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

SIMPLE SUMMARY: Equine herpesvirus 8 (EHV-8) is an important pathogen primarily affecting the horse and donkey industry, but there is little information about the pathogenicity and immune response of EHV-8 in a mouse model. We aim to investigate the pathogenicity and immune response in the lung during EHV-8 infection in BALB/c mice. The results showed that EHV-8 could effectively replicate and elicits a strong proinflammatory response in the lung tissues of a mouse model. The mouse model of viral respiratory disease proposed here will also be useful for studying the underlying mechanisms of the pathology of respiration. 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 TCID(50) 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.