Porcine Circovirus 2 Infection Research Articles

Retinol binding protein 4 restricts PCV2 replication via selective autophagy degradation of viral ORF1 protein.

Autophagy is a highly conserved degradative process that has been linked to various functions, including defending host cells against pathogens. Although the involvement of autophagy in porcine circovirus 2 (PCV2) infection has become apparent, it remains unclear whether selective autophagy plays a critical role in PCV2 restriction. Here we show that retinol-binding protein 4 (RBP4), an adipokine for retinol carrier, initiates the autophagic degradation of PCV2 ORF1 protein. PCV2 infection increases RBP4 protein levels through MAPK-eIF4E axis in living cells. Ectopic expression of RBP4 or recombinant RBP4 treatment promotes the degradation of ORF1 protein. Mechanistically, RBP4 activates TRAF6 to induce K63-linked ubiquitination of ORF1, leading to SQSTM1/p62-mediated selective autophagy for degradation. Consequently, RBP4 deficiency increases viral loads and exacerbates the pathogenicity of PCV2 in vivo. Collectively, these results identify RBP4 as a key host restriction factor of PCV2 and reveal a previously undescribed antiviral mechanism against PCV2 in infected cells.

Situational analysis on porcine diseases: general risk assessment and prioritization of epizootic threats to biosecurity systems of pig establishments in the Russian Federation

The results of the situational analysis on porcine diseases in the Russian Federation and the expert assessment prioritizing the list of porcine pathogens significant for the pig industry of the country are presented. The method applied to analyse the expert estimates in the situational analysis allows for rapid assessment and interpretation of the situation with identification of priority diseases to be further addressed. The calculations demonstrated the sufficient degree of agreement among the experts (coefficient of concordance W = 0.61), and Pearson’s chi-squared test statistic χ2 = 51.33 (≥ 21.02607) indicated that the concordance is not random and the results can be used in subsequent studies. The specific features of epizootiology of the agents of African swine fever, classical swine fever, porcine reproductive and respiratory syndrome that can impact the effectiveness of biosecurity systems of pig establishments, as well as further ways for improving biosecurity management measures are discussed. The overall risk for the pig industry in the Russian Federation that is associated with external sources is currently characterized as permanently high, requiring maintaining risk management measures at the pig establishments by both the managerial staff of the establishments and the State Veterinary Service. It is recommended that biosecurity measures against external threats should focus on diseases such as African swine fever (weight λ = 0.52), porcine reproductive and respiratory syndrome (λ = 0.071), classical swine fever (λ = 0.068) and infections considered emerging for the Russian Federation (λ = 0.05) according to the weights based on the expert estimation results. The biosecurity systems of the establishments should equally address other threats significant for the pig industry of the country: swine enzootic pneumonia, porcine pleuropneumonia (Actinobacillus pleuropneumoniae), Aujeszky’s disease, streptococcosis (Streptococcus suis), porcine circovirus infection, foot-and-mouth disease, leptospirosis, transmissible gastroenteritis, cysticercosis (λ = 0.02…0.05). The improvement of the governmental policy for eradication of African swine fever, porcine reproductive and respiratory syndrome, classical swine fever (including the substantial modification of the existing official pig turnover control, zoning, diagnosis and prevention quality, as well as the implementation of biosecurity standards) is the most significant factor, without which the disease eradication perspective is questionable.

Development of recombinant capsid protein-based single serum dilution ELISA for sero-detection of porcine circovirus type 2 infection in pigs.

Porcine Circovirus 2 (PCV2) is the major causative agent of postweaning multisystemic wasting syndrome (PMWS) of swine and is one of the reasons for severe economic loss in swine industry. In India, there is a considerable prevalence rate of PCV2 infection in pig population, PCV2d being the most prominent genotype. Proper sero-diagnosis and sero-surveillance of the disease is formulated as an effective control measure. In this study, a recombinant capsid protein-based single serum dilution indirect ELISA was developed for determination of antibody titre of the infected pigs. The capsid protein (Cap) of PCV2d was produced in Saccharomyces cerevisiae cells and the capsid protein was purified by affinity chromatography. This recombinant protein was used as a coating antigen to develop a cost effective, highly sensitive and specific single serum dilution ELISA. The in-house developed ELISA was optimized to be used in a 1:200 single serum dilution. The developed ELISA along with a commercial ELISA kit were compared with a sensitive immuno-peroxidase assay (IPMA) by receiver-operating characteristics (ROC) test. Our results showed that the developed single serum dilution ELISA had a higher sensitivity and specificity in comparison to the commercial ELISA. The area under the ROC curve (AUC) also confirmed that the developed ELISA had a better overall diagnostic performance in comparison to the commercial ELISA kit.

Bacillus amyloliquefaciens B10 Alleviates the Immunosuppressive Effects of Deoxynivalenol and Porcine Circovirus Type 2 Infection.

As one of the most common mycotoxins, deoxynivalenol (DON) can contaminate a wide range of crops and foods. Porcine circovirus 2 (PCV2) is a kind of immunosuppressive virus, which can cause porcine circovirus associated disease (PCVD) in pig farms infected with PCV2. Pigs are extremely sensitive to DON, and PCV2-infected pig farms are often contaminated with DON. Our previous studies indicated that Bacillus amyloliquefaciens B10 (B10) has the potential to alleviate the toxicity of mycotoxins. The research was aimed at investigating the effects of Bacillus amyloliquefaciens B10 on the immunosuppressive effects caused by both DON and PCV2 infection. The results indicated that the expression of the PCV2 capsid protein CAP was significantly decreased after pretreatment with Bacillus amyloliquefaciens B10. Then, the effects of the Bacillus amyloliquefaciens B10 pretreatment on the type I interferon, antiviral protein and the antiviral signal pathway cGAS-STING was further investigated. The findings displayed that the expression of the type I interferon and antiviral protein were increased, while the IL-10 were decreased after pretreatment with Bacillus amyloliquefaciens B10. The inhibition of DON on the cGAS-STING signal pathway was relieved. Furthermore, it was found that this intervention effect was produced by inhibiting autophagy. In summary, Bacillus amyloliquefaciens B10 can mitigate the immunosuppressive effects of PCV2 and DON by inhibiting the production of autophagy.

Pathology and Molecular Diagnosis of Respiratory Disease Outbreak due to PCV-2 in a Pig Farm in Goa, India

Background: Pig farming is an important source of income and nutrition for rural farmers in Goa. Pig production is threatened by many infectious diseases. The present study reports a respiratory disease outbreak in a total of 200 pigs including adults and piglets with 40% mortality in a pig herd of Large white Yorkshire and crossbreds in South Goa during the winter period in January 2022. Method: The farm was visited and recorded clinical signs and post mortem findings and and samples were collected for bacterial isolation, PCR confirmation of bacterial and viral pathogens and histopathology. Result: The affected pigs showed high fever, reduced feed intake, staggering gate, huddling, difficulty in breathing, cough, and brown to greenish diarrhea followed by death within a span of 3 weeks. Major gross lesions were non-collapsed lungs with severe congestion and localized areas of consolidation, severe congestion of viscera, and enlargement, and presence of multifocal areas of necrosis in the liver. Histopathology of lungs focal or diffuse bronchointerstitial pneumonia and the lymphoid organs showed lymphoid depletion. Pasteruella multocida could be isolated from heart blood and tissues from 3 cases and PCR of the tissue DNA confirmed the presence of P. multocida and Porcine Circo Virus-2 (PCV-2) infection. The study confirms the presence of PCV-2 infection in pig herds in Goa for the first time. The acute mortality can be attributed to the co-infection of the herd with PCV-2 and P. multocida and sudden change in weather patterns with prevailing severe cold conditions during time of outbreak. Sequencing and Phylogenetic analysis of the PCV-2 ORF-2gene showed the PCV-2 virus from Goa is more related to isolates from southern Indian states.

Development of SYBR Green I-based quantitative PCR assay for identification of porcine circovirus 1, 2 and 3

Porcine Circovirus (PCV) includes Porcine Circovirus 1(PCV1), Porcine Circovirus 2 (PCV2) and Porcine Circovirus 3 (PCV3). In recent years, co-infection exists between PCV1, PCV2 and PCV3 serotypes. Therefore, it is particularly necessary to establish a fast, specific and sensitive SYBR Green I real-time quantitative PCR detection method for PCV1, PCV2 and PCV3. In this experiment, specific primers were selected and the reaction conditions were optimized. A real-time quantitative PCR identification method was established. The results showed the detection limits of this assay were 40.3 copies/μl for PCV1, 25.2 copies/μl for PCV2 and22.4 copies/ μl for PCV3. There was no cross-reactivity with swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine pseudorabies virus (PRV) and porcine parvovirus (PPV). The intra-assay and inter-assay coefficients of variation were less than 1%. The test results of 100 PCV suspected positive samples revealed that the PCV1, PCV2 and PCV3 singular infection rate was 10% (10/100), 64% (64/100) and 52% (52/100), respectively. The PCV1 and PCV2 co-infection rate was 8% (8/100), the PCV1 and PCV3 co-infection rate was 7% (7/100), the PCV2 and PCV3 co-infection rate was 26% (26/100), and the PCV1, PCV2 and PCV3 co-infection rate was 7% (7/100). This method has good specificity, sensitivity and stability. It provides a promising tool for rapid differential detection of PCV1, PCV2 and PCV3.

Revisiting Porcine Circovirus Infection: Recent Insights and Its Significance in the Piggery Sector.

Porcine circovirus (PCV), a member of the Circoviridae family within the genus Circovirus, poses a significant economic risk to the global swine industry. PCV2, which has nine identified genotypes (a-i), has emerged as the predominant genotype worldwide, particularly PCV2d. PCV2 has been commonly found in both domestic pigs and wild boars, and sporadically in non-porcine animals. The virus spreads among swine populations through horizontal and vertical transmission routes. Despite the availability of commercial vaccines for controlling porcine circovirus infections and associated diseases, the continuous genotypic shifts from a to b, and subsequently from b to d, have maintained PCV2 as a significant pathogen with substantial economic implications. This review aims to provide an updated understanding of the biology, genetic variation, distribution, and preventive strategies concerning porcine circoviruses and their associated diseases in swine.

Porcine Circovirus 2 Increases the Frequency of Transforming Growth Factor-β via the C35, S36 and V39 Amino Acids of the ORF4.

Porcine circovirus 2 (PCV2) is one of the most important endemic swine pathogens, inducing immunosuppression in pigs and predisposing them to secondary bacterial or viral infections. Our previous studies show that PCV2 infection stimulated pig intestinal epithelial cells (IPEC-J2) to produce the secretory transforming growth factor-β (TGF-β), which, in turn, caused CD4+ T cells to differentiate into regulatory T cells (Tregs). This may be one of the key mechanisms by which PCV2 induces immunosuppression. Here, we attempt to identify the viral proteins that affect the TGF-β secretion, as well as the key amino acids that are primarily responsible for this occurrence. The three amino acids C35, S36 and V39 of the ORF4 protein are the key sites at which PCV2 induces a large amount of TGF-β production in IPEC-J2 and influences the frequency of Tregs. This may elucidate the regulatory effect of PCV2 on the Tregs differentiation from the perspective of virus structure and intestinal epithelial cell interaction, laying a theoretical foundation for improving the molecular mechanism of PCV2-induced intestinal mucosal immunosuppression in piglets.

Development of an immunoassay for the detection of Porcine circovirus infection

Development of an immunoassay for the detection of Porcine circovirus infection

Development of a TaqMan-Probe-Based Multiplex Real-Time PCR for the Simultaneous Detection of African Swine Fever Virus, Porcine Circovirus 2, and Pseudorabies Virus in East China from 2020 to 2022

African swine fever virus (ASFV), porcine circovirus 2 (PCV2), and pseudorabies virus (PRV) are important DNA viruses that cause reproductive disorders in sows, which result in huge losses in pig husbandry, especially in China. The multiplex qPCR assay could be utilized as a simultaneous diagnostic tool for field-based surveillance and the control of ASFV, PCV2, and PRV. Based on the conserved regions on the p72 gene of ASFV, the Cap gene of PCV2, the gE gene of PRV, and the porcine endogenous β-Actin gene, the appropriate primers and probes for a multiplex TaqMan real-time PCR test effective at concurrently detecting three DNA viruses were developed. The approach demonstrated high specificity and no cross-reactivity with major pathogens related to swine reproductive diseases. In addition, its sensitivity was great, with a detection limit of 101 copies/L of each pathogen, and its repeatability was excellent, with intra- and inter-group variability coefficients of <2%. Applying this assay to detect 383 field specimens collected from 2020 to 2022, the survey data displayed that the ASFV, PCV2, and PRV single infection rates were 22.45%, 28.46%, and 2.87%, respectively. The mixed infection rates of ASFV + PCV2, ASFV + PRV, PCV2 + PRV, and ASFV + PCV2 + PRV were 5.22%, 0.26%, 1.83%, and 0.26%, respectively. Overall, the assay established in this study provides an effective tool for quickly distinguishing the viruses causing sow reproductive disorders, suggesting its huge clinical application value in the diagnosis of swine diseases.

Expression of PCV2d Capsid Protein in Escherichia coli and its Evaluation for Serodiagnosis of Porcine Circovirus Infection

Expression of PCV2d Capsid Protein in Escherichia coli and its Evaluation for Serodiagnosis of Porcine Circovirus Infection

Ensuring veterinary well-being and productivity of pigs with an immunotropic drug

The purpose of this work is to realize the productive qualities of young pigs by increasing the effectiveness of specific prevention of infectious diseases. The object of the study was 45 pigs of the Landrace breed from 14 to 171 days of age, divided according to the principle of pairs of analogues into 3 groups of 15 heads. The animals of the 1st experimental group were injected with the immunotropic drug PigStim-V in a dose of 1.0 ml per head twice at the age of 14 and 21 days in order to stimulate nonspecific resistance of the body and increase the effectiveness of specific prevention of infectious diseases intramuscularly at the age of 14 and 21 days. Moreover, the second injection was carried out simultaneously with immunization against type 2 porcine circovirus infection. The tested immunotropic drug PigStim-V was administered to animals of the 2nd experimental group once, at a dose of 1.0 ml per head at the age of 21 days simultaneously with a commercial vaccine against porcine circovirus. Animals of the 3rd group served as biological control. The results of the study confirm the effectiveness of the use of the immunotropic drug PigStim-V as an adjuvant in the vaccination of pigs. Both single and double intramuscular injection of PigStim-V increases the titer of specific antibodies against porcine circovirus infection and against α, β and ε toxins of the microorganism Clostridium perfringens, prevents and increases the effectiveness of therapy of diseases of non-infectious etiology, stimulates growth. A more pronounced positive effect is observed with the double administration of an immunotropic drug.

Development and validation of TaqMan probe-based real-time polymerase chain reaction for detection of Porcine Circovirus 2

Pigs are under constant threat from many infectious diseases and post-weaning multisystemic syndrome (PWMS) is one among them. The syndrome is caused by the Porcine Circovirus 2 (PCV2) which belongs to the Circoviridae family. Because the symptoms of PCV2 infection and other porcine infectious illnesses, especially porcine reproductive and respiratory syndrome (PRRS) overlap, diagnosis of the former based on clinical indicators could be challenging. A study was conducted to develop a TaqMan real-time polymerase chain reaction (PCR) for the detection of PCV2 genotypes prevalent in Kerala. Primers and TaqMan probes based on the ORF2 nucleotide sequences of the PCV2 prevalent in Kerala were designed. On testing, it was observed that the TaqMan real-time PCR was not able to detect the PCV2genotypes prevalent in Kerala. However, the designed primers (but not the probe) were able to detect these genotypes. Hence, another TaqMan assay specific for detection of 2d was designed as that genotype was predominant in Kerala. The detection limit estimated using the cloned template was found to be 310 copies of the viral genome. The assay was more sensitive in detecting the virus compared to conventional PCR.

Development of a TaqMan-Probe-Based Multiplex Real-Time PCR for the Simultaneous Detection of Porcine Circovirus 2, 3, and 4 in East China from 2020 to 2022.

Porcine circovirus disease (PCVD) caused by porcine circovirus (PCV) is an important swine disease that is characterized by porcine dermatitis, nephropathy syndrome, and reproductive disorders in sows. However, disease caused by PCV2, PCV3, or PCV4 is hard to distinguish, so a rapid and sensitive detection method is urgently needed to differentiate these three types. In this study, four pairs of specific primers and the corresponding probes for PCV 2, -3, and -4, and porcine endogenous gene β-Actin as the positive internal reference index, were designed to establish a TaqMan multiplex real-time PCR (qPCR) assay for the simultaneous differential diagnosis of different types of viruses. The results showed that this assay has good specificity and no cross-reactivity with other important porcine viral pathogens. Furthermore, it has high sensitivity, with a detection limit of 101 copies/μL, and good reproducibility, with intra- and inter-group coefficients of variation below 2%. Subsequently, 535 clinical samples of suspected sow reproductive disorders collected from Shandong, Zhejiang, Anhui, and Jiangsu provinces from 2020 to 2022 were analyzed using the established assay. The results showed that the individual positive rates of PCV2, PCV3, and PCV4 were 31.03%, 30.09%, and 30.84%, respectively; the mixed infection rates of PCV2 and PCV3, PCV2 and PCV4, and PCV3 and PCV4 were 31.03%, 30.09%, and 30.84%, respectively; the mixed infection rate of PCV2, PCV3, and PCV4 was 28.22%. This indicated that this assay provides a convenient tool for the rapid detection and differentiation of PCV2, PCV3, and PCV4 in pig farms in East China. Our findings highlight that there are different types of porcine circovirus infection in pig farms in East China, which makes pig disease prevention and control difficult.

Aspects of the formation of post-vaccination immunity against porcine circovirus infection and its correction

Relevance. Prevention of circovirus diseases in swine management is one of the urgent problems in the industry. The article provides data on the results of the use of two regimens for administering vaccines against circovirus infection to piglets according to immunological, biochemical and zootechnical indicators.Methods. The work was carried out on piglets, which were vaccinated with "Ingelvak CircoFLEX" vaccine (Germany) against circovirus at the age of 21 days, in the experimental group it was administered together with "leukocytic lysate" obtained from donors hyperimmunized with this vaccine. Evaluation of the effectiveness of post-vaccination immunity formation was carried out based on the results of immunological, biochemical, zootechnical and statistical studies.Results. It was established that when the vaccination was combined with the introduction of «leukocytic lysate» from hyperimmunized donors, the number of piglets with a positive test for the presence of viral neutralizing antibodies was 79.30–82.33%, in the control — 67.80–71.60%, as a result of changes in the leukocytic blood pool within the normal limits. In piglets of experimental group blood concentration of total protein and albumins starting from 60-day age exceeds control level by 7.73–8.68 and 17.84–30.27% respectively. In the experimental group, compared with the control group, the co-storage of animals is increased by 9.02%, the live weight of piglets at the end of the nursery period is increased by 12.88 kg, or 31.85%, based on one head and the value of medium increases in live weight — by 90 g, or 26.01%.

TGF-β from the Porcine Intestinal Cell Line IPEC-J2 Induced by Porcine Circovirus 2 Increases the Frequency of Treg Cells via the Activation of ERK (in CD4+ T Cells) and NF-κB (in IPEC-J2).

Porcine circovirus 2 (PCV2) causes immunosuppression. Piglets infected with PCV2 can develop enteritis. Given that the gut is the largest immune organ, however, the response of the gut's immune system to PCV2 is still unclear. Here, IPEC-J2 cells with different treatments were co-cultured with PBMC or CD4+ T cells (Transwell). Flow cytometry and Western blotting revealed that PCV2-infected IPEC-J2 increased the frequency of CD4+ T cells among piglets' peripheral blood mononuclear cells (PBMCs) and caused CD4+ T cells to undergo a transformation into Foxp3+ regulatory T cells (Treg cells) via activating CD4+ T ERK. Cytokines production and an inhibitor assay showed that the induction of Tregs by PCV2-infected IPEC-J2 was dependent on TGF-β induced by PCV2 in IPEC-J2, which was associated with the activation of NF-κB. Taken together, PCV2-infected IPEC-J2 activated NF-κB to stimulate the synthesis of TGF-β, which enhanced the differentiation of CD4+ T cells into Treg cells through the activation of ERK in CD4+ T cells. This information sheds light on PCV2's function in the intestinal immune system and suggests a potential immunosuppressive mechanism for PCV2 infection.

Efficacy Studies of a Trivalent Vaccine Containing PCV-2a, PCV-2b Genotypes and Mycoplasma hyopneumoniae When Administered at 3 Days of Age and 3 Weeks Later against Porcine Circovirus 2 (PCV-2) Infection.

Four studies under preclinical and clinical conditions were performed to evaluate the efficacy of a new trivalent vaccine against Porcine circovirus 2 (PCV-2) infection. The product contained inactivated PCV-1/PCV-2a (cPCV-2a) and PCV-1/PCV-2b (cPCV-2b) chimeras, plus M. hyopneumoniae inactivated cell-free antigens, which was administered to piglets in a two-dose regime at 3 days of age and 3 weeks later. The overall results of preclinical and clinical studies show a significant reduction in PCV-2 viraemia and faecal excretion, and lower histopathological lymphoid lesions and PCV-2 immunohistochemistry scores in vaccinated pigs when compared to non-vaccinated ones. Furthermore, in field trial A, a statistically significant reduction in the incidence of PCV-2-subclinical infection, an increase in body weight from 16 weeks of age to slaughterhouse and an average daily weight gain over the whole period (from 3 days of age to slaughterhouse) was detected in the vaccinated group when compared to the non-vaccinated one. Circulation of PCV-2a in field trial A, and PCV-2b plus PCV-2d in field trial B was confirmed by virus sequencing. In conclusion, a double immunization with a cPCV-2a/cPCV-2b/M. hyopneumoniae vaccine was efficacious against PCV-2 infection by reducing the number of histopathological lymphoid lesions and PCV-2 detection in tissues, serum, and faeces, as well as reducing losses in productive parameters.

Porcine Circovirus type 2 infected myocardial tissue transcriptome signature

The goal of this study was to compare the global gene expression profile in cardiac tissues of pig infected with porcine circovirus 2 (PCV2) to that of healthy cells. Since PCV2 infection causes severe cardiovascular lesions, the myocardial tissue model was chosen for this study. In High-throughput transcriptome analysis, DESeq2 and CLC genomics workbench analyses revealed a total of 196 significantly differentially expressed genes (DEGs) (p-value < 0.05). Furthermore, 194 transcripts were upregulated, while only two were downregulated (HSPA6 and DNAJA1), with fold changes ranging from 16.293 to −10.002. Among the KEGG canonical pathways targeted by the DEGs in the functional analysis, adrenergic signalling in cardiomyocytes, Cardiac Muscle Contraction, Hypertrophic Cardiomyopathy (HCM), and Dilated Cardiomyopathy (DCM) tends to be enriched. The differentially expressed highly connected (DEHC) biomarker genes in pathogenicity of PCV2 infection, such as LDB3, MYOZ2, CASQ2, TNNT2, MLC2V, MYBPC3, ACTC1, TCAP, TNNI3, TRDN, CSRP3, MYL3, RYR2, LMOD2, MYH7, etc., were identified using protein–protein interaction (PPI) network analysis. The study might provide detailed information on the dysregulated genes and biological pathways in infected myocardial tissues that may be essential for PCV2-related heart pathology.

PCV2 and PRV Coinfection Induces Endoplasmic Reticulum Stress via PERK-eIF2α-ATF4-CHOP and IRE1-XBP1-EDEM Pathways

Porcine circovirus 2 (PCV2) and pseudorabies virus (PRV) are two important pathogens in the pig industry. PCV2 or PRV infection can induce endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). However, the effect of PCV2 and PRV coinfection on the ERS and UPR pathways remains unclear. In this study, we found that PRV inhibited the proliferation of PCV2 mainly at 36 to 72 hpi, while PCV2 enhanced the proliferation of PRV in the middle stage of the infection. Notably, PRV is the main factor during coinfection. The results of the transcriptomic analysis showed that coinfection with PCV2 and PRV activated cellular ERS, and upregulated expressions of the ERS pathway-related proteins, including GRP78, eIF2α, and ATF4. Further research indicated that PRV played a dominant role in the sequential infection and coinfection of PCV2 and PRV. PCV2 and PRV coinfection induced the ERS activation via the PERK-eIF2α-ATF4-CHOP axis and IRE1-XBP1-EDEM pathway, and thus may enhance cell apoptosis and exacerbate the diseases.

Coinfection of Porcine Circovirus 2 and Pseudorabies Virus Enhances Immunosuppression and Inflammation through NF-κB, JAK/STAT, MAPK, and NLRP3 Pathways

Porcine circovirus 2 (PCV2) and pseudorabies virus (PRV) are economically important pathogens in swine. PCV2 and PRV coinfection can cause more severe neurological and respiratory symptoms and higher mortality of piglets. However, the exact mechanism involved in the coinfection of PRV and PCV2 and its pathogenesis remain unknown. Here, porcine kidney cells (PK-15) were infected with PCV2 and/or PRV, and then the activation of immune and inflammatory pathways was evaluated to clarify the influence of the coinfection on immune and inflammatory responses. We found that the coinfection of PCV2 and PRV can promote the activation of nuclear factor-κB (NF-κB), c-Jun N-terminal protein kinases (JNK), p38, and nod-like receptor protein 3 (NLRP3) pathways, thus enhancing the expression of interferon-γ (IFN-γ), interferon-λ1 (IFN-λ1), interferon-stimulated gene (ISG15), interleukin 6 (IL6), and interleukin 1β (IL1β). Meanwhile, PCV2 and PRV also inhibit the expression and signal transduction of IFN-β, tumor necrosis factor α (TNFα), and the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway. In addition, PCV2 and PRV infection can also weaken extracellular-signal-regulated kinase (ERK) activity. These results indicate that the regulations of cellular antiviral immune responses and inflammatory responses mediated by NF-κB, JAK/STAT, mitogen-activated protein kinase (MAPK), and NLRP3 pathways, contribute to immune escape of PCV2 and PRV and host antiviral responses.