Pseudorabies Virus Infection Research Articles

HSP27 Attenuates cGAS-Mediated IFN-β Signaling through Ubiquitination of cGAS and Promotes PRV Infection.

Pseudorabies (PR) is a domestic and wild animal infectious disease caused by the pseudorabies virus (PRV) and is one of the major infectious diseases that endanger the global swine industry. Studies have reported that PRV may achieve cross-species transmission from pigs to humans in recent years. Therefore, in-depth exploration of the relationship between PRV and host proteins is of great significance for elucidating the pathogenic mechanism of PRV and anti-PRV infection. Here, we report that heat shock protein 27 (HSP27) ubiquitinates and degrades cyclic GMP-AMP synthase (cGAS) and attenuates cGAS-mediated antiviral responses, thereby promoting PRV infection. Overexpression of HSP27 promoted PRV proliferation in vitro, while knockdown of HSP27 inhibited PRV infection. Importantly, we found that HSP27 inhibited PRV infection or poly(dA:dT)-activated IFN-β expression. Further studies found that HSP27 may inhibit cGAS-STING-mediated IFN-β expression through targeting cGAS. In addition, we found that HSP27 can suppress the expression of endogenous cGAS in different cells at both gene transcription and protein expression levels, and that HSP27 interacts with and ubiquitinates cGAS. In conclusion, we reveal for the first time that HSP27 is a novel negative regulator of the cGAS-STING signaling pathway induced by PRV infection or poly(dA:dT) activation and demonstrate that HSP27 plays a crucial role in PRV infection.

Glycyrrhiza Polysaccharide Inhibits Pseudorabies Virus Infection by Interfering with Virus Attachment and Internalization.

Pseudorabies virus (PRV) is one of the most important pathogens causing serious diseases and leads to huge economic losses in the global swine industry. With the continuous emergence of PRV variants and the increasing number of cases of human infection, there is an urgent need to develop antiviral drugs. In this study, we discover that Glycyrrhiza polysaccharide (GCP) has anti-PRV infection activity in vitro, and 600 μg/mL GCP can completely block viral infection. The addition of GCP simultaneously with or after PRV infection had a significant inhibitory effect on PRV. Addition of GCP at different times of the virus life cycle mainly led to the inhibition of the attachment and internalization of PRV but does not affect viral replication and release. Our findings suggest that GCP has potential as a drug against PRV infection.

Progress of Research into Novel Drugs and Potential Drug Targets against Porcine Pseudorabies Virus.

Pseudorabies virus (PRV) is the causative agent of pseudorabies (PR), infecting most mammals and some birds. It has been prevalent around the world and caused huge economic losses to the swine industry since its discovery. At present, the prevention of PRV is mainly through vaccination; there are few specific antivirals against PRV, but it is possible to treat PRV infection effectively with drugs. In recent years, some drugs have been reported to treat PR; however, the variety of anti-pseudorabies drugs is limited, and the underlying mechanism of the antiviral effect of some drugs is unclear. Therefore, it is necessary to explore new drug targets for PRV and develop economic and efficient drug resources for prevention and control of PRV. This review will focus on the research progress in drugs and drug targets against PRV in recent years, and discuss the future research prospects of anti-PRV drugs.

DDX56 inhibits PRV replication through regulation of IFN-β signaling pathway by targeting cGAS.

Pseudorabies virus (PRV) is an agent of Aujeszky's disease, and causes great economic losses to pig farming. Re-outburst of pseudorabies implies that new control measures are urgently needed. We show here that DDX56 possesses the ability to inhibit PRV replication in vitro, which may be an important factor for PRV infection. Overexpression of DDX56 inhibited PRV genomic DNA transcription and lower titers of PRV infection in PK15 cells, whereas down-regulation of the DDX56 expression had a promotion role on virus replication. Further study demonstrated that DDX56 exerted its proliferation-inhibitory effects of PRV through up-regulating cGAS-STING-induced IFN-β expression. Moreover, we found that DDX56 could promote cGAS expression and direct interaction also existed between DDX56 and cGAS. Based on this, DDX56-regulated IFN-β pathway may be targeted at cGAS. To verify this, down-regulated cGAS expression in DDX56 over-expression cells was performed. Results indicated that knockdown of cGAS expression could abrogate the inhibition role of DDX56 on PRV proliferation and weaken the effect of DDX56 on IFN-β expression. In addition, DDX56 played a promotion role in IRF3 phosphorylation and nucleus translocation. Altogether, our results highlight DDX56's antiviral role in PRV infection, and our findings contribute to a better understanding of host factors controlling PRV replication.

Risk Factors and Spatial-Temporal Analysis of Porcine Reproductive and Respiratory Syndrome Seroprevalence in China Before and After African Swine Fever Outbreak.

Porcine reproductive and respiratory syndrome (PRRS) is an infectious viral disease that causes great harm to the pig industry. PRRS virus (PRRSV), the causative agent of PRRS, is characterized by severe reproductive failure and respiratory confusion. This study performed a cross-sectional investigation of PRRSV seroprevalence and collected 14,134 serum samples in pig farms without PRRSV vaccination from 12 provinces and two cities in China from 2017 to 2021 to detect PRRSV antibodies by enzyme-linked immunosorbent assay (ELISA). The apparent and true PRRSV antibody prevalence was estimated and compared based on the Clopper-Pearson method and Pearson chi-square test, respectively. Risk factors associated with the PRRSV serological status of pig farms were analyzed through univariate and multivariable logistic regression analysis. An automatic autoregressive integrated moving average (ARIMA) model procedure was used for time-series analysis for PRRSV seroprevalence. Spatial clusters of high PRRSV seroprevalence were detected by SaTScan software. The total true PRRSV seroprevalence of the animal level was 62.56% (95% confidence interval [CI]: 61.74–63.37%). Additionally, 286 out of 316 pig farms were positive for PRRSV antibodies at the herd level. Pig farms without pseudorabies virus (PRV) infection were 5.413 (95% CI: 1.977–17.435) times more likely to be PRRSV antibody positive than those with PRV. Identically, the possibility of pig farms being PRRSV antibody positive before an African swine fever (ASF) outbreak was 3.104 (95% CI: 1.122–10.326) times more than after ASF. The odd ratio values of medium and large pig farms with PRRSV infection are 3.076 (95% CI: 1.005–9.498) and 6.098 (95% CI: 1.814–21.290). A fluctuant decline pattern for PRRSV prevalence was observed in the temporal analysis. Three significant clusters of high PRRSV seroprevalence were first detected in China, covering a time frame from January 2018 to September 2018, which reveals high PRRSV prevalence before the outbreak of ASF. These findings show the epidemic situation and spatial-temporal distribution of PRRSV infection in China in recent years and could help develop reasonable measures to prevent PRRSV infection.

Correction for Romero et al., "Pseudorabies Virus Infection Results in a Broad Inhibition of Host Gene Transcription".

Volume 96, no. 13, e00714-22, 2022, https://doi.org/10.1128/jvi.00714-22. Page 12: During assembly of Fig. 5, inadvertently, the same set of graphs (corresponding to panel E) was used mistakenly for both panels C and E. In addition, the figure legend incorrectly indicated that the graphs in panel C and E were derived from three independent repeats, but they were derived from two independent repeats. The corrected graphs now show the average and the individual data points from the two independent repeats to indicate these repeats more clearly. These corrections do not affect any of the conclusions of the paper.

Pseudorabies Virus: From Pathogenesis to Prevention Strategies.

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.

A poly(dimethylsiloxane)-based solid-phase microchip platform for dual detection of Pseudorabies virus gD and gE antibodies.

Pseudorabies caused by pseudorabies virus (PRV) infection is still a major disease affecting the pig industry; its eradication depends on effective vaccination and antibody (Ab) detection. For a more rapid and accurate PRV detection method that is suitable for clinical application, here, we established a poly(dimethylsiloxane)-based (efficient removal of non-specific binding) solid-phase protein chip platform (blocking ELISA) for dual detection of PRV gD and gE Abs. The purified gD and gE proteins expressed in baculovirus were coated into the highly hydrophobic nanomembrane by an automatic spotter, and the gray values measured by a scanner were used for the S/N (sample/negative) value calculation (gD and gE Abs standard, positive: S/N value ≤0.6; negative: S/N value >0.7; suspicious: 0.6 < S/N ≤ 0.7). The method showed an equal sensitivity in the gD Ab test of immunized pig serum samples compared to the neutralization test and higher sensitivity in the gE Ab test compared to the commercial gE Ab detection kit. In the clinical evaluation, we found an agreement of 100% (122/122) in the gD Ab detection compared to the neutralization test and an agreement of 97.5% (119/122) in the gE Ab detection compared to the commercial PRV gE Ab detection kit. In summary, the protein chip platform for dual detection of PRV gD and gE Abs showed high sensitivity and specificity, which is suitable for PRV immune efficacy evaluation and epidemic monitoring.

Specific inhibition of the interaction between pseudorabies virus DNA polymerase subunits UL30 and UL42 by a synthetic peptide

Pseudorabies virus (PRV) is a ubiquitous and economically important swine alphaherpesvirus that causes devastating swine diseases worldwide. PRV-encoded DNA-dependent DNA polymerase, comprised of the catalytic subunit UL30 and the accessory subunit UL42, is essential for viral replication. PRV UL30 and UL42 act as a heterodimer with UL30 harboring inherent DNA polymerase activity and UL42 conferring processivity on the DNA polymerase holoenzyme. The formation of PRV UL30/UL42 heterodimer holoenzyme through protein-protein interactions is indispensable for viral replication. In work described here, we defined the key domains that mediate PRV UL30/UL42 interaction, and found that the 41 carboxy-terminal amino acids region of PRV UL30 is critical for its interaction with UL42. Intriguingly, a synthetic peptide corresponding to these 41 carboxy-terminal amino acid residues efficiently disrupted PRV UL30/UL42 interaction through competitively binding to UL42. These findings suggest that the peptides from the PRV DNA polymerase UL30/UL42 subunit interface may represent potential targets for designing a novel intervention strategy against PRV infection. This work further strengthens the concept that the herpesvirus DNA polymerase catalytic subunits utilize their extreme carboxy-terminal domains as a conserved mechanism to associate with their cognate accessory subunits, providing us the opportunity of designing novel antiviral agents against herpesvirus infection through disruption of the herpesvirus DNA polymerase subunit interactions.

The Cholesterol Transport Inhibitor U18666A Interferes with Pseudorabies Virus Infection.

Many viruses require the maintenance of lysosomal cholesterol homeostasis for a successful infection; however, the role of lysosomal cholesterol homeostasis in the alphaherpesvirus life cycle is not clear. Here we show that the lysosomal cholesterol transport inhibitor U18666A interferes with the replication of pseudorabies virus (PRV), a member of the alphaherpesvirus subfamily. The treatment with U18666A caused a significant reduction in the production of infectious virus particles. The U18666A treatment was shown to suppress the release of PRV particles. Pretreating PRV virions with U18666A did not affect virus production, whereas pretreating target cells with U18666A led to a substantial reduction in virus yield. Our previous study showed that two cyclodextrin derivatives, 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 2-hydroxypropyl-γ-cyclodextrin (HPγCD), can rescue the cholesterol accumulation defect in primary fibroblasts derived from a Niemann–Pick disease type C (NPC) patient. Here, we demonstrate that treatment with HPβCD or HPγCD not only rescues the U18666A-induced cholesterol accumulation but also rescues the U18666A-induced inhibition of PRV production. Collectively, our data suggest that U18666A interferes with PRV infection via altering cellular functions that are critical for the viral life cycle and may include lysosomal cholesterol homeostasis.

The canonical Wnt/β-catenin signaling pathway facilitates pseudorabies virus proliferation and enhances virus-induced autophagy

Pseudorabies virus (PRV) is a swine herpesvirus with a broad host range that causes significant economic losses worldwide. The Wnt/β-catenin signaling pathway is reportedly involved in multiple viruses' proliferation. In this study, we demonstrated that PRV infection significantly activated the Wnt/β-catenin signaling and promoted the nuclear translocation of β-catenin. Applying specific chemical inhibitors (FH535 and iCRT14) caused a remarkable decrease in PRV titers in various cell lines. Knockdown of β-catenin by siRNA also reduced the proliferation of PRV. On the contrary, treatment with lithium chloride (LiCl), an inhibitor of GSK3β, stimulated the Wnt/β-catenin signaling pathway and enhanced the PRV proliferation. Similarly, overexpression of β-catenin promoted PRV proliferation and reversed the antiviral effect of FH535. Moreover, LiCl promoted PRV-induced autophagy, whereas FH535 and iCRT14 showed converse effects. These findings suggest that PRV infection stimulates the canonical Wnt/β-catenin signaling pathway, facilitating PRV proliferation and regulating virus-induced autophagy. These data also provide potential targets for developing antiviral agents against PRV.

The Epidemiology and Variation in Pseudorabies Virus: A Continuing Challenge to Pigs and Humans.

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.

Antiviral effect of an extract from Kaempferia galanga L. rhizome in mice infected with pseudorabies virus

Pseudorabies virus (PrV) is one of the most important herpesviruses which can cause severe diseases in many mammals and some avian species. In recent years, repeated outbreaks of pseudorabies worldwide indicated an urgent need for new control measures. The results described in this study demonstrated that an extract prepared from the rhizome of Kaempferia galanga L (Kge), which consisted of flavonoids (2.82%), saccharides (61.37%), phenols (1.22%) and saponins (3.10%), possessed a potent anti-PrV activity. In PK-15 cells, Kge treatment inhibited PrV-induced cell death by more than 90% at a dose of 200 μg/mL. The 50% inhibitory concentration (IC50) was 55.85 μg/mL. In the PrV-infected mice treated with Kge, the survival rate was up to 60% at day 6 post-infection, while the infected mice without Kge treatment all died. The virus titers in the brains of the Kge-treated infected mice were significantly reduced. Kge treatment also alleviated the severity of the PrV-induced lesions in the heart, liver, spleen, lung and kidney. Kge exhibited immune-regulating activity through the regulation of cytokines (IFN-α, IFN-β, IL-4, IL-6 and TNF-α) in the serum of PrV-infected mice, suggesting that one possible mechanism of anti-PrV activity was through the regulation of immune function. These results suggested that Kge could be a promising drug candidate for treating PrV infections.

The Role of Latency-Associated Transcripts in the Latent Infection of Pseudorabies Virus.

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.

Epidemiological Investigation of Porcine Pseudorabies Virus in Hebei Province, China, 2017-2018.

Pseudorabies (PR) is a serious disease affecting the pig industry in China, and it is very important to understand the epidemiology of pseudorabies virus (PRV). In the present study, 693 clinical samples were collected from Bartha-K61 vaccinated pigs with symptoms of suspected PRV infection between January 2017 and December 2018. All cases were referred for full clinical autopsy with detailed examination of histopathological examination, virus isolation and genetic evolution analysis of the PRV glycoprotein E (gE) gene. In addition, PRV gE antibodies in 3,449 serum samples were detected by the enzyme-linked immunosorbent assay (ELISA). The clinical data revealed that abortion and stillbirth are the most frequent appearances in pregnant sows of those cases. Histopathological examination exhibited a variety of pathological lesions, such as lobar pneumonia, hepatitis, lymphadenitis, nephritis, and typical nonsuppurative encephalitis. A total of 248 cases tested positive for the PRV gE gene. 11 PRV variants were isolated and confirmed by gE gene sequencing and phylogenetic analysis. These strains had 97.1%-100.0% nucleotide homology with the PRV reference strains. Notably, the isolated strains were highly homologous and clustered in the same branch as HSD-1/2019, which caused human acute encephalitis. Serological tests showed that the positive rate of PRV gE antibody in the 3449 serum samples collected from the Hebei Province was 46.27%. In conclusion, PRV variant strains Are high prevalence in the Hebei Province, which not only causes huge economic losses to the breeding industry but also potentially poses a threat to public health.

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

Pseudorabies virus (PRV) is a porcine alphaherpesvirus that belongs to the Herpesviridae family. We showed earlier that infection of porcine epithelial cells with PRV triggers activation of the nuclear factor κB (NF-κB) pathway, a pivotal signaling axis in the early immune response. However, PRV-induced NF-κB activation does not lead to NF-κB-dependent gene expression. Here, using electrophoretic mobility shift assays (EMSAs), we show that PRV does not disrupt the ability of NF-κB to interact with its κB target sites. Assessing basal cellular transcriptional activity in PRV-infected cells by quantitation of prespliced transcripts of constitutively expressed genes uncovered a broad suppression of cellular transcription by PRV, which also affects the inducible expression of NF-κB target genes. Host cell transcription inhibition was rescued when viral genome replication was blocked using phosphonoacetic acid (PAA). Remarkably, we found that host gene expression shutoff in PRV-infected cells correlated with a substantial retention of the NF-κB subunit p65, the TATA box binding protein, and RNA polymerase II-essential factors required for (NF-κB-dependent) gene transcription-in expanding PRV replication centers in the nucleus and thereby away from the host chromatin. This study reveals a potent mechanism used by the alphaherpesvirus PRV to steer the protein production capacity of infected cells to viral proteins by preventing expression of host genes, including inducible genes involved in mounting antiviral responses. IMPORTANCE Herpesviruses are highly successful pathogens that cause lifelong persistent infections of their host. Modulation of the intracellular environment of infected cells is imperative for the success of virus infections. We reported earlier that a DNA damage response in epithelial cells infected with the alphaherpesvirus pseudorabies virus (PRV) results in activation of the hallmark proinflammatory NF-κB signaling axis but, remarkably, that this activation does not lead to NF-κB-induced (proinflammatory) gene expression. Here, we report that PRV-mediated inhibition of host gene expression stretches beyond NF-κB-dependent gene expression and in fact reflects a broad inhibition of host gene transcription, which correlates with a substantial recruitment of essential host transcription factors in viral replication compartments in the nucleus, away from the host chromatin. These data uncover a potent alphaherpesvirus mechanism to interfere with production of host proteins, including proteins involved in antiviral responses.

Characterization of B cell receptor H-CDR3 repertoire of spleen in PRV-infected mice

Pseudorabies virus (PRV), also known as suid Alphaherpesvirus 1 (SuHV-1), which is one of the most devastating infectious pathogen of swine industry worldwide. Vaccination is the safest and most effective PRV prevention and control strategy. B cell receptor (BCR) is membrane-bound immunoglobulin located on the surface of B cells capable of specifically binding foreign antigens, which is one of the most important molecules regulating the proliferation and function of B cells. Here, to assess the molecular diversity of BCR H-CDR3 repertoire after different PRV strains infection, we detected the IGHV, IGHD, IGHJ genes usage and CDR3 sequence changes of mice spleen with PRV vaccine strain (Bartha-K61), variant strain (XJ) and mock infection by high-throughput sequencing. We found that PRV-infected groups shared partial BCR sequences, which are most likely to be PRV-specific BCR candidates. However, there were still differences in the IGHV genes usage as well as the combined usage of IGHV and IGHJ genes between the Bartha-K61 strain and XJ strain infection groups. In addition, the CDR3 sequences exhibited large differences in the types and lengths in PRV infection groups. Our study contributes to a better understanding of the host adaptive immune response to PRV infection and provides a theoretical basis for further research on novel and efficient PRV vaccines in the future.

Phospho-proteomics identifies a critical role of ATF2 in pseudorabies virus replication.

Pseudorabies virus (PRV), an etiological agent of pseudorabies in livestock, has negatively affected the porcine industry all over the world. Epithelial cells are reported as the first site of PRV infection. However, the role of host proteins and its related signaling pathways in PRV replication is largely unclear. In this study, we performed a quantitative phosphoproteomics screening on PRV-infected porcine kidney (PK-15) epithelial cells. Totally 5723 phosphopeptides, corresponding to 2180 proteins, were obtained, and the phosphorylated states of 810 proteins were significantly different in PRV-infected cells compared with mock-infected cells (P ​< ​0.05). GO and KEGG analysis revealed that these differentially expressed phosphorylated proteins were predominantly related to RNA transport and MAPK signaling pathways. Further functional studies of NF-κB, transcription activator factor-2 (ATF2), MAX and SOS genes in MAPK signaling pathway were analyzed using RNA interference (RNAi) knockdown. It showed that only ATF2-knockdown reduces both PRV titer and viral genome copy number. JNK pathway inhibition and CRISPR/Cas9 gene knockout showed that ATF2 was required for the effective replication of PRV, especially during the biogenesis of viral genome DNA. Subsequently, by overexpression of the ATF2 gene and point mutation of the amino acid positions 69/71 of ATF2, it was further demonstrated that the phosphorylation of ATF2 promoted PRV replication. These findings suggest that ATF2 may provide potential therapeutic target for inhibiting PRV infection.

Teaching NeuroImage: Human Encephalitis Caused by Pseudorabies Virus Infection.

A 51-year-old woman presented with fever and loss of consciousness for 4 days. Images showed symmetrical lesions in bilateral cortex, limbic system, and basal ganglia (Figure). CSF analysis suggested viral infection. Next-generation sequencing identified 349 unique sequence reads for pseudorabies virus (PRV). She was diagnosed with PRV encephalitis. Epidemiologic survey revealed she was a pork dealer. PRV, also called Suid herpesvirus-1, primarily infects swine. It is reported that PRV can cause human infection through infected swine or pork.1,2 This case suggests unexplained severe encephalitis with similar MRI, and a history of relevant exposure should consider the possibility of PRV infection.

Metabolomics Analysis of PK-15 Cells with Pseudorabies Virus Infection Based on UHPLC-QE-MS.

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.