Modulation of granzymes mRNA expression in neural tissue of BoAHV-1 and BoAHV-5-infected cattle

Bovine alphaherpesviruses (BoAHV)-1 and 5 are neurotropic viruses of cattle which differ in their neuropathogenic potential. BoAHV-5 is responsible for non-suppurative meningoencephalitis in calves while BoAHV-1 can occasionally cause encephalitis. Granzymes (GZMs) are serine-proteases that participate in CD8⁺ T cells-mediated killing of virally-infected cells upon release through perforin (PFN)-formed pores in the cell membrane. Recently, six GZMs have been identified in cattle (A, B, K, H, M and O). However, their expression in bovine tissues has not been evaluated. In this study, the mRNA expression levels of PFN and GZMs A, B, K, H and M in the nervous system of calves experimentally-inoculated with BoAHV-1 or BoAHV-5 were analyzed at the three distinct stages of the infectious cycle of alphaherpesviruses: acute infection, latency and reactivation. This is the first report describing the expression of GZMs in bovine neural tissue and the first analysis of GZM expression in the context of bovine alphaherpesviruses neuropathogenesis. The findings revealed that PFN and GZM K are upregulated during BoAHV-1 or BoAHV-5 acute infection. In contrast to BoAHV-1, during BoAHV-5 latency a significant up-regulation of PFN, GZM K and GZM H was detected. PFN and GZM A, K and H expression was also up-regulated during BoAHV-5 reactivation. Therefore, a distinct pattern of PFN and GZM expression is evident along the infectious cycle of each alphaherpesvirus and this might contribute to the differences in BoAHV-1 and BoAHV-5 neuropathogenesis.