Experimental reactivation of bovine herpesvirus 1 (BHV-1) by means of corticosteroids in an intranasal rabbit model

Abstract

Intranasal inoculation of the rabbit was shown to be a viable alternative to eye inoculation as a model to study latency and reactivation of bovine herpesvirus 1 (BHV-1). In four different experiments, separate groups of rabbits were intranasally inoculated with BHV-1. In two experiments some rabbits were inoculated instead with a TK-defective (TK-) mutant strain of BHV-1. The development of a specific antibody response was monitored by both virus neutralization and ELISA assays. Cell-mediated immunity was measured by means of a skin test. Many weeks after virus inoculation the rabbits were treated with corticosteroid. Antibody formation after treatment was markedly different in wild type and in TK- virus inoculated groups. In the former, virus reactivation was suggested by a sudden rise in serum antibody levels with kinetics closely resembling those reported in infected calves following corticosteroid administration, whereas in the case of the TK- group no significant increase in antibody activity was measured. Histopathological changes in trigeminal ganglia also indicated reactivation of virus in the wild-type virus infected animals. Further evidence for reactivation was obtained by virus isolation from nasal swabs after corticosteroid treatment.

A Protein Encoded by the Bovine Herpesvirus 1 Latency-Related Gene Interacts with Specific Cellular Regulatory Proteins, Including CCAAT Enhancer Binding Protein Alpha

“…If PC12 cells or primary sympathetic neurons are deprived of nerve growth factor, Cdc42 is activated, resulting in apoptosis (39,68). Since DEX reproducibly induces BHV-1 reactivation from latency (1,2,7,26,37,54,58,66) and DEX is a potent stressor, Cdc42 may be activated in TG.…”

Cellular Transcription Factors Induced in Trigeminal Ganglia during Dexamethasone-Induced Reactivation from Latency Stimulate Bovine Herpesvirus 1 Productive Infection and Certain Viral Promoters

“…DEX reproducibly induces reactivation from latency, as judged by virus shedding from ocular or nasal cavities (1,8,24,27,37,40,68,75,87,88). Six hours after DEX treatment viral transcripts are detected in a subset of TG neurons by in situ hybridization using a probe that hybridizes to ribonucleotide reductase, glycoprotein C, and ICP4 (68,87,89).…”

Open Reading Frame 2, Encoded by the Latency-Related Gene of Bovine Herpesvirus 1, Has Antiapoptotic Activity in Transiently Transfected Neuroblastoma Cells

“…Neuronal stress, including the removal of nerve growth factor from neuronal cultures (31,52), induces the activity of Cdc42, a Rho GTPase family member, and apoptosis (17,31,52). Dexamethasone is a potent stressor and induces reactivation from latency (1,2,6,19,29,42,46,50), suggesting that Cdc42 is activated in TG. It will be of interest to test whether ORF-2 alone interacts with Bid or Cdc42.…”