Equine herpesvirus 1 elicits a strong pro-inflammatory response in the brain of mice

2021 ◽  
Author(s):  
Leonardo P. Mesquita ◽  
Rafael C. Costa ◽  
Dennis A. Zanatto ◽  
Fábio R. P. Bruhn ◽  
Laís L. R. Mesquita ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Cells ◽  
Interferon Γ ◽  
Innate Immune ◽  
Post Inoculation ◽  
Equine Herpesvirus ◽  
Herpesvirus Type ◽  
Equine Herpesvirus Type 1 ◽  
The Central Nervous System ◽  
The Brain

Equine herpesvirus type 1 (EHV-1) is an emerging pathogen that causes encephalomyelitis in horses and non-equid species. Several aspects of the immune response in the central nervous system (CNS), mainly regarding the role of inflammatory mediators during EHV-1 encephalitis, remain unknown. Moreover, understanding the mechanisms underlying extensive neuropathology induced by viruses would be helpful to establish therapeutic strategies. Therefore, we aimed to evaluate some aspects of the innate immune response during highly neurovirulent EHV-1 infection. C57BL/6 mice infected intranasally with A4/72 and A9/92 EHV-1 strains developed a fulminant neurological disease at 3 days post-inoculation with high viral titres in the brain. These mice developed severe encephalitis with infiltration of monocytes and CD8+ T cells to the brain. The inflammatory infiltrate followed the detection of the chemokines CCL2, CCL3, CCL4, CCL5, CXCL2, CXCL9 and CXCL-10 in the brain. Notably, the levels of CCL3, CCL4, CCL5 and CXCL9 were higher in A4/72-infected mice, which presented higher numbers of inflammatory cells within the CNS. Pro-inflammatory cytokines, such as interleukins (ILs) IL-1α, IL-1β, IL-6, IL-12β, and tumour necrosis factor (TNF), were also detected in the CNS, and Toll-like receptor (TLR) TLR2, TLR3 and TLR9 genes were also upregulated within the brain of EHV-1-infected mice. However, no expression of interferon-γ (IFN-γ) and IL-12α, which are important for controlling the replication of other herpesviruses, was detected in EHV-1-infected mice. The results show that the activated innate immune mechanisms could not prevent EHV-1 replication within the CNS, but most likely contributed to the extensive neuropathology. The mouse model of viral encephalitis proposed here will also be useful to study the mechanisms underlying extensive neuropathology.

Recombinant Glycoprotein B of Equine herpesvirus Type 1 Elicits Protective Immune Response against Challenge in BALB/c Mouse Model

2021 ◽  
Author(s):  
Alok Joshi ◽  
R.P. Gupta ◽  
Selvaraj Pavulraj ◽  
Bidhan Chandra Bera ◽  
Taruna Anand ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmid Dna ◽  
Protective Immune Response ◽  
Glycoprotein B ◽  
Equine Herpesvirus ◽  
Recombinant Glycoprotein ◽  
Herpesvirus Type ◽  
Equine Herpesvirus Type ◽  
Equine Herpesvirus Type 1

Background: Equine herpesvirus type 1 (EHV-1) is the most important viral pathogen of equines, causing respiratory illness, abortion, neonatal foal mortality and neurologic disorders. Large numbers of commercial EHV-1 vaccines are available to protect equines from the disease, but they provide only partial protection. Despite immunization with inactivated and modified live virus vaccine, mares show abortions. Present study was aimed to investigate the immunogenicity and protective efficacy of EHV-1 recombinant glycoprotein B (rgB) and gB expressing plasmid DNA against EHV-1 infection in BALB/c mice model.Methods: About 3-4 weeks old 225 female BALB/c mice were selected for the comparative study of immunization followed by challenged with EHV-1/India/Tohana/96-2 strain virus in 5 different groups of 45 animals each.Result: Following immunization, rgB vaccinated mice showed optimal stimulation of EHV-1 gB specific cell mediated and humoral mediated immunity (HMI and CMI). The gB expressing plasmid DNA vaccinated mice developed only CMI while inactivated whole virus vaccinated mice had only HMI. Upon EHV-1 challenge, all infected mice displayed variable levels of clinical signs with changes in body weight, however, vaccinated mice showed very rapid recovery with optimal protection. Positive control group mice showed severe pulmonary lesions along with persistence virus infection till 5 days post challenge (dpc) whereas vaccinated mice had less pulmonary lesion only up to 3dpc. Minimal lung lesions and early virus clearance was observed in the rgB immunized mice in comparison to the gB plasmid DNA and inactivated EHV-1 vaccine immunized mice. It has been concluded that immunization with rgB elicits optimum protective immune response against EHV-1 infection in mice model. The rgB could be a potential vaccine candidate against EHV-1 infection in equine in the future.

scholarly journals Novel Technologies in Studying Brain Immune Response

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Li Li ◽  
Cameron Lenahan ◽  
Zhihui Liao ◽  
Jingdong Ke ◽  
Xiuliang Li ◽  
...  
Keyword(s):  
Immune Response ◽  
Neurological Diseases ◽  
Structural Complexity ◽  
Innate Immune ◽  
Brain Repair ◽  
Novel Technologies ◽  
Novel Treatments ◽  
The Central Nervous System ◽  
Immunomodulatory Therapies ◽  
The Brain

Over the past few decades, the immune system, including both the adaptive and innate immune systems, proved to be essential and critical to brain damage and recovery in the pathogenesis of several diseases, opening a new avenue for developing new immunomodulatory therapies and novel treatments for many neurological diseases. However, due to the specificity and structural complexity of the central nervous system (CNS), and the limit of the related technologies, the biology of the immune response in the brain is still poorly understood. Here, we discuss the application of novel technologies in studying the brain immune response, including single-cell RNA analysis, cytometry by time-of-flight, and whole-genome transcriptomic and proteomic analysis. We believe that advancements in technology related to immune research will provide an optimistic future for brain repair.

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

2021 ◽  
pp. 030098582110206
Author(s):  
Leonardo P. Mesquita ◽  
Rafael C. Costa ◽  
Laís L. R. Mesquita ◽  
Maria do Carmo C. S. H. Lara ◽  
Eliana M. C. Villalobos ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Viral Infections ◽  
Neuronal Degeneration ◽  
Inflammatory Cells ◽  
Post Inoculation ◽  
Neurological Signs ◽  
Liquefactive Necrosis ◽  
The Central Nervous System ◽  
The Brain ◽  
Apoptosis Marker

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.

scholarly journals Replication kinetics of neurovirulent versus non-neurovirulent equine herpesvirus type 1 strains in equine nasal mucosal explants

2010 ◽  
Vol 91 (8) ◽  
pp. 2019-2028 ◽  
Author(s):  
Annelies P. Vandekerckhove ◽  
S. Glorieux ◽  
A. C. Gryspeerdt ◽  
L. Steukers ◽  
L. Duchateau ◽  
...  
Keyword(s):  
Post Inoculation ◽  
Equine Herpesvirus ◽  
Upper Respiratory Tract ◽  
Herpesvirus Type ◽  
Equine Herpesvirus Type ◽  
Equine Herpesvirus Type 1 ◽  
Infected Cells ◽  
Mucosal Explants

Equine herpesvirus type 1 (EHV-1) is the causative agent of equine herpes myeloencephalopathy, of which outbreaks are reported with increasing frequency throughout North America and Europe. This has resulted in its classification as a potentially emerging disease by the US Department of Agriculture. Recently, it was found that a single nucleotide polymorphism (SNP) in the viral DNA polymerase gene (ORF30) at aa 752 (N→D) is associated with the neurovirulent potential of EHV-1. In the present study, equine respiratory mucosal explants were inoculated with several Belgian isolates typed in their ORF30 as D752 or N752, to evaluate a possible difference in replication in the upper respiratory tract. In addition, to evaluate whether any observed differences could be attributed to the SNP associated with neurovirulence, the experiments were repeated with parental Ab4 (reference neurovirulent strain), parental NY03 (reference non-neurovirulent strain) and their N/D revertant recombinant viruses. The salient findings were that EHV-1 spreads plaquewise in the epithelium, but plaques never cross the basement membrane (BM). However, single EHV-1-infected cells could be observed below the BM at 36 h post-inoculation (p.i.) for all N752 isolates and at 24 h p.i. for all D752 isolates, and were identified as monocytic cells and T lymphocytes. Interestingly, the number of infected cells was two to five times higher for D752 isolates compared with N752 isolates at every time point analysed. Finally, this study showed that equine respiratory explants are a valuable and reproducible model to study EHV-1 neurovirulence in vitro, thereby reducing the need for horses as experimental animals.

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