2015; Winkler et al
2015; Winkler et al. in the olfactory bulbs (OB) of 16 cows suffering from acute BHV5-induced neurological disease. The OBs were analyzed for viral antigens and genome, miR-155 and TLR 3, 7, and 9 expression considering three major regions: olfactory receptor neurons (ORNs), glomerular layer (GL), and mitral cell layer (ML). BHV5 antigens and viral genomes, corresponding to gene, were detected in all OBs regions by fluorescent antibody assay (FA) and PCR, respectively. TLR 3, 7, and 9 transcripts were upregulated in ORNs and ML, yet only ORN layers revealed a positive correlation between TLR3 and miR-155 transcription. In ML, miR-155 correlated positively with all TLRs studied. Herein, our results evidence miR-155 transcription in BHV5 infected OB tissue associated to TLRs expression specifically ORNs which may be a new window for further studies. (Davison et al. 2009; Davison 2010). BHV5 is a neurotropic virus that produces neurological disease mainly in young animals worldwide, especially in South Phensuximide American countries (Vogel et al. 2003). Following primary replication in the nasal mucosa, BHV5 is believed to invade the central nervous system (CNS) mainly through the olfactory route (Vogel et al. 2003; Mori et al. 2004; Perez et al. 2006). The olfactory mucosa is composed by a neuroepithelium divided into layers organized initially by nasal mucosa, olfactory receptor neurons (ORNs), glomerular layer (GL), cribriforme plate, mitral cell layer (ML), and limbic system (Mori et al. 2004). The olfactory receptor neurons (ORNs) are bipolar neuronal cells whose axons leave the epithelium, penetrate the cribriform plate, enter the olfactory bulb and, finally, make synapse with the dendrites of mitral cells in the glomerular layer (Mori et al. 2004; Shivkumar et al. 2013). Mitral cells project to the olfactory and limbic systems, mainly the olfactory cortex and hippocampus, respectively (Mori et al. 2004; van Riel et Phensuximide al. 2015). During acute infection, BHV5 gains access mostly to the CNS cranial areas, indicating that viral invasion occurs more directly along olfactory neurons (Chowdhury et al. 1997; Favier et al. 2014). Despite evidences indicating that BHV5 uses the olfactory pathway Phensuximide to invade the CNS, detailed information on the sequential progression of the virusand the host-mediated immune eventsthrough the OB layers is lacking. Toll-like receptors (TLRs) are a broad family of conserved innate immune receptors that recognize pathogen-associated molecular patterns (PAMPs) (Xagorari and Chlichlia 2008). TLRs 3, 7, 8, and 9 are expressed in intracellular vesicles and recognize nucleic acids from viral origin (Cardoso et al. 2016a). Cattle experimentally infected with BHV5 showed an overexpression of TLRs 3, 7, and 9 in the frontal cerebral cortex, including the OBs, during acute infection and/or following virus reactivation (Marin et al. 2015). We have previously demonstrated that the host immune response and inflammation play a crucial role in the pathogenesis of acute encephalitis by BHV5 in cattle (Cardoso et al. 2016b). In many aspects, there Phensuximide is a consensus that BHV5 acute infection induces activation of pro-inflammatory cytokines and chemokines that eventually lead to brain injury, especially in frontal cortices (Marin et al. 2015). However, the portion/areas of the OBs more affected by inflammation process remain unclear. MicroRNAs (miRNAs) represent small RNA species composed by ~?20C14 nucleotides found in virtually all living organisms (Grey 2015; Sorel and Dewals 2016). Mature miRNAs are able to cause either mRNA degradation or translational repression regulating physiological process by target genes after their transcription (Glazov et al. 2009). Moreover, host miRNAs control herpesvirus infection by inhibiting viral or host transcripts (Piedade and Azevedo-Pereira 2016; Powdrill et al. 2016; Dickey et al. 2017). Recent data indicate that miR-155 plays a critical role in immunity, inflammation, and viral infections (Bhela et al. 2014; Dickey et al. 2016). Moreover, miR-155 is expressed in a variety of immune cells, including B cells, macrophages, types of T cells, NK cells, and dendritic cells Dickey et al. 2017). In addition, miR-155 modulation may act CLTB to control Japanese encephalitis virus infection (Pareek et al. 2004) and to enhance T cell trafficking in a model of coronavirus-induced neurological disease (Dickey et al. 2016). In fact, a number of studies have demonstrated that T cell responses are impaired in the absence of miR-155 during infection with some.