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Analysis of bovine tonsils and trigeminal ganglia following infection with bovine herpesvirus type 1 (BHV-1) or a BHV-1 latency-related mutant strain

Sandra Elizabeth Perez de Bretschneider, University of Nebraska - Lincoln

Abstract

Bovine herpesvirus type 1 (BHV-1) is a pathogen of cattle that establishes latency primarily in trigeminal ganglia (TG). The latency-related (LR) gene is abundantly expressed at this stage. Reactivation from latency can occur by dexamethasone (DEX) treatment. To study the role of the LR gene, a BHV-1 mutant virus (LR mutant) that does not express LR protein products was constructed (Inman et al., 2001). The role of the LR gene in BHV-1 infection was examined in tonsils. The LR mutant and wild type (wt) BHV-1 established latency in the tonsils. The LR gene promoted virus growth and in vivo reactivation from latency in tonsils. Expression of the immediate-early gene bICP0 correlated with the early events of reactivation. In LR mutant-infected tissues, reactivation was blocked downstream of bICP0 RNA expression. Down-regulation of LR protein expression appeared to facilitate bICPO. It was concluded that the LR gene was, in part, responsible for the different outcomes of infection in neuronal and lymphoid cells. Compared to wt BHV-1, the LR mutant stimulated a stronger innate response in peripheral tissues after acute infection. Furthermore, beta interferon RNA expression was higher in tonsils, and occurred earlier in bovine cells following infection with the LR mutant. Expression of the IFN-γ-receptor was exclusively detected in TG of calves latently infected with wt BHV-1, suggesting that the virus was capable of spontaneous molecular reactivation that stimulated infiltrating cells to produce the cytokine. By laser capture microdissection, I determined that neurons surrounded by mononuclear cells are infected with BHV-1. The number of infected neurons and the pattern of migration of inflammatory cells correlated with the capability of the LR mutant to replicate in TG. Finally, immunohistochemical studies demonstrated that proteins encoded by the LR gene and the novel ORF-E transcript are expressed in TG. Collectively, these studies suggested that the LR protein has functions associated with the prevention of antiviral immune mechanisms.

Subject Area

Veterinary services|Animal diseases|Microbiology

Recommended Citation

Perez de Bretschneider, Sandra Elizabeth, "Analysis of bovine tonsils and trigeminal ganglia following infection with bovine herpesvirus type 1 (BHV-1) or a BHV-1 latency-related mutant strain" (2006). ETD collection for University of Nebraska-Lincoln. AAI3209276.
https://digitalcommons.unl.edu/dissertations/AAI3209276

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