APOPTOSIS AND HOST-DEFENSE PEPTIDE CATHELICIDINS DETERMINE DIFFERENT OUTCOMES OF BOVINE ALPHA-HERPESVIRUSES NEUROPATHOGENESIS

RENSETTI D; PÉREZ, S.; BURUCÚA M; QUINTANA S,; MARIN M; ODEÓN A,

París

Congreso; 26th Biennial Meeting of the International Society for Neurochemistry and the European Society for Neurochemistry; 2017

International Society for Neurochemistry (ISN) and European Society for Neurochemistry (ESN)

Alpha-herpesvirusesare closely related virusesthat cause neuro¬logical dis¬ease 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). Antimicro¬bial cathelicidin peptides modulateTLR4 ex¬pression in epithelial cells although their func¬tion in the nervous system remains elusive. These innate factors together with spe¬ci¬fic BoHV-apoptotic po¬tential could be determinant in the neuro¬patho¬genesis as they could pro-mote or limit the in¬flam¬matory re¬sponse. In this study, we determined apoptosis and the ex-pression 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 ganglio¬n (TG)were col¬lected for immuno¬cyto¬chemical detection of cleaved caspase 3 and messenger gene determination of bovine cathelicidins BMAP27 and BMAP28 (RT-qPCR). At 6 dpi, caspase 3-apoptotic neu¬rons were detected in the TG of BoHV-1-infected calves, whereas fewer numbers of caspase 3 positive neu¬rons were ob¬served 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 sug¬gest that modulation of apoptosis and cathelicidin expression orchestrate the final in-flam¬matory outcomes of alpha-herpesviruses infection of the nervous system. Inhibition of both factorsmight be responsible for neuro¬logical lesionsin BoHV-5 infection. Further research will be required to determine the role of cathelicidins during infectious dis¬eases of the CNS.