Molecular epidemiology and immunopathogenesis of bovine viral diarrhea virus: a growing threat to regional cattle industry of Xinjiang, China

Abstract

Bovine viral diarrheal virus (BVDV), identified as a serious global pathogen, presents a significant and formidable challenge for the global cattle sector. This presents not only serious economic consequences but also serious immunopathological consequences causing lasting impacts. In the Chinese province of Xinjiang, where the ruminants are high and the topographical features unique and contribute towards complex epidemiology, multiple genotypes of the BVDV are continuously interacting and adapting. This includes the persistent presence of the earlier predominant BVDV1, the rising trend towards the antigenically complex BVDV2, and the recent presence of the HoBi-like (BVDV3) strain, contributing toward complexity. The purpose of this review is to present a detailed analysis relative to the molecular epidemiology, genomic diversity levels, and complex pathology associated with the persistence and spreading of the infection by the BVDV. In light of the country's inability to execute the efficacious eradication of the infection, stringent biosafety measures need to be adopted, the genomic investigation has to be increased, and the establishment of the multi-valent vaccine for the induction of the local strain of the infection should be encouraged. These steps need to be taken towards the rising danger of the presence of the BVDV, not only towards the province but also towards the larger territories beyond.

Keywords: Xinjiang; bovine viral diarrhea; bovine viral diarrhea virus; epidemiology; pathogenesis; prevalence.

Figure 1

BVDV’s structural morphology and genomic translation into structural and nonstructural proteins for viral assembly. The outermost layer is the lipid envelope, studded with envelope (E) glycoproteins, including the secreted Erns proteins visible as black dots. Beneath the envelope lie the E1 and E2 heterodimers, crucial for viral entry. The yellow layer represents the nucleocapsid protein C, which encapsulates the viral RNA genome (shown in green). Created in BioRender. F. Kulyar, M. (2025) https://BioRender.com/p95yur0.Kulya.

Figure 2

The phylogenetic analysis of bovine viral diarrhea virus.

Figure 3

The replication cycle of bovine viral diarrhea virus (BVDV). This detailed schematic illustrates the key steps in BVDV infection and replication. The process also highlights the formation of the replication complex and the production of structural proteins, emphasizing the intricate cellular mechanisms exploited by BVDV for its propagation. It further provides insights into potential targets for antiviral strategies and vaccine development against BVDV. Created in BioRender. F. Kulyar, M. (2025) https://BioRender.com/6penelu.

Figure 4

BVDV-mediated inhibition of RLR signaling pathway. The virus is recognized by the RLR sensor MDA5 (melanoma differentiation-associated protein 5), leading to its activation. This activation triggers the downstream signaling cascade, where MDA5 interacts with the mitochondrial antiviral-signaling protein (MAVS), leading to the recruitment of TBK1 and IKKε kinases. These kinases phosphorylate IRF3 (interferon regulatory factor 3), promoting its translocation to the nucleus and the subsequent production of type I interferons (IFN-α/β). Created in BioRender. F. Kulyar, M. (2025) https://BioRender.com/glqkilx.

Figure 5

The blockage of host’s IFN activated immune response by Npro and IRF3 degradation. Cellular PRRs recognize PAMPs of viral infection. Such recognition thus triggers a sequence of cellular pathways that eventually lead to the translocation of phosphorylated IRF3 into the nucleus and commence the transcription of type I interferon genes through binding to IFN-α/β promoters. Npro might bind with IRF3 prior to its activation induced by phosphorylation, thereby targeting IRF-3 for ubiquitination and subsequent proteasomal degradation, resulting in a block in the type I interferon response. Created in BioRender. F. Kulyar, M. (2025) https://BioRender.com/j4sbip1.

Figure 6

The dissemination of BVDV from persistently infected animals to other healthy animals and calves. Created in BioRender. F. Kulyar, M. (2025) https://BioRender.com/m5lufia.