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Pseudorabies Virus
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Pseudorabies Virus

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 51468

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Yan-Dong Tang

E-Mail Website
Guest Editor
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China
Interests: Pseudorabies virus
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Xiangdong Li

E-Mail Website
Guest Editor
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
Interests: veterinary viruses; pathogenesis; vaccine and diagnostics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pseudorabies virus (PRV) is a herpesvirus of swine, a member of the Alphaherpesvirinae subfamily, and the etiological agent of Aujeszky's disease. PRV is a pathogen of swine resulting in devastating disease and economic losses worldwide. Recently, more and more evidence from the outbreak of PRV variants has indicated that PRV could be transmitted cross-species to infect humans. Therefore, studies focusing on PRV is urgent.

The aim of this Special Issue is to offer a dedicated opportunity for collecting the newest contributions in the field of Pseudorabies virus research, providing new insights and addressing research on unresolved issues. Evolution, viral replication, virus–host interaction, pathogenesis and immunity, gene therapy, viral oncotherapy, and novel antiviral strategies are a just selection of topics relevant to research in the field, which can be contributed to this Special Issue. All researchers working in the field are cordially invited to contribute original research papers or propose reviews to this Special Issue of Viruses.

Dr. Yan-Dong Tang
Prof. Dr. Xiangdong Li 
Guest Editors

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Keywords

  • Pseudorabies virus
  • Viral replication
  • Virus–host interaction
  • Pathogenesis and immunity
  • Novel antiviral strategies

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Published Papers (19 papers)

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14 pages, 2852 KiB  
Article
Serological Investigation and Genetic Characteristics of Pseudorabies Virus between 2019 and 2021 in Henan Province of China
by Ximeng Chen, Hongxuan Li, Qianlei Zhu, Hongying Chen, Zhenya Wang, Lanlan Zheng, Fang Liu and Zhanyong Wei
Viruses 2022, 14(8), 1685; https://doi.org/10.3390/v14081685 - 30 Jul 2022
Cited by 6 | Viewed by 1511
Abstract
In late 2011, severe pseudorabies (PR) outbreaks occurred among swine herds vaccinated with the Bartha-K61 vaccine in many provinces of China, causing enormous economic losses for the pork industry. To understand the epidemic profile and genetic characteristics of the pseudorabies virus (PRV), a [...] Read more.
In late 2011, severe pseudorabies (PR) outbreaks occurred among swine herds vaccinated with the Bartha-K61 vaccine in many provinces of China, causing enormous economic losses for the pork industry. To understand the epidemic profile and genetic characteristics of the pseudorabies virus (PRV), a total of 35,796 serum samples were collected from 1090 pig farms of different breeding scales between 2019 and 2021 in the Henan province where swine had been immunized with the Bartha-K61 vaccine, and PRV glycoprotein E (gE)-specific antibodies were detected using an enzyme-linked immunosorbent assay (ELISA). The results reveal that the overall positive rate for PRV gE antibodies was 20.33% (7276/35,796), which decreased from 25.00% (2596/10,385) in 2019 to 16.69% (2222/13,315) in 2021, demonstrating that PR still existed widely in pig herds in the Henan province but displayed a decreasing trend. Further analysis suggested that the PRV-seropositive rate may be associated with farm size, farm category, quarter, region and the cross-regional transportation of livestock. Moreover, the gE gene complete sequences of 18 PRV isolates were obtained, and they shared a high identity (97.1–100.0%) with reference strains at the nucleotide level. Interestingly, the phylogenetic analysis based on the gE complete sequences found that there were both classical strains and variant strains in pig herds. The deduced amino acid sequence analysis of the gE gene showed that there were unique amino acids in the classical strains, the variant strains and genotype Ⅱ strains. This study provides epidemiological data that could be useful in the prevention of pseudorabies in Henan, China, and this finding contributed to our understanding of the epidemiology and evolution of PRV. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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14 pages, 2823 KiB  
Article
Pseudorabies Virus Tegument Protein UL13 Suppresses RLR-Mediated Antiviral Innate Immunity through Regulating Receptor Transcription
by Ningning Zhao, Fan Wang, Zhengjie Kong and Yingli Shang
Viruses 2022, 14(7), 1465; https://doi.org/10.3390/v14071465 - 2 Jul 2022
Cited by 5 | Viewed by 2289
Abstract
Pseudorabies virus (PRV) has evolved various strategies to escape host antiviral immune responses. However, it remains unclear whether and how PRV-encoded proteins modulate the RIG-I-like receptor (RLR)-mediated signals for immune evasion. Here, we show that the PRV tegument protein UL13 functions as an [...] Read more.
Pseudorabies virus (PRV) has evolved various strategies to escape host antiviral immune responses. However, it remains unclear whether and how PRV-encoded proteins modulate the RIG-I-like receptor (RLR)-mediated signals for immune evasion. Here, we show that the PRV tegument protein UL13 functions as an antagonist of RLR-mediated antiviral responses via suppression of the transcription of RIG-I and MDA5, but not LGP2. UL13 overexpression significantly inhibits both the mRNA and protein levels of RIG-I and MDA5, along with RIG-I- or MDA5-mediated antiviral immune responses, whereas overexpression of RIG-I or MDA5 counteracts such UL13-induced suppression. Mechanistically, UL13 suppresses the expression of RIG-I and MDA5 by inhibiting activation of the transcription factor NF-κB. Consequently, overexpression of p65 promotes the activation of RIG-I and MDA5 promoters. Moreover, deletion of the p65-binding sites in the promoters of RIG-I or MDA5 abolishes the suppression role of UL13. As a result, mutant PRV lacking UL13 elicits stronger host antiviral immune responses than PRV-WT. Hence, our results provide a novel functional role of UL13-induced suppression of host antiviral immunity through modulating receptors’ transcription. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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14 pages, 5898 KiB  
Article
Metabolomics Analysis of PK-15 Cells with Pseudorabies Virus Infection Based on UHPLC-QE-MS
by Panrao Liu, Danhe Hu, Lili Yuan, Zhengmin Lian, Xiaohui Yao, Zhenbang Zhu and Xiangdong Li
Viruses 2022, 14(6), 1158; https://doi.org/10.3390/v14061158 - 27 May 2022
Cited by 2 | Viewed by 1975
Abstract
Viruses depend on the metabolic mechanisms of the host to support viral replication. We utilize an approach based on ultra-high-performance liquid chromatography/Q Exactive HF-X Hybrid Quadrupole-Orbitrap Mass (UHPLC-QE-MS) to analyze the metabolic changes in PK-15 cells induced by the infections of the pseudorabies [...] Read more.
Viruses depend on the metabolic mechanisms of the host to support viral replication. We utilize an approach based on ultra-high-performance liquid chromatography/Q Exactive HF-X Hybrid Quadrupole-Orbitrap Mass (UHPLC-QE-MS) to analyze the metabolic changes in PK-15 cells induced by the infections of the pseudorabies virus (PRV) variant strain and Bartha K61 strain. Infections with PRV markedly changed lots of metabolites, when compared to the uninfected cell group. Additionally, most of the differentially expressed metabolites belonged to glycerophospholipid metabolism, sphingolipid metabolism, purine metabolism, and pyrimidine metabolism. Lipid metabolites account for the highest proportion (around 35%). The results suggest that those alterations may be in favor of virion formation and genome amplification to promote PRV replication. Different PRV strains showed similar results. An understanding of PRV-induced metabolic reprogramming will provide valuable information for further studies on PRV pathogenesis and the development of antiviral therapy strategies. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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14 pages, 3372 KiB  
Article
Histamine Is Responsible for the Neuropathic Itch Induced by the Pseudorabies Virus Variant in a Mouse Model
by Bing Wang, Hongxia Wu, Hansong Qi, Hanglin Li, Li Pan, Lianfeng Li, Kehui Zhang, Mengqi Yuan, Yimin Wang, Hua-Ji Qiu and Yuan Sun
Viruses 2022, 14(5), 1067; https://doi.org/10.3390/v14051067 - 17 May 2022
Cited by 14 | Viewed by 2297
Abstract
Pseudorabies virus (PRV) is the causative agent of pseudorabies (PR). It can infect a wide range of mammals. PRV infection can cause severe acute neuropathy (the so-called “mad itch”) in nonnatural hosts. PRV can infect the peripheral nervous system (PNS), where it can [...] Read more.
Pseudorabies virus (PRV) is the causative agent of pseudorabies (PR). It can infect a wide range of mammals. PRV infection can cause severe acute neuropathy (the so-called “mad itch”) in nonnatural hosts. PRV can infect the peripheral nervous system (PNS), where it can establish a quiescent, latent infection. The dorsal root ganglion (DRG) contains the cell bodies of the spinal sensory neurons, which can transmit peripheral sensory signals, including itch and somatic pain. Little attention has been paid to the underlying mechanism of the itch caused by PRV in nonnatural hosts. In this study, a mouse model of the itch caused by PRV was elaborated. BALB/c mice were infected intramuscularly with 105 TCID50 of PRV TJ. The frequency of the bite bouts and the durations of itch were recorded and quantified. The results showed that the PRV-infected mice developed spontaneous itch at 32 h postinfection (hpi). The frequency of the bite bouts and the durations of itch were increased over time. The mRNA expression levels of the receptors and the potential cation channels that are relevant to the itch-signal transmission in the DRG neurons were quantified. The mRNA expression levels of tachykinin 1 (TAC1), interleukin 2 (IL-2), IL-31, tryptases, tryptophan hydroxylase 1 (TPH1), and histidine decarboxylase (HDC) were also measured by high-throughput RNA sequencing and real-time reverse transcription PCR. The results showed that the mean mRNA level of the HDC in the DRG neurons isolated from the PRV-infected mice was approximately 25-fold higher than that of the controls at 56 hpi. An immunohistochemistry (IHC) was strongly positive for HDC in the DRG neurons of the PRV-infected mice, which led to the high expression of histamine at the injected sites. The itch of the infected mice was inhibited by chlorphenamine hydrogen maleate (an antagonist for the histamine H1 receptor) in a dose-dependent manner. The mRNA and protein levels of the HDC in the DRG neurons were proportional to the severity of the itch induced by different PRV strains. Taken together, the histamine synthesized by the HDC in the DRG neurons was responsible for the PRV-induced itch in the mice. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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14 pages, 3881 KiB  
Article
The Genetic Characterization of a Novel Natural Recombinant Pseudorabies Virus in China
by Jianbo Huang, Wenjie Tang, Xvetao Wang, Jun Zhao, Kenan Peng, Xiangang Sun, Shuwei Li, Shengyao Kuang, Ling Zhu, Yuancheng Zhou and Zhiwen Xu
Viruses 2022, 14(5), 978; https://doi.org/10.3390/v14050978 - 6 May 2022
Cited by 2 | Viewed by 1663
Abstract
We sequenced the complete genome of the pseudorabies virus (PRV) FJ epidemic strain, and we studied the characteristics and the differences compared with the classical Chinese strain and that of other countries. Third-generation sequencing and second-generation sequencing technology were used to construct, sequence, [...] Read more.
We sequenced the complete genome of the pseudorabies virus (PRV) FJ epidemic strain, and we studied the characteristics and the differences compared with the classical Chinese strain and that of other countries. Third-generation sequencing and second-generation sequencing technology were used to construct, sequence, and annotate an efficient, accurate PRV library. The complete FJ genome was 143,703 bp, the G+C content was 73.67%, and it encoded a total of 70 genes. The genetic evolution of the complete genome and some key gene sequences of the FJ strain and PRV reference strains were analyzed by the maximum likelihood (ML) method of MEGA 7.0 software. According to the ML tree based on the full-length genome sequences, PRV FJ strain was assigned to the branch of genotype II, and it showed a close evolutionary relationship with PRV epidemic variants isolated in China after 2011. The gB, gC, gD, gH, gL, gM, gN, TK, gI, and PK genes of the FJ strain were assigned to the same branch with other Chinese epidemic mutants; its gG gene was assigned to the same branch with the classic Chinese Fa and Ea strains; and its gE gene was assigned to a relatively independent branch. Potential recombination events were predicted by the RDP4 software, which showed that the predicted recombination sites were between 1694 and 1936 bp, 101,113 and 102,660 bp, and 107,964 and 111,481 bp in the non-coding region. This result broke the previously reported general rule that pseudorabies virus recombination events occur in the gene coding region. The major backbone strain of the recombination event was HLJ8 and the minor backbone strain was Ea. Our results allowed us to track and to grasp the recent molecular epidemiological changes of PRV. They also provide background materials for the development of new PRV vaccines, and they lay a foundation for further study of PRV. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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15 pages, 3163 KiB  
Article
Pseudorabies Virus ICP0 Abolishes Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Degrading P65
by Xiangbo Zhang, Jingying Xie, Ming Gao, Zhenfang Yan, Lei Chen, Suocheng Wei and Ruofei Feng
Viruses 2022, 14(5), 954; https://doi.org/10.3390/v14050954 - 2 May 2022
Cited by 4 | Viewed by 1718
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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10 pages, 466 KiB  
Article
Epidemiological Investigation and Genetic Analysis of Pseudorabies Virus in Yunnan Province of China from 2017 to 2021
by Jun Yao, Juan Li, Lin Gao, Yuwen He, Jiarui Xie, Pei Zhu, Ying Zhang, Xue Zhang, Luoyan Duan, Shibiao Yang, Chunlian Song and Xianghua Shu
Viruses 2022, 14(5), 895; https://doi.org/10.3390/v14050895 - 25 Apr 2022
Cited by 9 | Viewed by 1825
Abstract
In recent years, the prevalence of pseudorabies virus (PRV) has caused huge economic losses to the Chinese pig industry. Meanwhile, PRV infection in humans also sounded the alarm about its cross-species transmission from pigs to humans. To study the regional PRV epidemic, serological [...] Read more.
In recent years, the prevalence of pseudorabies virus (PRV) has caused huge economic losses to the Chinese pig industry. Meanwhile, PRV infection in humans also sounded the alarm about its cross-species transmission from pigs to humans. To study the regional PRV epidemic, serological and epidemiological investigations of PRV in pig populations from Yunnan Province during 2017–2021 were performed. The results showed that 31.37% (6324/20,158, 95% CI 30.73–32.01) of serum samples were positive for PRV glycoprotein E (gE)-specific antibodies via enzyme-linked immunosorbent assay (ELISA). The risk factors, including the breeding scale and development stage, were significantly associated with PRV seroprevalence among pigs in Yunnan Province. Of the 416 tissue samples collected from PRV-suspected pigs in Yunnan Province, 43 (10.33%, 95% CI 7.41–13.26) samples were positive for PRV-gE nucleic acid in which 15 novel PRV strains from these PRV-positive samples were isolated, whose gC and gE sequences were analyzed. Phylogenetic analysis showed that all 15 isolates obtained in this study belonged to the genotype II. Additionally, the gC gene of one isolate (YuN-YL-2017) was genetically closer to variant PRV strains compared with others, while the gE gene was in the same clade with other classical PRV strains, indicating that this isolate might be a recombinant strain generated from the classical and variant strains. The results revealed the severe PRV epidemic in Yunnan Province and indicated that PRV variants are the major genotypes threatening the pig industry development. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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11 pages, 1958 KiB  
Article
A Nectin1 Mutant Mouse Model Is Resistant to Pseudorabies Virus Infection
by Xiaohui Yang, Chuanzhao Yu, Qiuyan Zhang, Linjun Hong, Ting Gu, Enqin Zheng, Zheng Xu, Zicong Li, Changxu Song, Gengyuan Cai, Zhenfang Wu and Huaqiang Yang
Viruses 2022, 14(5), 874; https://doi.org/10.3390/v14050874 - 22 Apr 2022
Cited by 3 | Viewed by 1596
Abstract
The present study generated nectin1-mutant mice with single amino acid substitution and tested the anti-pseudorabies virus (PRV) ability of the mutant mice, with the aim to establish a model for PRV-resistant livestock. A phenylalanine to alanine transition at position 129 (F129A) of nectin1 [...] Read more.
The present study generated nectin1-mutant mice with single amino acid substitution and tested the anti-pseudorabies virus (PRV) ability of the mutant mice, with the aim to establish a model for PRV-resistant livestock. A phenylalanine to alanine transition at position 129 (F129A) of nectin1 was introduced into the mouse genome to generate nectin1 (F129A) mutant mice. The mutant mice were infected with a field-isolated highly virulent PRV strain by subcutaneous injection of virus. We found that the homozygous mutant mice had significantly alleviated disease manifestations and decreased death rate and viral loading in serum and tissue compared with heterozygous mutant and wild-type mice. In addition to disease resistance, the homozygous mutant mice showed a defect in eye development, indicating the side effect on animals by only one amino acid substitution in nectin1. Results demonstrate that gene modification in nectin1 is an effective approach to confer PRV resistance on animals, but the mutagenesis pattern requires further investigation to increase viral resistance without negative effect on animal development. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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15 pages, 2521 KiB  
Article
Proteomic Analysis of Vero Cells Infected with Pseudorabies Virus
by Xintan Yang, Shengkui Xu, Dengjin Chen, Ruijiao Jiang, Haoran Kang, Xinna Ge, Lei Zhou, Jun Han, Yongning Zhang, Xin Guo and Hanchun Yang
Viruses 2022, 14(4), 755; https://doi.org/10.3390/v14040755 - 4 Apr 2022
Cited by 2 | Viewed by 2128
Abstract
Suid herpesvirus 1 (SuHV-1), known as pseudorabies virus (PRV), is one of the most devastating swine pathogens in China, particularly the sudden occurrence of PRV variants in 2011. The higher pathogenicity and cross-species transmission potential of the newly emerged variants caused not only [...] Read more.
Suid herpesvirus 1 (SuHV-1), known as pseudorabies virus (PRV), is one of the most devastating swine pathogens in China, particularly the sudden occurrence of PRV variants in 2011. The higher pathogenicity and cross-species transmission potential of the newly emerged variants caused not only colossal economic losses, but also threatened public health. To uncover the underlying pathogenesis of PRV variants, Tandem Mass Tag (TMT)-based proteomic analysis was performed to quantitatively screen the differentially expressed cellular proteins in PRV-infected Vero cells. A total of 7072 proteins were identified and 960 proteins were significantly regulated: specifically 89 upregulated and 871 downregulated. To make it more credible, the expression of XRCC5 and XRCC6 was verified by western blot and RT-qPCR, and the results dovetailed with the proteomic data. The differentially expressed proteins were involved in various biological processes and signaling pathways, such as chaperonin-containing T-complex, NIK/NF-κB signaling pathway, DNA damage response, and negative regulation of G2/M transition of mitotic cell cycle. Taken together, our data holistically outline the interactions between PRV and host cells, and our results may shed light on the pathogenesis of PRV variants and provide clues for pseudorabies prevention. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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15 pages, 4106 KiB  
Article
Huaier Polysaccharide Interrupts PRV Infection via Reducing Virus Adsorption and Entry
by Changchao Huan, Jingting Yao, Weiyin Xu, Wei Zhang, Ziyan Zhou, Haochun Pan and Song Gao
Viruses 2022, 14(4), 745; https://doi.org/10.3390/v14040745 - 1 Apr 2022
Cited by 6 | Viewed by 2060
Abstract
A pseudorabies virus (PRV) novel virulent variant outbreak occurred in China in 2011. However, little is known about PRV prevention and treatment. Huaier polysaccharide has been used to treat some solid cancers, although its antiviral activity has not been reported. Our study confirmed [...] Read more.
A pseudorabies virus (PRV) novel virulent variant outbreak occurred in China in 2011. However, little is known about PRV prevention and treatment. Huaier polysaccharide has been used to treat some solid cancers, although its antiviral activity has not been reported. Our study confirmed that the polysaccharide can effectively inhibit infection of PRV XJ5 in PK15 cells. It acted in a dose-dependent manner when blocking virus adsorption and entry into PK15 cells. Moreover, it suppressed PRV replication in PK15 cells. In addition, the results suggest that Huaier polysaccharide plays a role in treating PRV XJ5 infection by directly inactivating PRV XJ5. In conclusion, Huaier polysaccharide might be a novel therapeutic agent for preventing and controlling PRV infection. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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14 pages, 5397 KiB  
Article
Isolation and Characterization of Two Pseudorabies Virus and Evaluation of Their Effects on Host Natural Immune Responses and Pathogenicity
by Qiongqiong Zhou, Longfeng Zhang, Hongyang Liu, Guangqiang Ye, Li Huang and Changjiang Weng
Viruses 2022, 14(4), 712; https://doi.org/10.3390/v14040712 - 29 Mar 2022
Cited by 6 | Viewed by 1937
Abstract
Pseudorabies, caused by the pseudorabies virus (PRV), is an acute fatal disease, which can infect rodents, mammals, and other livestock and wild animals across species. Recently, the emergence of PRV virulent isolates indicates a high risk of a variant PRV epidemic and the [...] Read more.
Pseudorabies, caused by the pseudorabies virus (PRV), is an acute fatal disease, which can infect rodents, mammals, and other livestock and wild animals across species. Recently, the emergence of PRV virulent isolates indicates a high risk of a variant PRV epidemic and the need for continuous surveillance. In this study, PRV-GD and PRV-JM, two fatal PRV variants, were isolated and their pathogenicity as well as their effects on host natural immune responses were assessed. PRV-GD and PRV-JM were genetically closest to PRV variants currently circulating in Heilongjiang (HLJ8) and Jiangxi (JX/CH/2016), which belong to genotype 2.2. Consistently, antisera from sows immunized with PRV-Ea classical vaccination showed much lower neutralization ability to PRV-GD and PRV-JM. However, the antisera from the pigs infected with PRV-JM had an extremely higher neutralization ability to PRV-TJ (as a positive control), PRV-GD and PRV-JM. In vivo, PRV-GD and PRV-JM infections caused 100% death in mice and piglets and induced extensive tissue damage, cell death, and inflammatory cytokine release. Our analysis of the emergence of PRV variants indicate that pigs immunized with the classical PRV vaccine are incapable of providing sufficient protection against these PRV isolates, and there is a risk of continuous evolution and virulence enhancement. Efforts are still needed to conduct epidemiological monitoring for the PRV and to develop novel vaccines against this emerging and reemerging infectious disease. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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12 pages, 5804 KiB  
Article
Generation of Premature Termination Codon (PTC)-Harboring Pseudorabies Virus (PRV) via Genetic Code Expansion Technology
by Tong-Yun Wang, Guo-Ju Sang, Qian Wang, Chao-Liang Leng, Zhi-Jun Tian, Jin-Mei Peng, Shu-Jie Wang, Ming-Xia Sun, Fan-Dan Meng, Hao Zheng, Xue-Hui Cai and Yan-Dong Tang
Viruses 2022, 14(3), 572; https://doi.org/10.3390/v14030572 - 10 Mar 2022
Cited by 8 | Viewed by 2574
Abstract
Despite many efforts and diverse approaches, developing an effective herpesvirus vaccine remains a great challenge. Traditional inactivated and live-attenuated vaccines always raise efficacy or safety concerns. This study used Pseudorabies virus (PRV), a swine herpes virus, as a model. We attempted to develop [...] Read more.
Despite many efforts and diverse approaches, developing an effective herpesvirus vaccine remains a great challenge. Traditional inactivated and live-attenuated vaccines always raise efficacy or safety concerns. This study used Pseudorabies virus (PRV), a swine herpes virus, as a model. We attempted to develop a live but replication-incompetent PRV by genetic code expansion (GCE) technology. Premature termination codon (PTC) harboring PRV was successfully rescued in the presence of orthogonal system MbpylRS/tRNAPyl pair and unnatural amino acids (UAA). However, UAA incorporating efficacy seemed extremely low in our engineered PRV PTC virus. Furthermore, we failed to establish a stable transgenic cell line containing orthogonal translation machinery for PTC virus replication, and we demonstrated that orthogonal tRNAPyl is a key limiting factor. This study is the first to demonstrate that orthogonal translation system-mediated amber codon suppression strategy could precisely control PRV-PTC engineered virus replication. To our knowledge, this is the first reported PTC herpesvirus generated by GCE technology. Our work provides a proof-of-concept for generating UAAs-controlled PRV-PTC virus, which can be used as a safe and effective vaccine. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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14 pages, 3853 KiB  
Article
Pseudorabies Virus Inhibits Expression of Liver X Receptors to Assist Viral Infection
by Yi Wang, Guo-Li Li, Yan-Li Qi, Li-Yun Li, Lu-Fang Wang, Cong-Rong Wang, Xin-Rui Niu, Tao-Xue Liu, Jiang Wang, Guo-Yu Yang, Lei Zeng and Bei-Bei Chu
Viruses 2022, 14(3), 514; https://doi.org/10.3390/v14030514 - 3 Mar 2022
Cited by 9 | Viewed by 2858
Abstract
Pseudorabies virus (PRV) is a contagious herpesvirus that causes Aujeszky’s disease and economic losses worldwide. Liver X receptors (LXRs) belong to the nuclear receptor superfamily and are critical for the control of lipid homeostasis. However, the role of LXR in PRV infection has [...] Read more.
Pseudorabies virus (PRV) is a contagious herpesvirus that causes Aujeszky’s disease and economic losses worldwide. Liver X receptors (LXRs) belong to the nuclear receptor superfamily and are critical for the control of lipid homeostasis. However, the role of LXR in PRV infection has not been fully established. In this study, we found that PRV infection downregulated the mRNA and protein levels of LXRα and LXRβ in vitro and in vivo. Furthermore, we discovered that LXR activation suppressed PRV proliferation, while LXR inhibition promoted PRV proliferation. We demonstrated that LXR activation-mediated reduction of cellular cholesterol was critical for the dynamics of PRV entry-dependent clathrin-coated pits. Replenishment of cholesterol restored the dynamics of clathrin-coated pits and PRV entry under LXR activation conditions. Interestingly, T0901317, an LXR agonist, prevented PRV infection in mice. Our results support a model that PRV modulates LXR-regulated cholesterol metabolism to facilitate viral proliferation. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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Review

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27 pages, 2295 KiB  
Review
Pseudorabies Virus: From Pathogenesis to Prevention Strategies
by Hui-Hua Zheng, Peng-Fei Fu, Hong-Ying Chen and Zhen-Ya Wang
Viruses 2022, 14(8), 1638; https://doi.org/10.3390/v14081638 - 27 Jul 2022
Cited by 31 | Viewed by 7031
Abstract
Pseudorabies (PR), also called Aujeszky’s disease (AD), is a highly infectious viral disease which is caused by pseudorabies virus (PRV). It has been nearly 200 years since the first PR case occurred. Currently, the virus can infect human beings and various mammals, including [...] Read more.
Pseudorabies (PR), also called Aujeszky’s disease (AD), is a highly infectious viral disease which is caused by pseudorabies virus (PRV). It has been nearly 200 years since the first PR case occurred. Currently, the virus can infect human beings and various mammals, including pigs, sheep, dogs, rabbits, rodents, cattle and cats, and among them, pigs are the only natural host of PRV infection. PRV is characterized by reproductive failure in pregnant sows, nervous disorders in newborn piglets, and respiratory distress in growing pigs, resulting in serious economic losses to the pig industry worldwide. Due to the extensive application of the attenuated vaccine containing the Bartha-K61 strain, PR was well controlled. With the variation of PRV strain, PR re-emerged and rapidly spread in some countries, especially China. Although researchers have been committed to the design of diagnostic methods and the development of vaccines in recent years, PR is still an important infectious disease and is widely prevalent in the global pig industry. In this review, we introduce the structural composition and life cycle of PRV virions and then discuss the latest findings on PRV pathogenesis, following the molecular characteristic of PRV and the summary of existing diagnosis methods. Subsequently, we also focus on the latest clinical progress in the prevention and control of PRV infection via the development of vaccines, traditional herbal medicines and novel small RNAs. Lastly, we provide an outlook on PRV eradication. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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15 pages, 709 KiB  
Review
The Epidemiology and Variation in Pseudorabies Virus: A Continuing Challenge to Pigs and Humans
by Qingyun Liu, Yan Kuang, Yafei Li, Huihui Guo, Chuyue Zhou, Shibang Guo, Chen Tan, Bin Wu, Huanchun Chen and Xiangru Wang
Viruses 2022, 14(7), 1463; https://doi.org/10.3390/v14071463 - 1 Jul 2022
Cited by 19 | Viewed by 4243
Abstract
Pseudorabies virus (PRV) can infect most mammals and is well known for causing substantial economic losses in the pig industry. In addition to pigs, PRV infection usually leads to severe itching, central nervous system dysfunction, and 100% mortality in its non-natural hosts. It [...] Read more.
Pseudorabies virus (PRV) can infect most mammals and is well known for causing substantial economic losses in the pig industry. In addition to pigs, PRV infection usually leads to severe itching, central nervous system dysfunction, and 100% mortality in its non-natural hosts. It should be noted that increasing human cases of PRV infection have been reported in China since 2017, and these patients have generally suffered from nervous system damage and even death. Here, we reviewed the current prevalence and variation in PRV worldwide as well as the PRV-caused infections in animals and humans, and briefly summarized the vaccines and diagnostic methods used for pseudorabies control. Most countries, including China, have control programs in place for pseudorabies in domestic pigs, and thus, the disease is on the decline; however, PRV is still globally epizootic and an important pathogen for pigs. In countries where pseudorabies in domestic pigs have already been eliminated, the risk of PRV transmission by infected wild animals should be estimated and prevented. As a member of the alphaherpesviruses, PRV showed protein-coding variation that was relatively higher than that of herpes simplex virus-1 (HSV-1) and varicella-zoster virus (VZV), and its evolution was mainly contributed to by the frequent recombination observed between different genotypes or within the clade. Recombination events have promoted the generation of new variants, such as the variant strains resulting in the outbreak of pseudorabies in pigs in China, 2011. There have been 25 cases of PRV infections in humans reported in China since 2017, and they were considered to be infected by PRV variant strains. Although PRV infections have been sporadically reported in humans, their causal association remains to be determined. This review provided the latest epidemiological information on PRV for the better understanding, prevention, and treatment of pseudorabies. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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15 pages, 770 KiB  
Review
A Comparison of Pseudorabies Virus Latency to Other α-Herpesvirinae Subfamily Members
by Jing Chen, Gang Li, Chao Wan, Yixuan Li, Lianci Peng, Rendong Fang, Yuanyi Peng and Chao Ye
Viruses 2022, 14(7), 1386; https://doi.org/10.3390/v14071386 - 24 Jun 2022
Cited by 5 | Viewed by 2163
Abstract
Pseudorabies virus (PRV), the causative agent of Aujeszky’s disease, is one of the most important infectious pathogens threatening the global pig industry. Like other members of alphaherpesviruses, PRV establishes a lifelong latent infection and occasionally reactivates from latency after stress stimulus in infected [...] Read more.
Pseudorabies virus (PRV), the causative agent of Aujeszky’s disease, is one of the most important infectious pathogens threatening the global pig industry. Like other members of alphaherpesviruses, PRV establishes a lifelong latent infection and occasionally reactivates from latency after stress stimulus in infected pigs. Latent infected pigs can then serve as the source of recurrent infection, which is one of the difficulties for PRV eradication. Virus latency refers to the retention of viral complete genomes without production of infectious progeny virus; however, following stress stimulus, the virus can be reactivated into lytic infection, which is known as the latency-reactivation cycle. Recently, several research have indicated that alphaherpesvirus latency and reactivation is regulated by a complex interplay between virus, neurons, and the immune system. However, with those limited reports, the relevant advances in PRV latency are lagging behind. Therefore, in this review we focus on the regulatory mechanisms in PRV latency via summarizing the progress of PRV itself and that of other alphaherpesviruses, which will improve our understanding in the underlying mechanism of PRV latency and help design novel therapeutic strategies to control PRV latency. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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12 pages, 556 KiB  
Review
The Role of Latency-Associated Transcripts in the Latent Infection of Pseudorabies Virus
by Jiahuan Deng, Zhuoyun Wu, Jiaqi Liu, Qiuyun Ji and Chunmei Ju
Viruses 2022, 14(7), 1379; https://doi.org/10.3390/v14071379 - 24 Jun 2022
Cited by 6 | Viewed by 1852
Abstract
Pseudorabies virus (PRV) can cause neurological, respiratory, and reproductive diseases in pigs and establish lifelong latent infection in the peripheral nervous system (PNS). Latent infection is a typical feature of PRV, which brings great difficulties to the prevention, control, and eradication of pseudorabies. [...] Read more.
Pseudorabies virus (PRV) can cause neurological, respiratory, and reproductive diseases in pigs and establish lifelong latent infection in the peripheral nervous system (PNS). Latent infection is a typical feature of PRV, which brings great difficulties to the prevention, control, and eradication of pseudorabies. The integral mechanism of latent infection is still unclear. Latency-associated transcripts (LAT) gene is the only transcriptional region during latent infection of PRV which plays the key role in regulating viral latent infection and inhibiting apoptosis. Here, we review the characteristics of PRV latent infection and the transcriptional characteristics of the LAT gene. We also analyzed the function of non-coding RNA (ncRNA) produced by the LAT gene and its importance in latent infection. Furthermore, we provided possible strategies to solve the problem of latent infection of virulent PRV strains in the host. In short, the detailed mechanism of PRV latent infection needs to be further studied and elucidated. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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15 pages, 1613 KiB  
Review
A Review of Pseudorabies Virus Variants: Genomics, Vaccination, Transmission, and Zoonotic Potential
by Zongyi Bo and Xiangdong Li
Viruses 2022, 14(5), 1003; https://doi.org/10.3390/v14051003 - 9 May 2022
Cited by 20 | Viewed by 3442
Abstract
Pseudorabies virus (PRV), the causative agent of Aujeszky’s disease, has a broad host range including most mammals and avian species. In 2011, a PRV variant emerged in many Bartha K61-vaccinated pig herds in China and has attracted more and more attention due to [...] Read more.
Pseudorabies virus (PRV), the causative agent of Aujeszky’s disease, has a broad host range including most mammals and avian species. In 2011, a PRV variant emerged in many Bartha K61-vaccinated pig herds in China and has attracted more and more attention due to its serious threat to domestic and wild animals, and even human beings. The PRV variant has been spreading in China for more than 10 years, and considerable research progresses about its molecular biology, pathogenesis, transmission, and host–virus interactions have been made. This review is mainly organized into four sections including outbreak and genomic evolution characteristics of PRV variants, progresses of PRV variant vaccine development, the pathogenicity and transmission of PRV variants among different species of animals, and the zoonotic potential of PRV variants. Considering PRV has caused a huge economic loss of animals and is a potential threat to public health, it is necessary to extensively explore the mechanisms involved in its replication, pathogenesis, and transmission in order to ultimately eradicate it in China. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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18 pages, 1057 KiB  
Review
A Tug of War: Pseudorabies Virus and Host Antiviral Innate Immunity
by Guangqiang Ye, Hongyang Liu, Qiongqiong Zhou, Xiaohong Liu, Li Huang and Changjiang Weng
Viruses 2022, 14(3), 547; https://doi.org/10.3390/v14030547 - 6 Mar 2022
Cited by 19 | Viewed by 3563
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. [...] Read more.
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. Full article
(This article belongs to the Special Issue Pseudorabies Virus)
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