Insight into the Interaction Mechanism of Pseudorabies Virus Infection

Abstract

The pseudorabies virus (PRV), also known as suid alphaherpesvirus 1 (SuAHV-1), has garnered significant attention due to its broad host range and the economic losses it incurs in the swine industry. This review aims to provide a comprehensive understanding of the intricate virus-host interactions during PRV infection, focusing on the evasion strategies of the virus against the host responses. We also summarize the mechanisms by which PRV manipulates the host cell machinery to facilitate its replication and spread, while simultaneously evading detection and clearance by the immune system. Furthermore, we discuss the latest advancements, such as metabolic, autophagic, and apoptotic pathways in studying these interactions, highlighting the role of various cellular factors and pathways in elucidating virus-host dynamics. By integrating these insights, the article aims to provide a comprehensive overview of the molecular mechanisms underlying PRV pathogenesis and host response, paving the way for the development of novel therapeutic strategies against this virus.

Keywords: Aujeszky’s disease; pseudorabies virus; viral pathogenesis; virus–host interaction.

Figure 1

The structure of PRV virion and genome. (A) PRV virions consist of five components, encompassing a double-stranded DNA genome, an icosahedral protein capsid, a tegument protein layer, an envelope, and surface glycoproteins. (B) The PRV genome comprises the unique long region (UL) and unique short region (US), bordered by the internal repeat sequence (IRS) and terminal repeat sequence (TRS).

Figure 2

Factors involved in the regulation of cGAS–STING signaling during PRV infection. HSP27 and Brucella Omp 25 targets cGAS for degradation, while DDX56 and ZCCHC3 promote cGAS levels. Meanwhile, inhibition of HDAC1, PARP1, BRD4, or NMHC-IIA could enhance cGAS expression via inducing DNA damage or other pathways. ENPP1 positively regulates the homeostasis of cGAMP and PRDX1 interacts with TBK1.

Figure 3

The viral proteins directly target the cGAS–STING axis for proteasomal or lysosomal degradation. PRV infection triggers cGAS–STING signaling in the host, which in turn blocks PRV replication. While several viral proteins directly interact with the factors in this pathway, they target these immune factors for degradation, thus antagonizing the host innate immune response. UL21 recruits E3 ligase to degrade cGAS and STING via autophagy-lysosomal pathways. UL50 targets IFNAR1 for lysosomal degradation. UL24, UL13, and ICP0 target various immune factors for proteasomal degradation.