Immunosuppression of the Nasal Cavity by a Novel Pathogenic Pseudorabies Virus Isolation from Cattle in China

Abstract

The respiratory mucosa serves as a primary entry point for numerous pathogenic microbes, and the respiratory mucosa secretes type I and III interferons (IFNs), the first generation of antiviral cytokines, in response to viral infection. The pseudorabies virus (PRV) causes serious illnesses in many domestic and wild animal species, particularly in pigs and cattle. However, more information is needed about the immunosuppressive properties and evolutionary history of emerging PRV field strains in China’s respiratory system. The PRV field strain JS2022, which was obtained from a cow farm for this investigation, is a spontaneous recombination of early PRV variant strains in the Jiangsu region and is similar to the PRV variations recovered in China in terms of its entire genome sequence. According to sequence analysis, JS2022 has a spontaneous deletion of 1,212 bp in the gE gene, 502 bp in the gI gene, and 192 bp in the glycoprotein (g) C gene. Pathogenicity analysis revealed that intranasal JS2022 causes severe neurological symptoms in calves, but this effect is different from that of ZJ01. In addition, a considerable number of viral antigens in the nasal mucosa were detected by immunohistochemical staining. Therefore, we constructed a bovine nasal mucosal explant model that maintained good cell morphology and activity even after 5 days. In bovine nasal mucosal explants, JS2022 and ZJ01 can cause infection, and the viral load increases dramatically over time. Quantitative research revealed that 24 hr after infection, JS2022 dramatically reduced the expression of downstream interferon-stimulated genes and the innate immune factors IFN-β and IFN-λ3 and bovine nasal mucosal explants. Overall, our results highlight the significance of PRV surveillance in cattle and offer a resource for learning more about the clinical traits and development of PRV.