Pseudorabies Research Articles

PRRSV-2 nsp2 Ignites NLRP3 inflammasome through IKKβ-dependent dispersed trans-Golgi network translocation.

The NLRP3 inflammasome is a fundamental component of the innate immune system, yet its excessive activation is intricately associated with viral pathogenesis. Porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2), belonging to the family Arteriviridae, triggers dysregulated cytokine release and interstitial pneumonia, which can quickly escalate to acute respiratory distress and death. However, a mechanistic understanding of PRRSV-2 progression remains unclear. Here, we screen that PRRSV-2 nsp2 activates the NLRP3 inflammasome, thereby instigating a state of hyperinflammation. Mechanistically, PRRSV-2 nsp2 interacts with the nucleotide-binding and oligomerization (NACHT) domain of NLRP3, augmenting IKKβ recruitment to driving NLRP3 translocation to the dispersed trans-Golgi network (dTGN) for oligomerization. This process facilitates ASC polymerization, culminating in the activation of the NLRP3 inflammasome. In addition, the IKKβ-dependent NLRP3 translocation to the dTGN is pivotal for pseudorabies virus (PRV) and encephalomyocarditis virus (EMCV)-induced inflammatory responses. Collectively, these results elucidate a novel mechanism of NLRP3 inflammasome activation during PRRSV-2 infection, providing valuable insights into PRRSV-2 pathogenesis.

Distinct effects of glucocorticoid on pseudorabies virus infection in neuron-like and epithelial cells.

Pseudorabies virus (PRV) is a porcine neurotropic alphaherpesvirus that infects peripheral tissues of its host, spreads into the nervous system, and establishes a life-long latency in neuronal cells. During productive infection, PRV replicates rapidly and causes pseudorabies or Aujeszky's disease. Reactivation from latent infection in the nervous system may lead to anterograde axonal transport of progeny virions, leading to recurrent infection of the epithelial layer and virus spread. Dexamethasone (DEX), a member of the glucocorticoid family that is widely used in clinical treatment as a high-efficiency glucocorticoid receptor (GR) agonist, is known to trigger reactivation of alphaherpesviruses like PRV and the closely related bovine alphaherpesvirus 1. In the current study, two cell type-dependent distinct regulatory mechanisms of glucocorticoid during PRV infection are described. In neuron-like cells, DEX upregulates expression of PRV IE180 and promotes viral productive infection. In addition, we found that GR activates the IE180 promoter by binding multiple GR response elements. The amino acids A465, P631, and I634 in GR were found to be critical for IE180 promoter activation. The impact of DEX on PRV productive infection in epithelial cells was also investigated. Interestingly, DEX was found to downregulate IE180 expression and suppress PRV infection in epithelial cells. Mechanistically, in epithelial cells, activation of the IE180 promoter by the VP16/Oct-1 (octamer-binding transcription factor 1) complex was suppressed by DEX-mediated degradation of Oct-1 in epithelial cells. In summary, our work reveals two distinct, cell type-dependent biological functions of glucocorticoid during PRV infection in neuron-like and epithelial cells, respectively.IMPORTANCEPseudorabies virus (PRV) can infect mucosal epithelium and the peripheral nervous system of its host, resulting in acute infection in epithelial cells and neuronal cells. In this study, we describe that glucocorticoid promotes PRV replication in neuron-like cells while it suppresses productive infection in epithelial cells through distinct regulations of the viral transactivator IE180, thereby revealing a cell type-dependent regulatory mechanism of glucocorticoid on PRV infection. Therefore, our findings provide a new perspective on the role of glucocorticoids during PRV infection.

Pseudorabies virus infection triggers pUL46-mediated phosphorylation of connexin-43 and closure of gap junctions to promote intercellular virus spread.

Gap junctions (GJs) play a pivotal role in intercellular communication between eukaryotic cells, including transfer of biomolecules that contribute to the innate and adaptive immune response. However, if and how viruses affect gap junction intercellular communication (GJIC) remains largely unexplored. Here, we describe how the alphaherpesvirus pseudorabies virus (PRV) triggers ERK1/2-mediated phosphorylation of the main gap junction component connexin 43 (Cx43) and closure of GJIC, which depends on the viral protein pUL46. Consequently, a UL46null PRV mutant is unable to phosphorylate Cx43 or inhibit GJIC and displays reduced intercellular spread, which is effectively rescued by pharmacological inhibition of GJIC. Intercellular spread of UL46null PRV is also rescued by inhibition of the stimulator of interferon genes (STING), suggesting that pUL46-mediated suppression of GJIC contributes to intercellular virus spread by hindering intercellular communication that activates STING. The current study identifies key viral and cellular proteins involved in alphaherpesvirus-mediated suppression of GJIC and reveals that GJIC inhibition enhances virus intercellular spread, thereby opening new avenues for the design of targeted antiviral therapies.

Monitoring of Selected Swine Viral Diseases in Peruvian Amazon Peccaries.

Peccaries (collared peccary-CP-and white-lipped peccary-WLP) are an essential source of protein and income for rural communities in the Amazon region. Since 1980s, researchers in the Amazon have reported recurrent local disappearances of WLP populations. Although such disappearances impact the species conservation and the food security of rural societies, no studies have drawn consistent conclusions about the causes of these population collapses. However, it has recently been proposed that the overabundance of this species before its decline would be related to infectious disease outbreaks. In the current study, we aimed to determine the circulation (occurrence and exposure) of viruses relevant to swine health in CP and WLP populations, namely classical swine fever virus (CSFV), Aujeszky's disease virus (ADV), swine vesicular disease virus (SVDV), and porcine circoviruses (PCV). The study was conducted in two areas of the northeastern Peruvian Amazon: the Yavarí-Mirín River basin (2008 -2020), where WLPs experienced extreme population fluctuations, and the Pucacuro National Reserve (2012-2014), where no WLP disappearances have been reported. Since WLP is not easily found during population declines, we also sampled CP as an indicator of virus circulation in the area as they are likely to be susceptible to the same pathogens. CSFV and ADV antibodies were detected in both peccary species and both areas. Diseases caused by CSFV and ADV have the potential to act as ultimate causes of population collapse, especially in large WLP populations where overabundance could increase the rate of pathogen transmission. Our results were inconclusive in establishing whether or not these viruses drove the WLP population to collapse, but their potential role warrants deeper investigation, expanding the geographical coverage of studies on infectious diseases in peccaries.

The pseudorabies virus UL13 protein kinase triggers phosphorylation of the RNA demethylase FTO, which is associated with FTO-dependent suppression of interferon-stimulated gene expression.

Alpha-ketoglutarate-dependent dioxygenase, also known as fat mass and obesity-associated protein (FTO), is an RNA demethylase that mediates the demethylation of N6,2-O-dimethyladenosine (m6Am) and N6-methyladenosine (m6A). Both m6Am and m6A are prevalent modifications in mRNA and affect different aspects of transcript biology, including splicing, nuclear export, translation efficiency, and degradation. The role of FTO during (herpes) virus infection remains largely unexplored. In this study, we show that the UL13 protein kinase of the alphaherpesvirus pseudorabies virus (PRV) triggers phosphorylation of FTO. In primary epithelial cells, depletion of FTO leads to increased expression of antiviral interferon-stimulated genes (ISGs) and UL13 triggers FTO-dependent suppression of ISG expression. Although PRV infection suppresses m6Am levels in host small nuclear RNA, this is independent of UL13. The current data highlight FTO as an important regulator of antiviral ISG expression and suggest that UL13-mediated phosphorylation of FTO may serve as a previously unrecognized viral strategy to suppress the antiviral interferon response.IMPORTANCERNA modification pathways play important roles in diverse cellular processes and virus life cycles. Although previous studies have demonstrated that alphaherpesviruses can substantially influence cellular RNA modifications, such as m6A, the impact on the m6Am epitranscriptome machinery remains largely unexplored. The present work reports that the UL13 protein kinase of pseudorabies virus (PRV), an alphaherpesvirus, mediates phosphorylation of the m6Am/m6A eraser FTO and that this correlates with a UL13- and FTO-dependent suppression of antiviral interferon-stimulated gene (ISG) expression. Furthermore, PRV infection leads to a pronounced reduction in m6Am levels in host snRNA and also induces phosphorylation of the m6Am writer PCIF1. These data highlight FTO as an important regulator of ISG expression and reveal that viral manipulation of FTO, such as UL13-induced phosphorylation of FTO, may serve as a previously unrecognized interferon evasion strategy.

Genome Characterization of Mammalian Orthoreovirus and Porcine Epidemic Diarrhea Virus Isolated from the Same Fattening Pig.

In 2020, severe diarrhea occurred in four-month-old fattening pigs from nine farms in Shandong Province, China. Fecal samples were collected from diseased pigs and tested by PCR for the presence of mammalian orthoreovirus (MRV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), porcine rotavirus A (PoRVA), transmissible gastroenteritis virus (TGEV), porcine kobuvirus (PKV), and pseudorabies virus (PRV). The viral RNA of MRV and PEDV was detected in the fecal samples. The genome sequences of MRV and PEDV were successfully amplified from the same fecal sample. Genomic and phylogenetic analysis showed that the MRV isolate named MRV2-SD/2020 belongs to serotype 2 MRV (MRV2) and may originate from the reassortment of human and porcine MRVs. Compared with other MRV2 strains, there were four other unique amino acid mutations (L274I, F302L, V347I, and T440M) in the receptor binding region. For the PEDV isolate named PEDV-SD/2020, the nearly complete genome was amplified from the positive fecal samples. Phylogenetic analysis showed that it was classified into the G2a genotype. Compared with CV777 and other PEDV variant strains, its spike (S) protein exhibited two unique mutations (S663T and L966M). This study first reports the co-infection of PEDV and MRV2 in the pigs and provides a new direction for the prevention and control of the diarrhea diseases.

TLR Agonist Immunoadjuvants Provide Effective Protection Against PCV2 and PRV Infections in a Bivalent Subunit Vaccine for PCV2 and PRV.

Diseases associated with porcine circovirus type 2 (PCV2) and pseudorabies virus (PRV) significantly affect the economy of pig farms, particularly when combined infections lead to bacterial co-infections. Antigens from the pseudorabies variant strain gB and gD proteins and PCV2 (genotyped) Cap protein were mixed with the pattern recognition receptor (PRR) agonist FLICd as adjuvants and formulated with a micro-hydrogel adjuvant into PCV2 and PRV bivalent subunit vaccines. Twenty pigs, aged 30-35 days, were divided into groups A (received bivalent subunit vaccine) and B (received bivalent subunit vaccines with recombinant FLICd adjuvant), as well as C (non-vaccinated challenge control) and D (blank control). Groups A and B showed no significant difference in average daily weight gain compared to the unvaccinated controls. Fourteen days post-second vaccination, groups A and B exhibited significantly higher levels of PRV and PCV2 antibodies than groups C and D. Group B showed significantly higher average titers of PRV-specific neutralizing antibodies than group A. Fourteen days post-second vaccination, a PRV (ZJM-1 strain) challenge test was conducted. The vaccinated group achieved 100% protection. Vaccination effectively reduced virus load post-challenge and shortened the PRV shedding period. Vaccination with PCV2 and PRV bivalent subunit vaccines effectively prevents the onset of PCV2-related diseases and infections by wild pseudorabies strains.

Inhibition of the canonical Wnt/β-catenin pathway interferes with macropinocytosis to suppress pseudorabies virus proliferation.

Pseudorabies virus (PRV) is one of the highly contagious pathogens causing significant economic losses to the swine industry worldwide. More importantly, PRV is becoming a potential "life-threatening zoonosis" since the human-originated PRV strain was first isolated in 2019. Previously we found that the canonical Wnt/β-catenin pathway facilitates PRV proliferation, while the underlying mechanism remains unknown. In this study, the antiviral activities of the Wnt inhibitors (Adavivint, CCT251545, FH535, and iCRT14) were identified. Applying these inhibitors significantly inhibited PRV proliferation in different cell lines. Among them, CCT251545 presented the strongest anti-PRV activity with IC50 values less than 200 nM. Our in vivo studies showed that treatment with CCT251545 remarkedly decreased the viral loads and protected mice challenged with PRV. Further study found that CCT251545 neither had a virucidal effect nor affected viral adsorption while mainly interfering with the entry process of the PRV life cycle. Using the FITC-dextran uptake assay, we found that CCT251545 inhibited macropinocytosis. The formation of membrane protrusions, which is important for macropinocytosis, was also inhibited by CCT251545. Consistent with this, knockout of β-catenin suppressed the PRV macropinocytosis and the formation of protrusions. On the contrary, LiCl treatment significantly stimulated the protrusion formation and the PRV entry. Together, these findings suggest that suppression of the Wnt/β-catenin pathway inhibits the macropinocytosis-dependent entry of PRV, thereby providing potential targets for developing antiviral agents against PRV.

Inhibiting UGCG prevents PRV infection by decreasing lysosome-associated autophage

Glucosylceramide synthase (UGCG) is a key enzyme that catalyzes the initial glycosylation step in the biosynthesis of glycosphingolipids (GSLs) derived from glucosylceramide. UGCG is closely associated with various cellular processes, including the cell cycle, angiogenesis, multidrug resistance, and pathogen invasion. In this study, a short hairpin RNA (shRNA) library designed to target key genes involved in the sphingolipid metabolic pathway was utilized to elucidate their roles in Pseudorabies Virus (PRV). Those findings confirm a significant association between sphingolipid metabolism and PRV infection. In addition, this study demonstrated that the knockdown UGCG expression or inhibition of its activity significantly suppresses PRV infection. This suppression is accompanied by reduced expression of autophagy-related proteins that are induced by PRV infection, blockade of autophagic flux, and significant activation of the STING signaling pathway induced by PRV infection. Through extensive investigation, this research revealed that inhibition of UGCG affects the expression of lysosome-associated proteins, alters the lysosomal pH, disrupts lysosomal homeostasis, and impedes autophagolysosomal degradation. Additionally, UGCG inhibition influences the conversion of light chain 3-II (LC3-II) and the formation of LC3-STING complexes, negatively regulates the autophagic degradation of STING, and ensures sustained activation of the PRV-induced STING signaling pathway, thereby achieving resistance against PRV infection. Finally, through in vivo evaluation, this study revealed that UGCG inhibitors, Eliglustat hemitartrate and Ibiglustat, hold promise as potential therapeutics for the treatment of PRV infection. In summary, this study preliminarily elucidates the impact of UGCG on PRV infection and its associated molecular mechanisms, suggesting UGCG could serve as a potential novel target for the prevention and treatment of viral diseases such as PRV.

MDV-encoded protein kinase US3 phosphorylates WTAP to inhibit transcriptomic m6A modification and cellular protein translation

Marek’s disease virus (MDV)-encoded US3 is a highly conserved serine/threonine protein kinase in alpha-herpesviruses. In other alpha-herpesviruses, such as pseudorabies virus (PRV), US3 phosphorylates the N6-methyladenosine (m6A) methyltransferase Wilms tumor 1-associated protein (WTAP), inhibiting m6A modification. However, the role and mechanism of US3-mediated WTAP phosphorylation during MDV infection remain undefined. Our study revealed that MDV infection in vitro does not alter WTAP expression, while significant changes in WTAP expression occur during the MDV life cycle in vivo. We demonstrated that MDV-encoded US3 interacts with and co-localizes with WTAP in the nucleus. Further analysis showed that US3 binds to WTAP's C-terminal domain and phosphorylates WTAP at S273, S305, S314, and S375. Notably, the interaction between US3 and WTAP does not affect WTAP stability but inhibits transcriptomic m6A modification and cellular protein translation. Therefore, these findings enhance our understanding of the molecular mechanisms underlying MDV infection.

Optimizing encephalomyocarditis virus VP1 protein assembly on pseudorabies virus envelope via US9 protein anchoring

ABSTRACT Live herpesvirus-vectored vaccines are critical in veterinary medicine, but they can sometimes offer insufficient protection due to suboptimal antigen expression or localization. Encephalomyocarditis virus (EMCV) is a significant zoonotic threat, with VP1 protein as a key immunogen on its capsid. To enhance immunogenicity, we explored the use of recombinant pseudorabies virus (rPRV) as a vaccine vector against EMCV. In silico analysis indicated that fusing VP1 with US9 enhances the formation of a type II transmembrane heterodimer. We constructed six rPRV groups expressing different VP1 variants and found that VP1 fused with US9’s C-terminal (US9-VP1) enhances VP1’s membrane localization and its incorporation into the PRV envelope, unlike wild-type VP1. Immunogold electron microscopy illustrated that rPRV with deleted US8 and US9, supplemented with US8 regulatory sequence (rΔ89-U9VP1), improved VP1 incorporation into the viral envelope. Post-immunization, only rΔ89-U9VP1 provided 100% protection against EMCV in mice and induced high levels of virus-neutralizing antibodies in piglets. Additionally, rPRV expressing VP1 stimulated robust T-cell responses, as demonstrated by flow cytometry and ELISpot assays. This study introduces rPRV as a potential EMCV vaccine, demonstrating that the selection of the US9 C-terminal domain and US8 regulatory sequence significantly enhances the presentation of heterologous antigens, improving vaccine efficacy.

Deletion of gE in Herpes Simplex Virus 1 Leads to Increased Extracellular Virus Production and Augmented Interferon Alpha Production by Peripheral Blood Mononuclear Cells.

Herpes simplex virus (HSV) in humans and pseudorabies virus (PRV) in pigs are both alphaherpesviruses. Plasmacytoid dendritic cells (pDCs) make part of the peripheral blood mononuclear cells (PBMCs) and are specialized in producing large amounts of antiviral type I interferon (IFN-I). IFN-I production by PBMCs in response to both HSV-1 and PRV can be virtually exclusively attributed to pDCs. Recently, we discovered that cells infected with gEnull PRV trigger increased production of IFNalpha by porcine PBMCs/pDCs compared with cells infected with wild-type (WT) PRV. This increased IFNalpha response correlates with increased extracellular virus production triggered by gEnull PRV compared with WT PRV. The gE protein and some of its currently described functions are conserved in different alphaherpesviruses, including PRV and HSV-1. In the current study, we report that cells infected with gEnull HSV-1 trigger increased IFNalpha production by human PBMCs and increased extracellular virus production compared with WT HSV-1. Hence, these recently described functions of PRV gE are conserved in HSV-1 gE. Since the increased extracellular virus production and IFNalpha response have also been reported for successful (gEnull) PRV vaccines, the current findings may have important consequences for the rational design of HSV vaccines.

Pseudorabies virus as a zoonosis: scientific and public health implications.

Pseudorabies virus (PRV) is a herpes virus, also known as Aujeszky's disease virus (ADV), which can cause a highly infectious disease pseudorabies (PR) in a variety of mammals. In the past, it has been debated whether PRV can infect humans, but more and more cases of PRV infection have been reported since 2017. The illness has claimed many victims and left survivors with serious sequelae. This indicates that humans may ignore the zoonotic ability of PRV. This review aims to summarize the pathology and pathogenesis of PRV and speculate on how it infects humans. This paper provides a comprehensive overview of the progression of PRV, including its virology characteristics, genomic organization, and genetic evolution. It also synthesises the existing literature on PRV infection in humans, and analyses the factors contributing to PRV zoonosis. Finally, the pathogenesis of PRV-infected pigs and other mammals was summarized, and the pathogenesis of PRV-infected humans was speculated.

Nucleotide-binding oligomerization domain 1 (NOD1) regulates microglial activation in pseudorabies virus infection

The primary cause of viral encephalitis (VE) is invasion of the central nervous system (CNS) by the virus, which leads to neuroinflammation and poses a significant threat to global public health. Microglia, as CNS-resident macrophages, play a crucial role in neuroinflammation and are often identified as the preferred target for the prevention or treatment of VE. In this study, we used pseudorabies virus (PRV)-induced VE in mice and pigs as a model to investigate the regulation of microglial responses during viral encephalitis and explored the mechanism of microglial activation. Cellular experiments revealed that microglial activation was accompanied by cell migration, characteristic morphological changes, phagocytosis, inflammatory cytokine production, and antigen presentation. Transcriptome analysis revealed that genes related to inflammation in PRV-infected BV2 cells were significantly enriched. The expression of the NOD1 gene in BV2 cells was significantly increased during PRV infection, after which NOD1 in BV2 cells was silenced by siRNA and overexpressed via a plasmid. NOD1 was found to be involved in the secretion of cytokines in BV2 cells by regulating the MAPK/NF-κB signalling pathway. Mouse and pig experiments have shown that NOD1 is involved in the secretion of cytokines by microglia by regulating the MAPK/NF-κB signalling pathway during PRV infection.

A previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p/KEAP1 axis.

Circular RNAs (circRNAs) exert diverse biological functions in different processes. However, the role of circRNAs during virus infection is mostly unknown. Herein, we explored the characteristics of host circRNAs using alphaherpesvirus pseudorabies virus (PRV) as a model. PRV infection upregulated the expression of circRNA circ29164, which does not encode a protein. RNA pulldown assays identified that circ29164 interacts with the microRNA ssc-miRNA-24-3p. Further analysis indicated that ssc-miR-24-3p targets the mRNA encoding kelch-like ECH-associated protein 1 (KEAP1), and circ29164 competitively binds to ssc-miR-24-3p to prevent it binding to Keap1. Apoptosis detection demonstrated that circ29164 or Keap1 overexpression, but not knockdown, induced caspase 3 activity and the release of cytochrome C from mitochondria, and inhibited PRV replication. Taken together, these data identified a previously undiscovered circRNA, circ29164, which inhibits PRV replication by competitively binding to ssc-24-3p to maintain KEAP1 levels.

Identification of NECTIN1 as a novel restriction factor for flavivirus infection.

NECTIN1, also known as CD111 or PVRL1, has been recognized as the primary receptor for several alpha herpesviruses, including herpes simplex virus (HSV), pseudorabies virus (PRV), and bovine herpesvirus 1 (BHV-1). However, our study revealed a novel role for NECTIN1 in the virus life cycle by influencing BVDV infection. Contrary to its role as a receptor for alpha herpesviruses, NECTIN1 acts as a restriction factor for BVDV by inhibiting viral attachment via competition with CD46 for binding to the domain DD of BVDV E2. We further revealed that the replication of members of the Flaviviridae family was inhibited by NECTIN1, while the replication of other RNA viruses did not significantly differ. Our results demonstrate that NECTIN1 is a novel factor restricting Flaviviridae family virus replication and highlight the complexity of virus-host interactions and the multifaceted nature of host factors involved in viral infection.

A Quadruplex RT-qPCR for the Detection of African Swine Fever Virus, Classical Swine Fever Virus, Porcine Reproductive and Respiratory Syndrome Virus, and Porcine Pseudorabies Virus.

African swine fever virus (ASFV), classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine pseudorabies virus (PRV) induce similar clinical signs in infected pigs, including hyperthermia, anorexia, hemorrhage, respiratory distress, neurological symptoms, and/or abortions in pregnant sows. The differential diagnosis of these diseases relies on laboratory examinations. In this study, a quadruplex RT-qPCR was established using four pairs of specific primers and probes aimed at the B646L (p72) gene of ASFV, the 5' untranslated region (5'UTR) of CSFV, the ORF6 gene of PRRSV, and the gB gene of PRV for the detection and differentiation of ASFV, CSFV, PRRSV, and PRV. The assay exhibited great sensitivity with limits of detection (LODs) of 134.585, 139.831, 147.076, and 142.331 copies/reaction for ASFV, CSFV, PRRSV, and PRV, respectively. The assay exclusively identified ASFV, CSFV, PRRSV, and PRV, yielding negative results for the other control swine viruses used in this study. The intra-assay and inter-assay coefficients of variation (CVs) were not higher than 1.12%, indicating good reproducibility of the assay. The quadruplex RT-qPCR assay was used to analyze 3116 clinical tissue samples from pigs in Guangxi province, China, from April 2023 to September 2024. ASFV, CSFV, PRRSV, and PRV had positivity rates of 10.84% (338/3116), 0.80% (25/3116), 14.92% (465/3116), and 1.38% (43/3116), respectively, demonstrating a coincidence rate of ≥99.45% with the previously described RT-qPCR assays, which were also used to test these same samples. The established assay was rapid, sensitive, and accurate in detecting and differentiating ASFV, CSFV, PRRSV, and PRV.

Evasion of the Antiviral Innate Immunity by PRV.

Pseudorabies virus (PRV) establishes persistent latent infections by effectively evading the host's antiviral innate immune response. PRV has developed sophisticated strategies to bypass immune surveillance through coevolution with its host. Currently, no effective vaccine exists to prevent or treat infections caused by emerging PRV variants, and the interactions between PRV and the host's innate immune defenses remain incompletely understood. Nevertheless, ongoing research is uncovering insights that may lead to novel treatments and preventive approaches for herpesvirus-related diseases. This review summarizes recent advances in understanding how PRV disrupts key adaptors in immune signaling pathways to evade antiviral immunity. Additionally, we explored the intrinsic cellular defenses that play crucial roles in combating viral invasion. A deeper understanding of the immune evasion strategies of PRV could inform the development of new therapeutic targets and vaccines.

Tethered release of the pseudorabies virus deubiquitinase from the capsid promotes enzymatic activity.

Neuroinvasive alphaherpesviruses, such as herpes simplex virus and pseudorabies virus, cause a broad range of diseases in humans and other animals. Novel strategies to interfere with the virion structural rearrangements required for infectivity could prove valuable to treat infections, yet critical aspects of the virion architecture and its metastability remain poorly defined. In this study, we document that the pUL36 tegument protein exhibits conditional capsid binding in its N-terminal deubiquitinase domain that regulates enzymatic activity during infection.

Chemical and Heat Treatment for Viral Inactivation in Porcine-Derived Gelatin

BackgroundIt is mandatory to demonstrate the removal or inactivation of potential viral contaminants in the manufacturing processes of pharmaceuticals derived from biomaterials. Porcine-derived gelatin is used in various medical fields, including regenerative medicine, tissue engineering, and medical devices. However, the steps of virus inactivation in the gelatin manufacturing process are poorly defined. In this study we evaluated virus inactivation in two steps of the gelatin manufacturing process.MethodsPig skin (4.5 g), including solid pieces as intermediate products, was spiked with model viruses, including CPV (canine parvovirus), BAV (bovine adenovirus), BPIV3 (bovine parainfluenza type 3), PRV (pseudorabies virus), BReoV3 (bovine reovirus type 3), and PPV (porcine parvovirus), and underwent chemical treatment with alkaline ethanol or heat treatment at 62 °C followed by inoculation in relevant cell cultures. Viral titers in the samples were calculated based on the Behrens-Kärber method.ResultsModel viruses were inactivated at different rates; however, effective inactivation of all model viruses was demonstrated by an LRV (log reduction value) over 4 by both chemical and heat treatment, and chemical treatment demonstrated rapid inactivation compared to heat treatment.ConclusionThe chemical and heat treatment steps exhibited meaningful viral inactivation capacity. They are integrated parts in the extraction and manufacturing process of porcine-derived gelatin, ensuring virus safety for use in medical applications.