Host antiviral protein IFITM2 restricts pseudorabies virus replication

Xie, Jingyuan; Bi, Yingjie; Xu, Shujuan; Han, Yanping; Idris, Adi; Zhang, Haixia; Li, Xiangrong; Bai, Jialin; Zhang, Yong; Feng, Ru

doi:10.1016/j.virusres.2020.198105

Cited by 25 publications

(22 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cellular RNA was isolated and reverse-transcribed to cDNA. Methods were performed as previously described [ 22 ]. Primers for RT-qPCR are available upon request.…”

Section: Methodsmentioning

confidence: 99%

Pseudorabies Virus ICP0 Abolishes Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Degrading P65

Zhang

Xie

Ming

et al. 2022

Viruses

Self Cite

View full text Add to dashboard Cite

Nuclear factor κB (NF-κB) is involved in a wide range of innate immune activities in host cells and serves as an important component of a host’s immunity system. To survive in infected cells, viruses have evolved intricate strategies to evade the host immune response. Pseudorabies virus (PRV) is a member of the alpha herpesvirus family and is capable of causing reproductive and neurological dysfunction in pigs. PRV has a large DNA genome and therefore has the ability to encode numerous proteins that modulate host innate immune responses. In the present study, we demonstrated that the PRV-encoded immediate early protein ICP0 inhibits the tumor necrosis factor alpha (TNF-α)-mediated NF-κB signaling pathway. An in-depth study showed that ICP0 protein was able to limit NF-κB activation and decreased the expression of inflammatory cytokines interleukin-6 (IL-6) and interleukin 8 (IL-8). In addition, ICP0 blocked the activation of NF-κB through interacting with p65, degrading its protein expression and limiting its phosphorylation. PRV protein ICP0 is shown for the first time to enable escape from innate immune response through the regulation of NF-κB during PRV infection. These results illustrate that PRV ICP0 is able to block NF-κB activation. This mechanism may represent a critical role in the early events leading to PRV infection.

show abstract

“…Cellular RNA was isolated and reverse-transcribed to cDNA. Methods were performed as previously described [ 22 ]. Primers for RT-qPCR are available upon request.…”

Section: Methodsmentioning

confidence: 99%

Pseudorabies Virus ICP0 Abolishes Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Degrading P65

Zhang

Xie

Ming

et al. 2022

Viruses

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, IFN-inducible transmembrane proteins (IFITM1, 2, 3) are found to work as important host self-restriction factors, possessing a broad spectrum of antiviral effects. Xie et al IFITM2 are crucial for controlling PRV infection by interfering with cell binding and entry [ 94 ]. However, Wang et al found that knockdown of IFITM2 and IFITM3 expression don’t influence PRV infection.…”

Section: Prv Infection Inhibits Ifn Signaling Pathwaymentioning

confidence: 99%

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

Zhou

et al. 2022

Viruses

View full text Add to dashboard Cite

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.

show abstract

“…Cellular RNA was isolated and reverse-transcribed to cDNA. Methods were performed as previously described (Xie et al, 2020). Primers for RT-qPCR are available upon request.…”

Section: Co-immunoprecipitation Assaymentioning

confidence: 99%

Pseudorabies Virus US3 Protein Inhibits IFN-β Production by Interacting With IRF3 to Block Its Activation

et al. 2021

Self Cite

View full text Add to dashboard Cite

Pseudorabies virus is a typical swine alphaherpesvirus, which can cause obvious neurological disorders and reproductive failure in pigs. It is capable of evading host antiviral immune response. However, the mechanism by which many PRV proteins assist the virus to evade innate immunity is not fully understood. This study identified PRV US3 protein as a crucial antagonistic viral factor that represses interferon beta (IFN-β) expression. A in-depth study showed that US3 protein restricted type I IFN production by targeting interferon regulatory factor 3 (IRF3), a key molecule required for type I IFN induction. Additionally, US3 protein interacted with IRF3, degraded its protein expression to block the phosphorylation of IRF3. These findings suggested a novel strategy utilized by PRV to inhibit IFN-β production and escape the host innate immunity.

show abstract

Host antiviral protein IFITM2 restricts pseudorabies virus replication

Abstract: Highlights Type I IFN and IFITMs showed marked upregulation following PRV infection in PK15 cells. IFITM proteins restricted PRV infection by interfering virus binding and entry. IFITM2-mediated inhibition of PRV entry requires the cholesterol pathway.

Cited by 25 publications

References 54 publications

Pseudorabies Virus ICP0 Abolishes Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Degrading P65

Pseudorabies Virus ICP0 Abolishes Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Degrading P65

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

Pseudorabies Virus US3 Protein Inhibits IFN-β Production by Interacting With IRF3 to Block Its Activation

Contact Info

Product

Resources

About