Apoptosis and host-defense peptide cathelicidins determine different outcomes of bovine Alpha-herpesviruses neuropathogenesis

Abstract

Alpha-herpesvirusesare closely related virusesthat cause neuro¬logical disease in humans and cattle. Bovine herpesvirus (BoHV) type 5 is an important cause of encephalitis in cattle. How-ever, encephalitis by BoHV-1 occurs occasionally. It is unknown how the innate immune re-sponse contri¬butes to their differences inneuro¬patho¬genesis. BoHV-5 spe¬ci¬fically induced the ex¬pression of Toll-like receptors (TLRs) in bovine neural inflamed tissue (Marin et al., 2014). Antimicrobial cathelicidin peptides modulateTLR4 expression in epithelial cells although their function in the nervous system remains elusive. These innate factors together with specific BoHV-apoptotic potential could be determinant in the neuropathogenesis as they could promote or limit the inflammatory response. In this study, we determined apoptosis and the expression of cathelicidins in thebovine nervous system during BoHV-1 and 5acute infections. Calves were inoculated with BoHV-1 Cooper or BoHV-5 97/613 strains (106.3 TCID50) or inert culture medium (control). At 6 days post-infection (dpi), different regions of central nervous system (CNS) and trigeminal ganglion (TG)were collected for immunocytochemical detection of cleaved caspase 3 and messenger gene determination of bovine cathelicidins BMAP27 and BMAP28 (RT-qPCR). At 6 dpi, caspase 3-apoptotic neurons were detected in the TG of BoHV-1-infected calves, whereas fewer numbers of caspase 3 positive neurons were observed in BoHV-5-infected calves. Cathelicidins expression was up- and down-regulated in CNS from BoHV-1- and BoHV-5-infected calves, respectively. BMAP27 was noticeably up-regulated in TG from BoHV-1-infected calves, while BMAP28 was only detected in BoHV-5-infected calves. Our find-ings suggest that modulation of apoptosis and cathelicidin expression orchestrate the final inflammatory outcomes of alpha-herpesviruses infection of the nervous system. Inhibition of both factorsmight be responsible for neurological lesionsin BoHV-5 infection. Further research will be required to determine the role of cathelicidins during infectious diseases of the CNS.