Pathogenesis of Equid Alphaherpesvirus 1 Infection in the Central Nervous System of Mice

Abstract

Equid alphaherpesvirus 1 (EHV-1) causes myeloencephalopathy in horses and occasionally in non-equid species. Although mouse models have been developed to understand EHV-1 pathogenesis, few EHV-1 strains have been identified as highly neurovirulent to mice. The aim of this study was to evaluate the pathogenesis of 2 neurovirulent EHV-1 strains in mice, and to characterize the inflammatory cells and expression of chemokines and the apoptosis marker caspase-3 in the brain of infected mice. C57BL/6J mice were inoculated intranasally with EHV-1 strains A4/72 or A9/92 and evaluated on 1, 2, and 3 days post inoculation (DPI). EHV-1-infected mice showed severe neurological signs at 3 DPI. Ultrastructural analysis revealed numerous viral nucleocapsids and fewer enveloped virions within degenerated and necrotic neurons and in the surrounding neuropil. Histologically, at 3 DPI, there was severe diffuse neuronal degeneration and liquefactive necrosis, prominent microgliosis, and perivascular cuffing composed of CD3+ cells (T cells) and Iba-1+ cells (macrophages), mainly in the olfactory bulb and ventral portions of the brain. In these areas, moderate numbers of neuroglial cells expressed CCL5 and CCL2 chemokines. Numerous neurons, including those in less affected areas, were immunolabeled for cleaved caspase-3. In conclusion, neurovirulent EHV-1 strains induced a fulminant necrotizing lymphohistiocytic meningoencephalitis in mice, with microgliosis and expression of chemokines and caspase-3. This model will be useful for understanding the mechanisms underlying the extensive neuropathology induced by these viral infections.

Characterizing the Pathogenesis and Immune Response of Equine Herpesvirus 8 Infection in Lung of Mice

“…We also investigated the host’s viral behavior and immune response [ 21 , 22 ]. Several reports have indicated that mice can serve as animal models for EHVs infection [ 12 , 19 , 23 , 24 ]. However, the pathogenicity and immune response of EHV-8 in mice is still unknown.…”

“…To determine the EHV-8 replication in mice, a real-time PCR assay was used to detect EHV-8 in serum based on part ORF70 gene amplification with G1 F and R primers ( Table 1 ). The amplicons were inserted into the pMD18-T vector to generate recombinant plasmids, which were used to develop the real-time PCR assay as previously described [ 19 ]. Simultaneously, PCR was performed with G2 F and R primers ( Table 1 ) to detect the EHV-8 distribution in mice tissues at 2, 4, and 6 dpi.…”

Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways

“…This plasmid was used to develop a standard curve. Furthermore, the PCR assay for absolute quantification was performed as described previously ( 27 , 53 ). Briefly, DNA was extracted from the virus particles in the supernatant using the DNA Viral Genome Extraction Kit (Solarbio, China), and the DNA copies of EHV-8 were detected using qPCR and enumerated via normalization with the standard curve.…”

Equine Herpes Virus-1. A clinician’s perspective.

“…Since the early 70's most strains were distinguishable as respiratory (subtype 2) and abortigenic (subtype 1) (Burrows and Goodridge, 1973). On the contrary, pathogenic potential existence amongst EHV-1 family associated with neurological disease is still under investigation (Paillot et al, 2020;Mesquita et al, 2021).…”