A Tug of War: Pseudorabies Virus and Host Antiviral Innate Immunity

Abstract

The non-specific innate immunity can initiate host antiviral innate immune responses within minutes to hours after the invasion of pathogenic microorganisms. Therefore, the natural immune response is the first line of defense for the host to resist the invaders, including viruses, bacteria, fungi. Host pattern recognition receptors (PRRs) in the infected cells or bystander cells recognize pathogen-associated molecular patterns (PAMPs) of invading pathogens and initiate a series of signal cascades, resulting in the expression of type I interferons (IFN-I) and inflammatory cytokines to antagonize the infection of microorganisms. In contrast, the invading pathogens take a variety of mechanisms to inhibit the induction of IFN-I production from avoiding being cleared. Pseudorabies virus (PRV) belongs to the family Herpesviridae, subfamily Alphaherpesvirinae, genus Varicellovirus. PRV is the causative agent of Aujeszky's disease (AD, pseudorabies). Although the natural host of PRV is swine, it can infect a wide variety of mammals, such as cattle, sheep, cats, and dogs. The disease is usually fatal to these hosts. PRV mainly infects the peripheral nervous system (PNS) in swine. For other species, PRV mainly invades the PNS first and then progresses to the central nervous system (CNS), which leads to acute death of the host with serious clinical and neurological symptoms. In recent years, new PRV variant strains have appeared in some areas, and sporadic cases of PRV infection in humans have also been reported, suggesting that PRV is still an important emerging and re-emerging infectious disease. This review summarizes the strategies of PRV evading host innate immunity and new targets for inhibition of PRV replication, which will provide more information for the development of effective inactivated vaccines and drugs for PRV.

Pseudorabies virus exploits N6-methyladenosine modification to promote viral replication

“…m 6 A modification was involved in regulating the host immune response to various viral infections (Mcfadden and Horner, 2021), and many viruses utilized m 6 A modification to evade host innate immunity (Kim et al, 2020;Lu et al, 2020Lu et al, , 2021Xue et al, 2021). PRV had evolved a variety of host immune escape mechanisms (Ye et al, 2022), so m 6 A modification might be involved in regulating host immune escape after PRV infection. KEGG analysis showed that the water reabsorption pathway was the first pathway involved by hypomethylated genes, which might be due to the selection of kidney cell lines.…”

Progress on innate immune evasion and live attenuated vaccine of pseudorabies virus

“…The IFN-I-mediated innate immune response is one of the most effective defense strategies of the host against viral infection. However, viruses have developed various strategies to evade host immunity during their long evolution (Garcia-Sastre, 2017;O'Connor and Sen, 2021;Verzosa et al, 2021;Ye et al, 2022). PRV regulates the host innate immune responses in several strategies.…”

Host Combats IBDV Infection at Both Protein and RNA Levels

“…Subsequently, the adaptive immune response is elicited to facilitate the clearance of pathogens and the generation of immunological memory [ 28 ]. Meanwhile, pathogens have also developed multiple mechanisms to escape the host immune response [ 29 ]. Thus, the war between virus and host always continues.…”