Pseudorabies Virus Infection Results in a Broad Inhibition of Host Gene Transcription

Romero, Nicolás; Wuerzberger-Davis, Shelly M.; Waesberghe, Cliff Van; Jansens, Robert J. J.; Tishchenko, A. B.; Verhamme, Ruth; Miyamoto, Shigeki; Favoreel, Herman

doi:10.1128/jvi.00714-22

Cited by 6 publications

(14 citation statements)

References 73 publications

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“…Quite to the contrary, PRV-infected MDBK cells at 8 hpi do show substantial and significantly increased nuclear import of NF-κB p65, in line with our earlier data ( Fig. 1D ) ( 9 , 12 , 13 ). In addition, the selected time points of analysis (8 hpi and 16 hpi) correspond to a very prominent virus-induced cytopathic effect, in both BoHV-1- and PRV-infected MDBK cells ( Fig.…”

Section: Resultssupporting

confidence: 92%

“…The interaction of alphaherpesviruses with NF-κB signaling in infected epithelial cells is mainly documented for HSV-1 and, to a lesser extent, PRV ( 9 , 12 , 13 ). HSV-1 infection triggers activation of the NF-κB cascade in epithelial cells, apparently in a biphasic manner and involving several viral proteins ( 10 , 11 , 14 – 19 ).…”

Section: Introductionmentioning

confidence: 99%

“…More recently, we found that PRV infection of immortalized as well as primary porcine epithelial cells leads to a gradual and unceasing degradation of the inhibitory IκBα protein and concomitant persistent nuclear translocation of NF-κB. However, despite this continuous activation of the pathway, NF-κB-dependent gene expression is blocked at the transcriptional level in the cell nucleus ( 9 , 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

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Several Alphaherpesviruses Interact Similarly with the NF-κB Pathway and Suppress NF-κB-Dependent Gene Expression

et al. 2023

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The current study provides a side-by-side comparison of the interaction of different alphaherpesviruses with NF-κB, a key and central player in the (proinflammatory) innate host response, in infected nontransformed epithelial cell lines. We report that all studied viruses prevent expression of the hallmark NF-κB-dependent gene IκB, often but not always via similar strategies, pointing to suppression of NF-κB-dependent host gene expression in infected epithelial cells as a common and therefore likely important aspect of alphaherpesviruses.

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Several Alphaherpesviruses Interact Similarly with the NF-κB Pathway and Suppress NF-κB-Dependent Gene Expression

et al. 2023

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“…In the process of virus infection, for the needs of self-proliferation, virions affect the NF-κB pathway through various mechanisms, thereby evading the host’s immune response [ 53 ]. The PRV-induced activation of the NF-κB pathway has some similarities with the activation of typical signaling pathways, but it also has its own characteristics [ 54 ]. The NF-κB signaling pathway mediated by TNF-α can be inhibited by the ICP0 protein of PRV [ 55 ], and the activation of this pathway can be substantially independent of the classical IκB kinase IKK while reducing the production of genes involved in negative feedback loops [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Dihydromyricetin Inhibits Pseudorabies Virus Multiplication In Vitro by Regulating NF-κB Signaling Pathway and Apoptosis

Zhao

Chen

Zhang

et al. 2023

Veterinary Sciences

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Pseudorabies virus (PRV) infections have caused huge economic losses to the breeding industry worldwide, especially pig husbandry. PRV could threaten human health as an easily ignored zoonotic pathogen. The emergence of new mutants significantly reduced the protective effect of vaccination, indicating an urgent need to develop specific therapeutic drugs for PRV infection. In this study, we found that dihydromyricetin (DMY) could dose-dependently restrain PRV infection in vitro with an IC50 of 161.34 μM; the inhibition rate of DMY at a concentration of 500 μM was 92.16 %. Moreover, the mode of action showed that DMY directly inactivated PRV virion and inhibited viral adsorption and cellular replication. DMY treatment could improve PRV-induced abnormal changes of the NF-κB signaling pathway and excessive inflammatory response through regulation of the contents of IκBα and p-P65/P65 and the transcriptional levels of cytokines (TNF-α, IL-1β and IL-6). Furthermore, DMY promoted the apoptosis of PRV-infected cells through the regulation of the expressions of Bax and Bcl-xl and the transcriptional levels of Caspase-3, Bax, Bcl-2 and Bcl-xl, thereby limiting the production of progeny virus. These findings indicated that DMY could be a candidate drug for the treatment of PRV infection.

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“…The primary clinical features of PR include high mortality encephalitis in newborn piglets, abortion and stillbirth in sows, as well as respiratory diseases and delayed growth in fattening pigs [ 1 ]. Since it was first discovered in Hungary in 1902, PRV has continued to cause significant economic losses around the world [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Screening and Stability Evaluation of Freeze-Dried Protective Agents for a Live Recombinant Pseudorabies Virus Vaccine

Liu,

Zhang,

Wang

et al. 2024

Vaccines

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Infection of pigs with the pseudorabies virus (PRV) causes significant economic losses in the pig industry. Immunization with live vaccines is a crucial aspect in the prevention of pseudorabies in swine. The TK/gE/gI/11k/28k deleted pseudorabies vaccine is a promising alternative for the eradication of epidemic pseudorabies mutant strains. This study optimized the lyophilization of a heat-resistant PRV vaccine to enhance the quality of a live vaccine against the recombinant PRV rHN1201TK−/gE−/gI−/11k−/28k−. The A4 freeze-dried protective formulation against PRV was developed by comparing the reduction in virus titer after lyophilization and after seven days of storage at 37 °C. The formulation contains 1% gelatin, 5% trehalose, 0.5% poly-vinylpyrimidine (PVP), 0.5% thiourea, and 1% sorbitol. The A4 freeze-dried vaccine demonstrated superior protection and thermal stability. It experienced a freeze-dried loss of 0.31 Lg post-freeze-drying and a heat loss of 0.42 Lg after being stored at a temperature of 37 °C for 7 consecutive days. The A4 freeze-dried vaccine was characterized through XRD, FTIR, and SEM analyses, which showed that it possessed an amorphous structure with a consistent porous interior. The trehalose component of the vaccine formed stable hydrogen bonds with the virus. Long-term and accelerated stability studies were also conducted. The A4 vaccine maintained viral titer losses of less than 1.0 Lg when exposed to 25 °C for 90 days, 37 °C for 28 days, and 45 °C for 7 days. The A4 vaccine had a titer loss of 0.3 Lg after storage at 2–8 °C for 24 months, and a predicted shelf life of 6.61 years at 2–8 °C using the Arrhenius equation. The A4 freeze-dried vaccine elicited no side effects when used to immunize piglets and produced specific antibodies. This study provides theoretical references and technical support to improve the thermal stability of recombinant PRV rHN1201TK−/gE−/gI−/11k−/28k− vaccines.

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Pseudorabies Virus Infection Results in a Broad Inhibition of Host Gene Transcription

Abstract: Herpesviruses are highly successful pathogens that cause lifelong persistent infections of their host. Modulation of the intracellular environment of infected cells is imperative for the success of virus infections.

Cited by 6 publications

References 73 publications

Several Alphaherpesviruses Interact Similarly with the NF-κB Pathway and Suppress NF-κB-Dependent Gene Expression

Several Alphaherpesviruses Interact Similarly with the NF-κB Pathway and Suppress NF-κB-Dependent Gene Expression

Dihydromyricetin Inhibits Pseudorabies Virus Multiplication In Vitro by Regulating NF-κB Signaling Pathway and Apoptosis

Screening and Stability Evaluation of Freeze-Dried Protective Agents for a Live Recombinant Pseudorabies Virus Vaccine

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