Bovine herpesvirus 1 regulatory proteins bICP0 and VP16 are readily detected in trigeminal ganglionic neurons expressing the glucocorticoid receptor during the early stages of reactivation from latency.
Bovine herpesvirus 1 (BHV-1) establishes a lifelong latent infection in sensory neurons following acute infection. Increased corticosteroid levels, due to stress, increases the incidence of reactivation from latency. Within minutes, corticosteroids activate the glucocorticoid receptor and transcription of promoters containing a glucocorticoid receptor element. A single intravenous injection of the synthetic corticosteroid dexamethasone consistently induces reactivation from latency in calves. Lytic cycle viral gene expression is detected within 6 h after dexamethasone treatment of calves latently infected with BHV-1. Cellular transcription factors are induced by dexamethasone in trigeminal ganglionic neurons within 1.5 h after dexamethasone treatment, suggesting they promote viral gene expression during the early phases of reactivation from latency, which we operationally defined as the escape from latency. In this study, immunohistochemistry was utilized to examine viral protein expression during the escape from latency. Within 1.5 h after dexamethasone treatment, bICP0 and a late protein (VP16) were consistently detected in a subset of trigeminal ganglionic neurons. Most neurons expressing bICP0 also expressed VP16. Additional studies revealed that neurons expressing the glucocorticoid receptor also expressed bICP0 or VP16 at 1.5 h after dexamethasone treatment. Two other late proteins, glycoprotein C and D, were not detected until 6 h after dexamethasone treatment and were detected in only a few neurons. These studies provide evidence that VP16 and the promiscuous viral trans-activator (bICP0) are expressed during the escape from latency, suggesting they promote the production of infectious virus in a small subset of latently infected neurons.
School of Veterinary Medicine and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Morisson Life Science Center, Lincoln, Nebraska, USA.
Leticia
L
Frizzo da Silva
Insun
I
Kook
Alan
A
Doster
Clinton
C
Jones
D000818:Animals; D002417:Cattle; D003907:Dexamethasone / Q000008:administration & dosage; D045888:Ganglion Cysts / Q000821:virology*; D020869:Gene Expression Profiling; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism*; D007242:Herpesvirus 1, Bovine / Q000502:physiology*; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000008:administration & dosage; D009474:Neurons / Q000821:virology*; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014775:Virus Activation
D017405:Herpes Simplex Virus Protein Vmw65; D007155:Immunologic Factors; D011965:Receptors, Glucocorticoid; D015534:Trans-Activators; D003907:Dexamethasone; D044767:Ubiquitin-Protein Ligases; C086729:bICP0 protein, Bovine herpesvirus 1