Explore the vast range of titles available.

Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) is one of the most economically important diseases, that has significantly impacted the global pork industry for over three decades, since it was first recognized in the United States in the late 1980s. Attributed to the PRRSV extensive genetic and antigenic variation and rapid mutability and evolution, nearly worldwide epidemics have been sustained by a set of emerging and re-emerging virus strains. Since the first modified live virus (MLV) vaccine was commercially available, it has been widely used for more than 20 years, for preventing and controlling PRRS. On the one hand, MLV can induce a protective immune response against homologous viruses by lightening the clinical signs of pigs and reducing the virus transmission in the affected herd, as well as helping to cost-effectively increase the production performance on pig farms affected by heterologous viruses. On the other hand, MLV can still replicate in the host, inducing viremia and virus shedding, and it fails to confer sterilizing immunity against PRRSV infection, that may accelerate viral mutation or recombination to adapt the host and to escape from the immune response, raising the risk of reversion to virulence. The unsatisfied heterologous cross-protection and safety issue of MLV are two debatable characterizations, which raise the concerns that whether it is necessary or valuable to use this leaky vaccine to protect the field viruses with a high probability of being heterologous. To provide better insights into the immune protection and safety related to MLV, recent advances and opinions on PRRSV attenuation, protection efficacy, immunosuppression, recombination, and reversion to virulence are reviewed here, hoping to give a more comprehensive recognition on MLV and to motivate scientific inspiration on novel strategies and approaches of developing the next generation of PRRS vaccine.

We study the Riemann problem and flux-approximation limits of solutions to the relativistic Euler equations with the state equation for modified Chaplygin gas. The limits of Riemann solutions for the relativistic modified Chaplygin gas equations and the corresponding flux-approximation system are discussed when the pressure term and flux-perturbation parameters tend to zero. It is rigorously proved that, as the pressure and flux approximations vanish respectively, any two-shock-wave Riemann solution tends to a delta-shock solution to the pressureless relativistic Euler equations, and the intermediate density between them tends to a weighted δ-measure that forms a delta shock wave. Correspondingly, any two-rarefaction-wave solution becomes two contact discontinuities connecting the constant states and vacuum states, which form a vacuum solution.

Swine infectious diseases, often caused by multiple co-infecting agents, pose severe global threats to pig health and industry economics. Conventional single-plex testing assays, whether relying on pathogen antigens or nucleic acids, exhibit limited efficacy in the face of co-infection events. The modern nucleic acid-based multiplex testing (NAMT) methods demonstrate substantial strengths in the simultaneous detection of multiple pathogens involving co-infections owing to their remarkable sensitivity, exceptional specificity, high-throughput, and short turnaround time. The development, commercialization, and application of NAMT assays in swine infectious disease surveillance would be advantageous for early detection and control of pathogens at the onset of an epidemic, prior to community transmission. Such approaches not only contribute to saving the lives of pigs but also aid pig farmers in mitigating or preventing substantial economic losses resulting from infectious disease outbreaks, thereby alleviating unwanted pressure on animal and human health systems. The current literature review provides an overview of some modern NAMT methods, such as multiplex quantitative real-time PCR, multiplex digital PCR, microarrays, microfluidics, next-generation sequencing, and their applications in the diagnosis of swine infectious diseases. Furthermore, the strengths and weaknesses of these methods were discussed, as well as their future development and application trends in swine disease diagnosis.

This paper is concerned with the four-wave Riemann problem for a two-dimensional hyperbolic system of nonlinear conservation laws derived from a quasi-linear wave equation. The self-similar form of this system is of mixed type. The four-wave Riemann problem in the self-similar plane consists of interactions of four planar elementary waves (exterior waves), which contain rarefaction waves, shocks and contact discontinuities. The Riemann problem is classified into sixteen genuinely different nontrivial cases. The structures of solutions for four rarefaction waves, four shocks and two nonadjacent rarefaction waves plus two nonadjacent shocks are constructed completely. For the rest cases, the solutions are roughly analyzed. For each case, the corresponding numerical solutions are illustrated via contour plots. Comparing with the compressible Euler equations and related models, one of the highlights for this paper is that the interactions of two rarefaction waves, two shocks, as well as a rarefaction wave and a shock in hyperbolic domains are clarified.

Porcine deltacoronavirus (PDCoV) is an emerging enteropathogen which mainly causes diarrhea, dehydration and death in nursing piglets, threatening the global swine industry. Moreover, it can infect multiple animal species and humans. Hence, reliable diagnostic assays are needed to better control this zoonotic pathogen. Here, a blocking ELISA was developed using a recombinant nucleocapsid (N) protein as the coating antigen paired with an N-specific monoclonal antibody (mAb) as the detection antibody. The percent inhibition (PI) of the ELISA was determined using 384 swine serum samples, with an indirect immunofluorescence assay (IFA) as the reference method. Through receiver operating characteristic analysis in conjunction with Youden’s index, the optimal PI cut-off value was determined to be 51.65%, which corresponded to a diagnostic sensitivity of 98.79% and a diagnostic specificity of 100%. Of the 330 serum samples tested positive via IFA, 326 and 4 were tested positive and negative via the ELISA, respectively, while the 54 serum samples tested negative via IFA were all negative via the ELISA. The overall coincidence rate between the two assays was 98.96% (380/384). The ELISA exhibited good repeatability and did not cross-react with antisera against other swine pathogens. Overall, this is the first report on developing a blocking ELISA for PDCoV serodiagnosis.

African swine fever virus (ASFV) has inflicted severe devastation on the global pig industry, yet a globally approved vaccine remains unavailable. Given that cellular immunity is critical for ASFV prevention, the development of vaccines based on T-cell epitopes emerges as a promising strategy to control this virus. This review synthesizes the recent advancements and challenges in the research on ASFV T-cell epitopes, while offering insights into the potential impact of novel T-cell epitope-based vaccines. Notably, only a limited number of ASFV T-cell epitopes have been experimentally identified to date, covering fewer than 20 ASFV proteins. This bottleneck is attributed to challenges such as high swine leukocyte antigen (SLA) polymorphism, suboptimal accuracy of predicting tools, and complex experimental validation procedures. Although current studies on ASFV-specific T-cell immune responses and epitope identification are insufficient to meet vaccine development needs, continuous progress in T-cell immunology research in recent years has brought this goal closer to reality.

Porcine deltacoronavirus (PDCoV) is an emerging pathogen that causes severe, often fatal, diarrhea in suckling piglets and has zoonotic potential. Its nonstructural protein 12 (Nsp12), functioning as the RNA-dependent RNA polymerase (RdRp), is a central component of the viral replication–transcription complex and a critical target for host antiviral mechanisms. Here, we identified eukaryotic elongation factor 1 gamma (eEF1G) as a host interactor of PDCoV Nsp12 by immunoprecipitation-coupled mass spectrometry in IPEC-J2 cells. This interaction was confirmed by co-immunoprecipitation, pull-down assays, and confocal microscopy. Functional analyses involving siRNA knockdown and overexpression of eEF1G, combined with viral titration, strand-specific real-time quantitative PCR, and RNA immunoprecipitation assays, demonstrated that eEF1G directly binds to Nsp12. Knockdown of eEF1G significantly enhanced viral replication and increased negative-stranded RNA synthesis, whereas overexpression did not affect viral proliferation. Furthermore, eEF1G was found to bind PDCoV genomic RNA and competitively disrupt the interaction between Nsp12 and viral RNA, thereby impairing RdRp activity. Our results indicate that eEF1G acts as a novel host restriction factor that inhibits PDCoV replication by competing with Nsp12 for genomic RNA binding, ultimately blocking negative-stranded RNA synthesis. This study unveils a new antiviral mechanism and highlights a potential target for developing interventions against PDCoV.

Atypical porcine reproductive and respiratory syndrome (PRRS), which is caused by the Chinese highly pathogenic PRRS virus (HP-PRRSV), has resulted in large economic loss to the swine industry since its outbreak in 2006. However, to date, the region(s) within the viral genome that are related to the fatal virulence of HP-PRRSV remain unknown. In the present study, we generated a series of full-length infectious cDNA clones with swapped coding regions between the highly pathogenic RvJXwn and low pathogenic RvHB-1/3.9. Next, the in vitro and in vivo replication and pathogenicity for piglets of the rescued chimeric viruses were systematically analyzed and compared with their backbone viruses. First, we swapped the regions including the 5'UTR+ORF1a, ORF1b, and structural proteins (SPs)-coding region between the two viruses and demonstrated that the nonstructural protein-coding region, ORF1b, is directly related to the fatal virulence and increased replication efficiency of HP-PRRSV both in vitro and in vivo. Furthermore, we substituted the nonstructural protein (Nsp) 9-, Nsp10-, Nsp11- and Nsp12-coding regions separately; or Nsp9- and Nsp10-coding regions together; or Nsp9-, Nsp10- and Nsp11-coding regions simultaneously between the two viruses. Our results indicated that the HP-PRRSV Nsp9- and Nsp10-coding regions together are closely related to the replication efficiency in vitro and in vivo and are related to the increased pathogenicity and fatal virulence for piglets. Our findings suggest that Nsp9 and Nsp10 together contribute to the fatal virulence of HP-PRRSV emerging in China, helping to elucidate the pathogenesis of this virus.

The unfolded protein response (UPR) in the endoplasmic reticulum (ER) constitutes a critical component of host innate immunity against microbial infections. In this report, we show that porcine reproductive and respiratory syndrome virus (PRRSV) utilizes the UPR machinery for its own benefit. We provide evidence that the virus targets the UPR central regulator GRP78 for proteasomal degradation via a mechanism that requires viral glycoprotein GP2a, while both IRE1-XBP1s and PERK-eIF2α-ATF4 signaling branches of the UPR are turned on at early stage of infection. The activated effector XBP1s was found to enter the nucleus, but ATF4 was unexpectedly diverted to cytoplasmic viral replication complexes by means of nonstructural proteins nsp2/3 to promote viral RNA synthesis. RNAi knockdown of either ATF4 or XBP1s dramatically attenuated virus titers, while overexpression caused increases. These observations reveal attractive host targets (e.g., ATF4 and XBP1s) for antiviral drugs and have implications in vaccine development.

Influenza A virus (IAV) infection causes considerable morbidity and mortality worldwide, and the secondary bacterial infection further exacerbates the severity and fatality of the initial viral infection. Mitophagy plays an important role in host resistance to pathogen infection and immune response, while its role on pulmonary epithelial cells with viral and bacterial co-infection remains unclear. The present study reveals that the secondary Staphylococcus aureus infection significantly increased the viral and bacterial loads in human lung epithelial cells (A549) during the initial H1N1 infection. Meanwhile, the secondary S. aureus infection triggered more intense mitophagy in A549 cells by activating the PINK1/Parkin signaling pathway. Notably, mitophagy could contribute to the proliferation of pathogens in A549 cells via the inhibition of cell apoptosis. Furthermore, based on an influenza A viral and secondary bacterial infected mouse model, we showed that activation of mitophagy was conducive to the proliferation of virus and bacteria in the lungs, aggravated the inflammatory damage and severe pneumonia at the same time, and eventually decreased the survival rate. The results elucidated the effect and the related molecular mechanism of mitophagy in pulmonary epithelial cells following IAV and secondary S. aureus infection for the first time, which will provide valuable information for the pathogenesis of virus/bacteria interaction and new ideas for the treatment of severe pneumonia.