Search Results (1,473)

Gammaretroviruses are ubiquitous pathogens, often associated with the induction of neoplasia, especially leukemia, lymphoma, and sarcoma, and with a propensity to target the germline. The latter trait has left extensive evidence of their infectious competence in vertebrate genomes, the human genome being no exception. Despite the continuing activity of gammaretroviruses in mammals, including Old World monkeys, apes, and gibbons, humans have apparently evaded novel infections by the virus class for the past 30 million years or so. Nevertheless, from the 1970s onward, cell culture studies repeatedly discovered gammaretroviral components and/or virus replication in human samples. The last novel ‘human’ gammaretrovirus, identified in prostate cancer tissue, culminated in the XMRV frenzy of the 2000s. In the end, that discovery was shown to be due to lab contamination with a murine gammaretrovirus. Contamination is also the likely source of the earlier findings. Complementation between genes of partially defective endogenous proviruses could have been another source of the virions observed. However, the capacity of many gammaretroviruses to replicate in human cell lines, as well as the presence of diverse infectious gammaretroviral species in our animal companions, for instance in mice, cats, pigs, monkeys, chickens, and bats, does not make a transmission to humans an improbable scenario. This review will summarize evidence for, or the lack of, gammaretrovirus infections in humans in the past, present, and near future. Aspects linked to the probabilities of novel gammaretrovirus infections in humans, regarding exposure risk in connection to modern lifestyle, geography, diet, and habitat, together with genetic and immune factors, will also be part of the review, as will be the estimated consequences of such novel infections. Full article

Background/Objectives: Inadequate characterization of protective antigens poses a significant challenge to the development of vaccines for African swine fever (ASF), particularly for antigen-dependent formulations such as subunit, mRNA, and recombinant viral vector vaccines. To address this, we aimed to screen African swine fever virus (ASFV) antigens and enhance their immunogenicity using a nanoparticle delivery platform. Methods: Here, six ASFV antigens (p30, p54, pE120R, pH124R, pE184L, and CD2v) were purified and used to immunize pigs individually. The effects of antibodies induced by these six antigens on ASFV replication or hemadsorption was evaluated in primary porcine alveolar macrophages (PAMs). These six antigens were, respectively, conjugated to ferritin via SpyTag/SpyCatcher to prepare six ferritin nanoparticles. A cocktail of the six mixed antigens or a cocktail of the six mixed nanoparticles was used to immunize pigs separately, and the differences in induced humoral and cellular immune responses were compared. Results: Antibodies generated against p30, p54, pE120R, pH124R, and pE184L in immunized pigs significantly inhibited ASFV replication in PAMs, while anti-CD2v antibodies specifically obstructed the hemadsorption of ASFV. Notably, immunization with a cocktail of these antigen-conjugated nanoparticles elicited a stronger virus-inhibitory antibody response compared to immunization with a cocktail of antigen monomers. Furthermore, nanoparticle immunization induced robust cellular immunity, evidenced by elevated serum IFN-γ, increased numbers of ASFV-specific IFN-γ-secreting cells, and an expanded CD8⁺ T cell population. Conclusions: Our study identifies a set of promising ASFV antigen candidates and demonstrates that ferritin nanoparticle delivery synergistically enhances both humoral and cellular immune responses against ASFV, providing a rational strategy for multi-antigen ASF vaccine design. Full article

The reasons for disease outbreaks caused by Actinobacillus pleuropneumoniae (APP) in vaccinated pigs are often unknown and remain a challenge for farmers and veterinarians. One hypothesis for APP vaccine failure is the timing of APP vaccination during field or vaccine-induced viremia with Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), which may negatively affect the immune response to APP vaccination. In this study, fattening pigs were vaccinated with a modified live vaccine (MLV) against PRRSV either at the beginning of the fattening period (group G1) or six weeks later (group G2). All pigs were vaccinated against APP five days after the start of fattening, which coincided with MLV-PRRSV viremia in G1. Within both G1 and G2, four subgroups of pigs (n = 10) were vaccinated with three different APP vaccines or remained unvaccinated to assess serological responses to various APP antigens. MLV-PRRSV viremia had no significant effect on APP-ApxII (p = 0.127), APP-LPS (p = 0.120), or opsonophagocytic antibody responses on day 40 of fattening. Lung lesion scores at slaughter were significantly higher (p = 0.004) in pigs from G2 (1.82 ± 2.38) compared with those from G1 (0.65 ± 0.88). All APP vaccines elicited presumably protective opsonophagocytic antibodies. In conclusion, no effects of MLV-PRRSV viremia on serological responses following APP vaccination were observed. Full article

The world is divided into seven regional pools based on the serotype distribution and geographical spread of the foot-and-mouth disease (FMD) virus. The Republic of Korea (ROK) belongs to Pool 1, where serotypes O, A, and Asia1 are endemic. Recently, the risk of incursions by the O/CATHAY topotype has increased in Pool 1, raising concerns about its potential introduction into the ROK. To assess the protective effectiveness of three commercial FMD vaccine strains—O1/Manisa + O/3039, O/Primorsky, and O1/Campos—currently used in the ROK against this topotype, an animal challenge experiment was conducted. Three treatment groups (n = 4 in each) of pigs received a single 2 mL injection of one of the vaccines at 8–10 weeks of age, and the other group (n = 2) served as the control. All pigs were challenged with the O/HKN/5/2019 virus (O/CATHAY topotype) at 21 days post-vaccination. All vaccines conferred protective effects, with O1/Campos demonstrating the highest efficacy by inducing fewest clinical signs and significantly reducing virus shedding in the treated groups compared with those in the control group. These findings suggest O1/Campos may serve as an emergency measure; nevertheless, the development of a vaccine specifically targeting the O/CATHAY topotype is warranted. Full article

Porcine circovirus 2 (PCV2) is a DNA virus that is classified in the genus Circovirus of the Circoviridae family, which is a causative agent of Porcine Circovirus-Associated disease (PCVAD). PCVAD continues to cause substantial losses in global pig farming, with PCV2d being the prevalent genotype worldwide, including in Vietnam. In this study, we focused on generating a recombinant PCV2d Cap protein fused to the GCN4pII motif (Cap2d-pII) in a plant-based system and evaluating its immunogenicity. The Cap2d-pII gene was cloned into a plant expression vector and introduced into Agrobacterium tumefaciens for transient expression in Nicotiana benthamiana leaves. Western blot analysis confirmed the high accumulation of the Cap2d-pII protein, which was purified by Immobilized affinity chromatography and used for immunizing mice. ELISA and immunoperoxidase monolayer assay results demonstrated that immunization with the recombinant protein elicited robust humoral and cellular immune responses. At 56 days after immunization, mice vaccinated with the Cap2d-pII protein generated PCV2d-specific IgG titers and IFN-γ responses that were consistent with those in mice receiving the commercial inactivated vaccine. These observations confirm that the plant-expressed Cap2d-pII antigen effectively activates both antibody- and T cell-mediated immune pathways. Collectively, this study identifies the Cap2d-pII protein as a promising plant-derived vaccine candidate for the development of effective and affordable PCV2d subunit vaccines. Full article

Influenza A virus (IAV) continues to present a threat to public health, highlighting the need for safe and multi-target antivirals. In this study, anti-influenza activity, airborne transmission blocking capacity, and immunomodulatory effects of Cnidium monnieri polysaccharides (CMP) were evaluated. Cytotoxicity in A549 cells was assessed by CCK-8 (CC₅₀ = 8.49 mg/mL), antiviral efficacy against A/California/04/2009 (CA04) by dose–response (EC₅₀ = 1.63 mg/mL), and the stage of action by time-of-addition assays (pre-, co-, post-treatment). A guinea pig model infected with CA04 was used for testing the effect of pre-exposure CMP on transmission, with readouts including nasal-wash titers, seroconversion, lung index, and tissue titers (EID₅₀). RT-qPCR was employed to quantify the mRNA expression levels of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, in lung tissue, while Western blot analysis was performed to assess the expression and phosphorylation status of key proteins involved in the NF-κB signaling pathway. CMP suppressed viral replication in vitro within non-cytotoxic ranges, and pre-treatment—rather than co- or post-treatment—significantly reduced titers and cytopathic effect, consistent with effects at pre-entry steps and/or host priming. In vivo, pre-exposure CMP lowered nasal shedding, reduced aerosol transmission (3/6 seroconverted vs. 6/6 controls), decreased lung indices, and diminished tissue viral loads; IAV was undetectable in trachea at 7 days post-infection in pre-exposed animals, and nasal-turbinate titers declined relative to infection controls. Moreover, during in vivo treatment in mice, CMP significantly suppressed the levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in lung tissue. This effect was mechanistically associated with CMP-mediated regulation of the NF-κB signaling pathway, leading to attenuation of inflammatory responses. These data indicate that CMP combines a favorable in vitro safety and efficacy profile with inhibition of airborne spread in vivo, supporting further mechanistic, pharmacokinetic, and fractionation studies toward translational development. Full article

Enteric infections remain a major health and economic challenge in swine production, with outcomes determined not only by pathogen virulence but also by the complex interplay between host genetics, immune competence, and the intestinal microbiota. This review synthesises current knowledge on host–pathogen genomic interactions in pigs, with a focus on resilience mechanisms against enteric diseases in swine. For this purpose, 103 articles were used as information sources, retrieved through structured keyword searches in PubMed. The review first addresses host genetic factors, highlighting genomic variants and quantitative trait loci associated with resistance or resilience to viral and bacterial pathogens such as porcine epidemic diarrhoea virus (PEDV) or Escherichia coli. Next, the key factors of the immune system to confer protection are also reviewed, emphasising the role of innate and adaptive responses in controlling each pathogen and disclosing the contribution of regulatory networks that balance pathogen clearance. Finally, the last section of the review is devoted to exploring current knowledge in the involvement of the microbiota in resilience against enteric pathogens, mostly, but not exclusively, enteric bacteria. In this sense, competitive exclusion is a concept which has gained attention in recent years. The review pinpoints and discusses the state of the art about how the microbial community provides colonisation resistance, shapes immune development, and influences pathogen fitness within the intestinal niche. As final perspectives, the review explores future drivers in the genetic immune and microbiota resistance. By bridging host genomic data with functional insights into immunity and microbial ecology, this review underscores the potential of multi-omics approaches to enhance resilience against enteric infections in pigs and advance sustainable swine health management. Full article

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major cause of economic loss in the swine industry, and highly pathogenic variants such as NADC34-like PRRSV highlight the need for antiviral strategies that complement vaccination. In this field study, we evaluated the efficacy of AlimenWOW, a rottlerin–lipid formulation, in grower–finisher pigs under commercial conditions using AI-based respiratory monitoring. A total of 2000 pigs were assigned to four groups: AlimenWOW G1 (PRRSV-stable source farm), AlimenWOW G2 (PRRSV-unstable source farm), Control 1 (antibiotic), and Control 2 (antipyretic). Respiratory Health Status (ReHS) and a derived Clinical Cough Index (CCI = 100 − ReHS) were continuously recorded with SoundTalks^®, and oral fluid PRRSV load, serology, clinical outcomes, and productivity were assessed over 4 weeks. AlimenWOW G2 showed a marked improvement in ReHS from severely compromised baseline values to levels comparable with healthy status, while both control groups remained low; CCI was significantly lower in AlimenWOW G2 than in controls from day 14 onward (p ≤ 0.0001). AlimenWOW treatment was associated with reduced PRRSV titers in oral fluid, lower mortality and wasting rates, and improved feed conversion with lower feed costs compared with controls. These findings indicate that AlimenWOW, integrated with AI-based acoustic monitoring, can improve respiratory health and mitigate PRRSV-associated clinical and economic losses, supporting its use as a complementary tool in PRRSV control programs. Full article

Foot-and-mouth disease virus (FMDV) infection elicits sustained, high-level interleukin-10 (IL-10) secretion in cattle and pigs, which correlates with lymphopenia and immunosuppression. We previously showed that macrophages are the principal source of IL-10 during FMDV infection in mice, but the viral trigger and host pathways remained unknown. In the present study, we examined whether the FMDV structural protein VP3 regulates IL-10 expression. To this end, a eukaryotic VP3 expression vector was transfected into porcine alveolar macrophages (3D4/21 cells), and IL-10 expression together with related signaling pathways was interrogated by qRT-PCR, ELISA, Western blot, co-immunoprecipitation (Co-IP), confocal microscopy, and luciferase reporter assays. The results showed that VP3 significantly increased IL-10 mRNA and protein levels (p < 0.001) in a time-dependent manner. Mechanistically, VP3 promoted phosphorylation of PI3K, AKT, and mTOR; this effect was abolished by the PI3K inhibitor LY294002, which also abrogated VP3-induced IL-10 secretion (p < 0.05). Furthermore, VP3 upregulated mRNA expression of STAT3, ATF1, and CREB (p < 0.05) and enhanced IL-10 promoter activity. The STAT3 inhibitor Stattic reduced IL-10 secretion by 22% (p < 0.05). Co-IP and confocal microscopy confirmed direct binding of VP3 to PI3K in the cytoplasm. In conclusion, FMDV VP3 induces IL-10 overexpression by directly activating the PI3K/AKT-mTOR signaling pathway, thereby elucidating a key mechanism of FMDV-induced immunosuppression. Full article

Porcine epidemic diarrhea virus (PEDV) is an enteric alphacoronavirus that causes severe diarrhea and high mortality in neonatal pigs, leading to substantial economic loss in the porcine industry. Previous studies have primarily focused on the spike protein because of its role in viral entry and induction of neutralizing antibody responses. However, accumulating evidence indicates that other viral components also contribute to host immune modulation and pathogenesis. This review summarizes the current knowledge on PEDV structural proteins, with an emphasis on membrane proteins as regulators of porcine innate immune responses. The molecular characteristics and intracellular localization of membrane proteins were described, and the reported effects on interferon signaling, inflammatory pathways, and cellular stress responses were examined. Findings from related coronaviruses were incorporated to highlight the conserved features and virus-specific differences in membrane protein-mediated host modulation. Available evidence suggests that membrane protein-associated interference with innate immune signaling may contribute to intestinal immune dysregulation and disease severity in neonatal piglets. The implications of these observations on PEDV pathogenesis and intervention strategies are also discussed. By shifting attention from spike-centered frameworks to structural protein-driven host interactions, this review highlights membrane proteins as an underexplored but biologically relevant factor in porcine coronavirus research. Full article

Background: Porcine circovirus type 2 (PCV2) remains one of the most important pathogens that infects swine, causing considerable economic losses worldwide. PCV2 vaccines are commercially available, and the development of experimental vaccines that could confer better protection against emerging genotypes is underway. The expression of virus-like particles (VLPs) carrying different PCV2 capsid (Cap) peptides in E. coli was recently reported. These chimeric particles were adjuvated with an oil-in-water emulsion with polymer and induced different titers of serum IgG in BALB/c mice after a single subcutaneous injection. The aim of this study was to assess the immune response and protective efficacy elicited by VLPs carrying the PCV2b Cap carboxy-terminal peptide in the target species. Methods: Domestic pigs (Sus scrofa domesticus) were immunized intramuscularly with 25 μg of adjuvated chimeric VLPs on days 0 and 14 and challenged on day 28 with a PCV2b Mexican isolate. PCV2 peptide-specific IgG seroconversion, serum cytokines, viral load in nasal swabs and organs, and histopathological score were determined. Results: IgG levels peaked 28 days post-immunization. Interleukin-12 and -18 and interferon-gamma increased 21 days after immunization. In addition, genomic material of PCV2 was detected in nasal swabs from one specimen on day 7, two specimens on day 14, and two specimens on day 21 following viral challenge. Finally, histological lesions were not less severe in immunized specimens compared to non-vaccinated/challenged specimens. Conclusions: These results suggest that immunization with chimeric VLPs could contribute to controlling viral shedding in pig herds where a PCV2b genotype is most prevalent. Full article

Porcine cytomegalovirus, more accurately classified as porcine roseolovirus (PCMV/PRV), was shown to be pathogenic in the context of xenotransplantation. Transmission of PCMV/PRV to non-human primates receiving hearts or kidneys from virus-positive pigs significantly reduced the survival time of the recipients. PCMV/PRV was also transmitted to the first human recipient of a pig heart transplant and contributed to the patient’s death. Although PCMV/PRV is highly prevalent in all pig breeds and wild boars, including slaughterhouse pigs, no infections or diseases have been reported in healthy, ill, or immunocompromised humans, suggesting that this virus is not zoonotic and should therefore be classified as xenozoonotic. This indicates that this virus is not zoonotic and must be classified as xenozoonotic. Moreover, it remains unclear whether PCMV/PRV is capable of infecting human cells in vitro. To address this question, human 293T cells resistant to hygromycin were co-cultured with porcine fallopian tube (PFT) cells producing PCMV/PRV. After hygromycin selection, the remaining human cells showed no evidence of infection. Because herpesviruses are generally considered to be species-specific—a notion that has been shown to be not entirely correct—it was also investigated whether PCMV/PRV can infect mouse cells using the same approach. Similarly, no infection was observed. Since the target cells employed in both assays had a reduced capacity to resist viral infection, the findings strongly suggest that PCMV/PRV is unable to infect human or mouse cells, which are equipped with functional antiviral mechanisms. This is supported by findings from the patient who received the first pig heart transplantation. Full article

This study integrates data on the prevalence, infection dynamics and risks associated with African swine fever virus (ASFV) outbreaks in Croatian wild boar during 2023–2024. Although the overall ASFV DNA prevalence in Croatia was 0.24%, the highest prevalence (2.29% in 2023 and 4.69% in 2024) was recorded in Vukovar-Srijem County. Genetic typing identified ASFV genotype II, subgroup 19, consistent with strains isolated from domestic pigs in Croatia and circulating in neighboring countries. Anti-ASFV specific antibodies were detected in 10.34% of wild boar tested in counties with previously reported DNA findings. In Vukovar-Srijem County, 4.60% of wild boar were positive for both, ASFV DNA and antibodies, suggesting ongoing virus infection, whereas the proportion of boar positive only for antibodies was 5.75%, indicating survival of acute infection. Statistical analysis revealed an increase in ASFV DNA detection from 2023 to 2024 (p = 0.043), with a higher prevalence in carcasses than in hunted animals (p = 0.001), highlighting the need for passive monitoring. While gender showed no statistical significance, a higher infection rate was observed in older animals (p = 0.001). The identified course of infection involved spillover events between domestic pigs and wild boar, with a significant anthropogenic influence. Full article

Porcine deltacoronavirus (PDCoV) is a newly discovered porcine intestinal coronavirus that can pose a significant threat to the global commercial swine industry. We established an enzyme-linked immunosorbent assay (ELISA) detection method for the detection of PDCoV antibodies, based on the recombinant nucleocapsid (N) protein expressed using a baculovirus system. The assay was validated using positive and negative serum samples obtained from experimentally immunized rabbits and demonstrated an absence of cross-reactivity with either transmissible gastroenteritis virus (TGEV) or porcine epidemic diarrhea virus (PEDV). The recombinant PDCoV N protein antigen dilution (0.8 μg/mL), sample serum (1:400), and the enzyme-labeled secondary antibody (1:50) were used in this assay. The cut-off value was 0.355, without cross-reactivity including TGEV and PEDV. The ELISA method shows good sensitivity (96.67%), specificity (85.51%), and reproductivity (CV < 10%). We utilized the method to detect PDCoV antibodies in 600 pig serums collected from Zhejiang Province in the last four years (2021–2024). The results showed significant differences in antibody levels between regions and considerable fluctuation in positivity rates across the four-year period. As shown in the results, we developed a sensitive and specific ELISA method for detecting anti-PDCoV N antibodies, which provides a rapid and reliable diagnostic tool for PDCoV surveillance and control. This assay demonstrates significant potential for both epidemiological investigations and commercial applications in swine disease management. Full article

Porcine circovirus type 2 (PCV2), a widely distributed immunosuppressive virus, causes substantial economic losses in the global swine industry. C1QTNF6 has emerged as a novel immunoregulatory factor attracting increasing research interest due to its dual roles in both pro-inflammatory and antiviral immune responses. However, the role of C1QTNF6 in regulating PCV2 replication remains poorly characterized. Here, we analyzed C1QTNF6 expression patterns and identified its highly specific expression in placental tissues in both humans and pigs. We then overexpressed C1QTNF6 and conducted RNA sequencing analysis. Remarkably, 68 upregulated genes were identified, and most of them were interferon-stimulated genes (ISGs), including MX2 and ISG15. Functional enrichment analysis revealed that these genes were primarily associated with defense response to viruses and antiviral innate immune response. Subsequently, experimental data show that PCV2 infection significantly suppressed inflammatory responses and markedly downregulated the expression of C1qtnf6, MX2, and IFIT2. Moreover, experimental data indicated that C1QTNF6 inhibits PCV2 replication by targeting ISGs, while restoring MX2 expression. To verify whether C1QTNF6-MX2 antiviral axis mediates this antiviral effect, we constructed an MX2 overexpression plasmid and demonstrated that MX2 overexpression indeed significantly suppressed PCV2 replication. Together, these results provide important insights into PCV2-host interactions and the development of novel antiviral strategies. Full article