Abstract
Meningoencephalitis by Herpesvirus type 5 (BoHV-5) in cattle has some features that are similar to those of herpetic encephalitis in humans and other animal species. Human Herpesvirus 3 (commonly known as Varicella-zoster virus 1), herpes simplex viruses (HSV), and equid Herpesvirus 1 (EHV-1) induce an intense inflammatory, vascular and cellular response. In spite of the many reports describing the histological lesions associated with natural and experimental infections, the immunopathological mechanisms for the development of neurological disorder have not been established. A total of twenty calf brains were selected from the Veterinary School, University of São Paulo State, Araçatuba, Brazil, after confirmation of BoHV-5 infection by virus isolation as well as by a molecular approach. The first part of the study characterized the microscopic lesions associated with the brain areas in the central nervous system (CNS) that tested positive in a viral US9 gene hybridization assay. The frontal cortex (Fc), parietal cortex (Pc), thalamus (T) and mesencephalon (M) were studied. Secondly, distinct pathogenesis mechanisms that take place in acute cases were investigated by an immunohistochemistry assay. This study found the frontal cortex to be the main region where intense oxidative stress phenomena (AOP-1) and synaptic protein expression (SNAP-25) were closely related to inflammatory cuffs, satellitosis and gliosis, which represent the most frequently observed neurological lesions. Moreover, MMP-9 expression was shown to be localized in the leptomeninges, in the parenchyma and around mononuclear infiltrates (p < 0.0001). These data open a new perspective in understanding the role of the AOP-1, MMP-9 and SNAP-25 proteins in mediating BoHV-5 pathogenesis and the strategies of host-virus interaction in order to invade de CNS.
Highlights
Bovine Herpesvirus type 5 (BoHV-5) is member of the family Herpesviridae, sub-family Alphaherpesvirinae, and is the primary etiological agent of non-suppurative meningoencephalitis, which is described as a cause of significant economic losses to beef cattle in Latin America [1]
Histopathology findings Brain lesions were mainly confined to the frontal cortex (Fc) and the parietal cortex (Pc) and were characterized as softening of parenchymal tissue and hemorrhagic foci in the Fc and Pc
An intense neuro-inflammation was described in all analyzed areas; it was almost exclusively seen in the Fc, Pc and thalamus (T) with a correlation coefficient of r = 0.8976
Summary
Bovine Herpesvirus type 5 (BoHV-5) is member of the family Herpesviridae, sub-family Alphaherpesvirinae, and is the primary etiological agent of non-suppurative meningoencephalitis, which is described as a cause of significant economic losses to beef cattle in Latin America [1]. The distribution of BoHV-5 DNA during the acute and latent phases of infection in experimentally infected rabbits and calves has been determined by amplification of glycoprotein C gene using the polymerase chain reaction (PCR) from brain suspensions [6]. To improve the in situ detection of viral genes, an in situ PCR protocol was established and used to implicate the olfactory bulb of the infected bovine CSN as the target region in natural cases of BoHV-5 infections [9]
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