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

Abstract

Equine herpesvirus type 8 (EHV-8), associated with abortion and severe respiratory disease in donkeys and horses, causes significant economic losses in the global equine industry. However, the pathogenicity of EHV-8 is still unknown. Mice are widely used as an animal model to evaluate virus replication and virulence. The present study aimed to evaluate the pathogenicity of the EHV-8 SDLC66 strain in BALB/c mice. Mice were used to test for infection-associated parameters (such as clinical signs, body weights, virus replication in tissues, viremia, and cytokines) and sacrificed at 0, 2, 4, and 6 days post-infection (dpi). The mice inoculated with EHV-8 exhibited lethargy, dyspnea signs, loss in body weight, and viremia. EHV-8 was detected in the liver, spleen, brain, and lung by PCR at 4 dpi and 6 dpi, effectively replicating these tissues detected by TCID50 at 6 dpi. Proinflammatory cytokines, including IL-6, IL-1β, and TNF-α, were significantly increased at the 4 dpi and 6 dpi in the lung than in the control group. However, IFN-γ was only increased at 6 dpi in the EHV-8-infected group. These data showed that EHV-8 could enter the lungs of mice and cause respiratory disease in the mouse model, which helps reveal the pathogenicity of EHV-8.

Epidemiological investigation of equine herpesvirus in large-scale donkey farms in Liaocheng area and its effect on immunity and antioxidant capacity

“…Foote had higher positive groups than control groups in equine antibody detection for EHV-1 infection, and the same results as this test, EHV infection with donkeys increased the levels of IgA and IgG, indicating that EHV infection caused an immune response, and the host improved its resistance to the virus through a large amount of immune antibody secretion [28]. In 2022, Hu Leyufound by establishing an EHV-8 mouse infection model that the level of IL-6 in the lungs of mice after EHV-8 infection was the same as the increase in serum IL-6 in EHV donkey infection in this trial, indicating that EHV infection caused an in ammatory response and improved the expression of pro-in ammatory factors [29].…”

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

“…EHV-8 can cause respiratory disease and viral encephalitis in mouse models ( 1 , 27 ). Our data showed that hyperoside exerts a significant antiviral effect against EHV-8 in vitro .…”

“…The EHV-8 isolates used for this study were as follows: SDLC66 (GenBank: MW816102.1 ), SD2020113 (GenBank: MW822570.1 ), and donkey/Shandong/10/2021 (GenBank: OL856098.1 ). All strains were cultured in RK-13 cells, and their titers were measured using a plaque formation assay as described previously ( 27 ).…”

“…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.…”

Cobalt Protoporphyrin Blocks EqHV-8 Infection via IFN-α/β Production

“…The mice lungs of different groups at 8 dpi were collected for hematoxylin and eosin (HE) staining for evaluating histopathological changes as previously described [24]. Briefly, lungs were fixed in 10% formalin solution, underwent dehydration by alcohol, were transparentized in xylene, and then embedded in paraffin wax, sliced in a microtome (Leica, Nussloch, Germany) to 4 µm, affixed onto slides, followed by deparaffinization, clearance, diluted alcohols (95%, 75%), and hematoxylin solution stains, were differentiated, using 95% or 100% alcohol directly after the eosin stain, and, after cleared, placed on a coverslip to be observed by light microscopy.…”