons, but periodically reactivates from latency. Previous studies suggested that infection with BHV-1-induced novel morphological changes in rabbit skin (RS) cells versus bovine kidney cells (MDBK). Consequently, we hypothesized that viral infection led to a novel form of cell death in RS cells compared to MDBK cells. To test this hypothesis, we examined the levels of apoptosis in these cell types following infection with BHV-1. Infection of RS, but not MDBK, cells leads to high levels of apoptosis compared to mock-infected cells. Previous studies indicated that a BHV-1 recombinant virus that does not express the bICP0 protein grows poorly in permissive cells and induces a persistent-like infection. This suggested that bICP0 played an important role in regulating cell death following infection. To test this hypothesis, we compared the levels of apoptosis in cells infected with the bICP0 null mutant versus viral strains that expressed bICP0. The bICP0 null mutant induces low levels of apoptosis in RS or MDBK cells. When MDBK cells are treated with UV light prior to infection, bICP0 expressing viral strains, but not the bICP0 null mutant, inhibited UV-induced apoptosis. Infection of MDBK cells with the bICP0 null mutant, leads to an accumulation of autophagosomes that are not detected following infection with bICP0 expressing viruses. These studies suggest that the bICP0 null mutant induces autophagy in MDBK cells, and bICP0 protein expression mediates cell-type specific cytotoxicity.
authors.affiliation: Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, NE 68583, USA.
authors.forename: Vicki
authors.initials: V
authors.lastname: Geiser
authors.forename: Suzanne
authors.initials: S
authors.lastname: Rose
authors.forename: Clinton
authors.initials: C
authors.lastname: Jones
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000821:virology; D016923:Cell Death / Q000528:radiation effects; D002460:Cell Line; D053938:DNA Fragmentation; D006566:Herpesviridae Infections / Q000503:physiopathology* / Q000821:virology; D007242:Herpesvirus 1, Bovine / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D046529:Microscopy, Electron, Transmission; D011817:Rabbits; D013045:Species Specificity; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D015534:Trans-Activators; D044767:Ubiquitin-Protein Ligases; C086729:bICP0 protein, Bovine herpesvirus 1