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Brain tissue of an unvaccinated control pig (A) and pig inoculated with pseudorabies virus strain HeN1 (B). Arrows indicate lymphocyte infiltration around the small blood vessels in the brain cortex. Original magnification ×100.
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The widely used pseudorabies virus (PRV) Bartha-K61 vaccine has played a key role in the eradication of PRV. Since late 2011, however, a disease characterized by neurologic symptoms and a high number of deaths among newborn piglets has occurred among Bartha-K61-vaccinated pigs on many farms in China. Clinical samples from pigs on 15 farms in 6 prov...
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Background:
Pseudorabies virus (PRV) protein UL56 (pUL56) has been implicated in viral dissemination and virulence in vivo. However, the properties of PRV pUL56 remain largely unknown. In the present study, we aim to investigate the subcellular localization of pUL56 and the underlying molecular basis in transfected cells.
Methods:
Constructs of...
Citations
... Since the 1970s, when China imported the Bartha-K61 vaccine from Hungary, the incidence rate and newborn piglet mortality in infected pig herds have dramatically decreased to less than 10% [4,6]. However, since 2011, outbreaks of variant PRV have been reported at many large-scale aquaculture farms in China [7,8,9,10]. The fact that more cases of PRV infection in humans have been documented in China since 2018 is especially notable since it suggests that there is a new animalderived viral hazard to human health, especially in light of the appearance of new mutant strains. ...
The respiratory mucosa serves as a primary entry point for numerous pathogenic microbes, and the respiratory mucosa secretes type I and III interferons (IFNs), the first generation of antiviral cytokines, in response to viral infection. The pseudorabies virus (PRV) causes serious illnesses in many domestic and wild animal species, particularly in pigs and cattle. However, more information is needed about the immunosuppressive properties and evolutionary history of emerging PRV field strains in China’s respiratory system. The PRV field strain JS2022, which was obtained from a cow farm for this investigation, is a spontaneous recombination of early PRV variant strains in the Jiangsu region and is similar to the PRV variations recovered in China in terms of its entire genome sequence. According to sequence analysis, JS2022 has a spontaneous deletion of 1,212 bp in the gE gene, 502 bp in the gI gene, and 192 bp in the glycoprotein (g) C gene. Pathogenicity analysis revealed that intranasal JS2022 causes severe neurological symptoms in calves, but this effect is different from that of ZJ01. In addition, a considerable number of viral antigens in the nasal mucosa were detected by immunohistochemical staining. Therefore, we constructed a bovine nasal mucosal explant model that maintained good cell morphology and activity even after 5 days. In bovine nasal mucosal explants, JS2022 and ZJ01 can cause infection, and the viral load increases dramatically over time. Quantitative research revealed that 24 hr after infection, JS2022 dramatically reduced the expression of downstream interferon-stimulated genes and the innate immune factors IFN-β and IFN-λ3 and bovine nasal mucosal explants. Overall, our results highlight the significance of PRV surveillance in cattle and offer a resource for learning more about the clinical traits and development of PRV.
... This disease is a severe feverish infection that is known for causing disorders in the nervous system and high death rates among piglets. It also leads to respiratory problems and weight loss of finishing pigs, as well as reduced fertility in female pigs [1]. This disease has resulted in significant financial losses for the global breeding industry. ...
Natural immunity is the first defense line of the host immune system, which plays a significant role in combating foreign pathogenic microorganisms. The IFN-β (interferon-beta) signaling pathway, being a typical example of innate immunity, plays a vital function. This study aimed to elucidate the function of pseudorabies virus (PRV) UL38 protein (unique long region 38) in suppressing the activation of the IFN-β signaling pathway. The findings from our study indicate that the PRV UL38 protein effectively hampers the activation of IFN-β by poly (dA: dT) (poly(deoxyadenylic-deoxythymidylic)) and 2’3’-cGAMP (2’-3’-cyclic GMP-AMP). Furthermore, UL38 exhibits spatial co-localization with STING (stimulator of interferon genes) and effectively hinders STING dimerization. Subsequently, STING was downgraded to suppress the production of IFN-β and ISGs (interferon stimulated genes). Immunoprecipitation analysis revealed that the interaction between UL38 and STING, which subsequently initiated the degradation of STING via selective autophagy mediated by TOLLIP (toll interacting protein). To summarize, this research elucidates the function of UL38 in counteracting the cGAS (cGAMP synthase)-STING-induced IFN-β pathway. The PRV UL38 protein may attenuate the activation of IFN-β as a means of regulating the virus’s persistence in the host.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12985-024-02379-x.
... Researchers found that the PRV mutant strain JS-2012 resulted in earlier and more severe clinical symptoms, as well as higher mortality, when compared with the PRV classic strain SC [38]. Based on protection tests, the Bartha-K61 vaccine provided 100% protection against the classic strain but only partially against JS-2012 and HeN1 strains [38][39][40]. However, in other studies, it was confirmed that the Bartha-K61 vaccine can protect nursery pigs and growing pigs against emerging variants of PRV, such as the HeN1 and XJ5 strains [24,[41][42][43]. ...
In recent years, pseudorabies virus (PRV) variants have resulted in an epidemic in swine herds and huge economic losses in China. Therefore, it is essential to develop an efficacious vaccine against the spread of PRV variants. Here, the triple-gene-deletion virus and the triple-gene-deletion plus gC virus were constructed by homologous recombination (HR). And then, their growth capacity, proliferation ability, and immune efficacy were evaluated. The results showed that the growth kinetics of the recombinant viruses were similar to those of the parental strain PRV-AH. Compared with the triple-gene-deletion virus group, the more dominant level of neutralizing antibody (NA) can be induced in the triple-gene-deletion plus gC virus group with the same 106.0 TCID50 dose after 4 and 6 weeks post-initial immunization (PII) (p < 0.0001). In addition, the antibody titers in mice immunized with the triple-gene-deletion plus gC virus were significantly higher than those immunized with triple-gene deletion virus with the same 105.0 TCID50 dose after 6 weeks PII (p < 0.001). More importantly, in the triple-gene-deletion plus gC virus group with 105.0 TCID50, the level of NA was close to that in the triple-gene deletion virus group with 106.0 TCID50 at 6 weeks PII. Meanwhile, the cytokines IL-4 and IFN-γ in sera were tested by enzyme-linked immunosorbent assay (ELISA) in each group. The highest level of IL-4 or IFN-γ was also elicited in the triple-gene deletion plus gC virus group at a dose of 106.0 TCID50. After challenge with PRV-AH, the survival rates of the triple-gene deletion plus gC virus immunized groups were higher than those of other groups. In immunized groups with 105.0 TCID50, the survival rate shows a significant difference between the triple-gene deletion plus gC virus group (75%, 6/8) and the triple-gene deletion virus group (12.5%, 1/8). In general, the immune efficacy of the PRV TK/gI/gE-deleted virus can be increased with additional gC insertion in mice, which has potential for developing an attenuated vaccine candidate for PRV control.
... Although gene-deleted PRV live vaccination such as Bartha-K61 vaccines is well implemented in most countries and the prevalence of the virus is effectively controlled, it remains an essential pathogen in the pig industry (8,9). However, since 2011, many PRV variants have occurred along with increased virulence, and the classical Bartha-K61 vaccine could not provide complete protection against PRV variants (10,11). Moreover, increasing numbers of studies have reported human cases of PRV infection accompanied by classic clinical symptoms of fever and inflammation, suggesting that PRV poses a significant threat to mammals and even to humans and is a growing threat to public and human health (12). ...
Pseudorabies virus (PRV) is the causative agent of Aujeszky’s disease, which is responsible for enormous economic losses to the global pig industry. Although vaccination has been used to prevent PRV infection, the effectiveness of vaccines has been greatly diminished with the emergence of PRV variants. Therefore, there is an urgent need to develop anti-PRV drugs. Polyethylenimine (PEI) is a cationic polymer and has a wide range of antibacterial and antiviral activities. This study found that a low dose of 1 µg/mL of the 25-kDa linear PEI had significantly specific anti-PRV activity, which became more intense with increasing concentrations. Mechanistic studies revealed that the viral adsorption stage was the major target of PEI without affecting viral entry, replication stages, and direct inactivation effects. Subsequently, we found that cationic polymers PEI and Polybrene interfered with the interaction between viral proteins and cell surface receptors through electrostatic interaction to exert the antiviral function. In conclusion, cationic polymers such as PEI can be a category of options for defense against PRV. Understanding the anti-PRV mechanism also deepens host-virus interactions and reveals new drug targets for anti-PRV.
IMPORTANCE
Polyethylenimine (PEI) is a cationic polymer that plays an essential role in the host immune response against microbial infections. However, the specific mechanisms of PEI in interfering with pseudorabies virus (PRV) infection remain unclear. Here, we found that 25-kDa linear PEI exerted mechanisms of antiviral activity and the target of its antiviral activity was mainly in the viral adsorption stage. Correspondingly, the study demonstrated that PEI interfered with the virus adsorption stage by electrostatic adsorption. In addition, we found that cationic polymers are a promising novel agent for controlling PRV, and its antiviral mechanism may provide a strategy for the development of antiviral drugs.
... Genotype II strains are mainly concentrated in China and are further divided into classical and variant strains. The Fa [31], Ea [32], and SC [33] strains belong to the group of classical strains, and the HeN1 [34], TJ [35], and JS-2012 [36] strains are variant strains. The vaccine strain Bartha-K61 belongs to genotype I [37], and vaccine preparations based on this strain do not provide comprehensive protection against the PRV variants found in Asian countries [38,39]. ...
African swine fever (ASF) is an infectious disease caused by ASF virus (ASFV), which is characterized by high infectivity, rapid onset of disease, and a high mortality rate. Outbreaks of ASFV have caused great economic losses to the global pig industry, and there is a need to develop safe and effective vaccines. In this study, two recombinant pseudorabies virus (PRV) strains, rGXGG-2016-ΔgI/ΔgE-EP364R and rGXGG-2016-ΔgI/ΔgE-B119L, expressing the EP364R and B119L protein, respectively, of ASFV, were constructed by homologous recombination technology. Western blotting and immunofluorescence analysis showed that these foreign proteins were expressed in cells infected with the recombinant strains. The strains showed good genetic stability and proliferative characteristics for 20 passages in BHK-21 cells. Both of these strains were immunogenic in mice, inducing the production of specific antibodies against the expressed ASFV proteins while providing protection against lethal challenge with PRV. Thus, the recombinant strains rGXGG-2016-ΔgI/ΔgE-EP364R and rGXGG-2016-ΔgI/ΔgE-B119L could be used as candidate vaccines for both ASFV and PRV. In addition, our study identifies two potential target genes for the development of safe and efficient ASFV vaccines, provides a reference for the construction of bivalent ASFV and PRV vaccines, and demonstrates the feasibility of developing a live ASFV vector vaccine.
... A total amount of 1 µg RNA per sample was used as input material for the RNA sample preparations. Sequencing libraries were generated using NEBNext® UltraTM RNA Library Prep Kit for Illumina® (NEB, USA) following manufacturer's recommendations, and index codes were added to attribute sequences to each sample [19]. This kit was used to prepare sequencing libraries from total RNA. ...
... Pseudorabies virus (PRV) is a pathogen that causes up to 50% mortality in newborn piglets, severely impacting the pig industry. The Bartha-K61 vaccine protects against lethal infection by classical PRV strains but not emerging variants [19]. Gene knockouts of gE/gl/TK successfully attenuate PRV, and the TK gene is an important virulence factor in PRV variants. ...
Background
Pseudorabies virus (PRV) causes substantial losses in the swine industry worldwide. Attenuated PRV strains with deletions of immunomodulatory genes glycoprotein E (gE), glycoprotein I (gI) and thymidine kinase (TK) are candidate vaccines. However, the effects of gE/gI/TK deletions on PRV-host interactions are not well understood.
Methods
To characterize the impact of gE/gI/TK deletions on host cells, we analyzed and compared the transcriptomes of PK15 cells infected with wild-type PRV (SD2017), PRV with gE/gI/TK deletions (SD2017gE/gI/TK) using RNA-sequencing.
Results
The attenuated SD2017gE/gI/TK strain showed increased expression of inflammatory cytokines and pathways related to immunity compared to wild-type PRV. Cell cycle regulation and metabolic pathways were also perturbed.
Conclusions
Deletion of immunomodulatory genes altered PRV interactions with host cells and immune responses. This study provides insights into PRV vaccine design.
... Despite successful control or eradication of pseudorabies (PR) in many countries through vaccination, the epidemic remains prevalent in Chinese pigs (16). Despite immunization with the PR Bartha-K61 deficiency vaccine, numerous outbreaks of PRV have occurred (13,(17)(18)(19)(20)(21). In 2018, there was an outbreak of African swine fever in China, which had a significant impact on the country's swine farming industry. ...
Introduction
Pseudorabies virus (PRV) is a linear DNA virus with a double-stranded structure, capable of infecting a diverse array of animal species, including humans. This study sought to ascertain the seroprevalence of Pseudorabies Virus (PRV) in China by conducting a comprehensive collection of blood samples from 16 provinces over the course of 2022.
Methods
The presence of PRV gE antibodies was detected through the utilization of an enzyme-linked immunosorbent assay (ELISA) technique. Logistic regression analysis was conducted to identify potential related factors associated with the serologic status of PRV gE at the animal level. Additionally, the SaTScan 10.1 software was used to analyze the spatial and temporal clusters of PRV gE seroprevalence.
Results
A comprehensive collection of 161,880 samples was conducted, encompassing 556 swine farms throughout the country. The analysis revealed that the seroprevalence of PRV gE antibodies was 12.36% (95% confidence interval [CI], 12.20% to 12.52%) at the individual animal level. However, at the swine farm level, the seroprevalence was considerably higher, reaching 46.22% (95% CI, 42.08% to 50.37%). Related factors for PRV infection at the farm level included the geographic distribution of farms and seasonal variables. Moreover, five distinct high seroprevalence clusters of PRV gE were identified across China, with the peak prevalence observed during the months of April through June 2022.
Conclusion
Our findings serve as a valuable addition to existing research on the seroprevalence, related factors, and temporal clustering of PRV gE in China. Furthermore, our study provides a reference point for the development of effective strategies for the prevention and control of pseudorabies and wild virus outbreaks.
... PRV has been very harmful for swine herds, especially since 2011. Some pig farms in China that had immunized their herds with traditional commercial PRV vaccines have experienced a new round of PRV infection, caused by PRV mutants, and these mutant viruses are severely affecting the pig industry in China [2][3][4]. At present, the prevention and control of PRV in pig farms relies mainly on vaccination. ...
Pseudorabies virus (PRV) has spread widely in swine herds since it was introduced into China, and PRV variants have appeared in many regions in China since 2011. Owing to the ongoing emergence of viral mutations, the protective efficacy of PRV vaccines faces great challenges. Gossypol is a polyphenolic natural compound purified from cotton roots, stems, or seeds. This study found that gossypol has a notable inhibitory effect on PRV. Based on the biological effects of gossypol, the anti-PRV effect of gossypol was studied from the aspects of mitochondrial damage, reactive oxygen species, energy metabolism, and autophagy. The results showed that gossypol had no direct inactivation effect on PRV in solution within concentrations of ≤3 µM; gossypol did not stimulate interferon-β to exert an anti-PRV effect by triggering mitochondrial DNA leakage; the anti-PRV effect of gossypol was reactive oxygen species and ATP-independent in cells; and the PRV-inhibitory effect of gossypol was independent of its induced autophagy. By adding gossypol to PRV-infected cells at different stages of infection and performing virus titer detection, atomic force microscopy, qPCR, fluorescence microscopy, and firefly luciferase activity assays, we found that gossypol exerted an anti-PRV effect by inhibiting the adsorption of PRV on the cell surface.
... Cross-species transmission of viruses occurs frequently, and the protection capability of vaccines has become increasingly insufficient. In China, since 2011, multiple mutant strains of PRV have been isolated from pig farms that were previously vaccinated with the pseudorabies vaccine (Leng et al. 2013). These mutant strains are more pathogenic than the nonmutant PRV strains ). ...
The rapid expansion of large-scale pig farming has brought about a surge in viral diseases with high morbidity rates and diverse manifestations. This widespread occurrence of multiple viral diseases in pig farms has inflicted severe economic losses on the global swine industry. Consequently, there is an urgent need for eco-friendly and efficient antiviral drugs that can effectively combat viruses and prevent diseases such as PEDV, PRRSV, PRV, and other viral infections. To this end, we conducted a study on the antiviral activity and cytotoxicity of eleven different Chinese herbal extracts (CHE) against PRV. In vitro testing of several extracts, namely, Echinacea, Ilex purpurea Hassk, Ganoderma lucidum Kars, Taraxacum mongolicum, and Ilex rotunda Thunb, exhibited remarkable inhibition of PRV infection without causing any cytotoxic effects. Specifically, their antiviral selectivity indexes were significantly higher, with values ranging from 6- to 144-fold. The antiviral efficacy of five CHEs was evaluated against other RNA viruses, including PRRSV and PEDV. The extracts showed substantial inhibition of PEDV and PRRSV proliferation. Echinacea and Ilex purpurea Hassk extracts exhibited the highest virus inhibitory effects. To understand the antiviral mechanisms underlying their potent activity, a time-of-addition experiment was conducted. The results indicated that these extracts effectively targeted the early infection and postinfection stages of PRV, PEDV, and PRRSV. The study found that the Chinese herbal extracts, Echinacea and Ilex purpurea Hassk, had both direct and indirect effects on virus particles and cellular targets, demonstrating broad-spectrum antiviral activity against multiple clinical strains of PRV and PEDV. These findings provide a strong foundation for the development of herbal medicines to prevent and treat infections caused by PRV, PEDV and PRRSV in the swine industry. The identified extracts show great promise for the formulation of effective and environmentally friendly antiviral interventions.
Graphical Abstract
... With the use of the commercial Bartha-K61 vaccine since the 1970s, PRV was effectively controlled in Chinese swine farms. However, since 2011, the PRV variant strain was discovered in pigs immunized with the Bartha-K61 vaccine in Northern China, and then spread rapidly almost nationwide [6,7]. The epidemiological investigation revealed that the positive rate of wild-type PRV was 8.27% between 2012 and 2017, and it even reached 12% between 2012 and 2013 [8]. ...
... Although the Bartha-K61 vaccine was widely used in swine farms, more and more outbreaks of PR were reported in vaccinated swine farms since the variant strain was discovered [9][10][11]. Several research studies have shown that the Bartha-K61 vaccine could not provide full protection against the PRV variant strains [7,12,13]. Compared with classical PRV strains, the PRV variant showed stronger pathogenicity in pigs [10,14]. In recent years, several novel vaccines based on PRV variant strains have been developed and evaluated, including the gE/gIdeleted inactivated vaccine based on the PRV ZJ01 strain [15], the inactivated vaccine (gE-deleted) and the live attenuated vaccine (gE/gI/TK-deleted) based on the PRV HN1201 strain [16,17]. ...
... The results of previous studies showed that the gE protein of the PRV variant strain contained two Aspartate (Asp, D) insertions when compared with earlier PRV strains that were isolated from China. Although Asp insertions were also observed in a few early PRV strains, the insertions in the variant strains were highly conserved [7,9]. The results of the amino acid sequence analysis showed that the gE protein of the JS-2020 strain is similar to the earlier Chinese PRV strains without the Asp insertion at the amino acid position 497 ( Figure 4). ...
Pseudorabies virus (PRV) variants were discovered in immunized pigs in Northern China and have become the dominant strains since 2011, which caused huge economic losses. In this study, a classical PRV strain was successfully isolated in a PRV gE positive swine farm. The complete genome sequence was obtained using a high-throughput sequencing method and the virus was named JS-2020. The nucleotide homology analysis and phylogenetic tree based on complete genome sequences or gC gene showed that the JS-2020 strain was relatively close to the classical Ea strain in genotype II clade. However, a large number of amino acid variations occurred in the JS-2020 strain compared with the Ea strain, including multiple immunogenic and virulence-related genes. In particular, the gE protein of JS-2020 was similar to earlier Chinese PRV strains without Aspartate insertion. However, the amino acid variations analysis based on major immunogenic and virulence-related genes showed that the JS-2020 strain was not only homologous with earlier PRV strains, but also with strains isolated in recent years. Moreover, the JS-2020 strain was identified as a recombinant between the GXGG-2016 and HLJ-2013 strains. The pathogenicity analysis proved that the PRV JS-2020 strain has typical neurogenic infections and a strong pathogenicity in mice. Together, a novel recombinant classical strain was isolated and characterized in the context of the PRV variant pandemic in China. This study provided some valuable information for the study of the evolution of PRV in China.
