Porcine circovirus type 2 (PCV2) is one of the major threats to pig farms worldwide. Although PCV2 has been identified to promote IL-10 production, the detailed regulatory roles of PCV2 Rep for IL-10 production remain unclear. Herein, we first found that PCV2 Rep, rather than PCV1 Rep, enhanced IL-10 expression at the later phase of PCV2 infection in porcine alveolar macrophages (PAMs). Furthermore, we found that PCV2 Rep directly activated the p38-MAPK pathway to promote transcription factors NF-κB p50 and Sp1 binding to the il10 promoter, but PCV1 Rep did not. During PCV2 infection, however, PCV2 Rep promoted the binding activities of NF-κB p50 and Sp1 with the il10 promoter only at the later phase of PCV2 infection, since Rep proteins only expressed at the later phase of the infection. Moreover, silence of the thymine DNA glycosylase (TDG), a Rep-binding protein, significantly reduced the binding activities of NF-κB p50 and Sp1 with il10 promoter, resulting in the reduction of IL-10 production in PCV2-inoculated PAMs at the later phase of infection. Taken together, our results demonstrate that Rep proteins enhance IL-10 production during PCV2 infection of PAMs via activation of p38-MAPK pathways, in which host TDG is a critical mediator.

This study evaluated the prevalence of BRV infection and its impact on the health of dairy cows at different growth stages, with a particular focus on milk-fed calves. BRV was detected in rectal swabs via RT–qPCR. In the total sample of 2400 dairy cows examined at three farms, 103 (4.29%) were found to be positive for BRV. Similarly, of the 480 milk-fed calves, 70 (14.58%) were also found to be positive for BRV. Negative binomial regression analysis revealed that older farms had higher average BRV positivity rates than new farms did and that the BRV positivity rate was higher in autumn than in the other three seasons. Additionally, BRV positivity rates gradually decreased as calf age increased. In milk-fed calves, BRV positivity was positively correlated with morbidity and mortality and negatively correlated with ADG and ADGPR. These findings provide valuable insights for farm management, particularly for older farms, highlighting the detrimental effects of BRV infection on milk-fed calves and underscoring the importance of targeted control strategies to reduce BRV prevalence and optimize dairy production efficiency.

Porcine circovirus 2 (PCV2) is one of the most widespread immunosuppressive viruses, impairing the protective efficacy of vaccines in pig herds. Previous studies have shown that PCV2 infection reduces the generation of immune memory and antibody secretion induced by vaccination in hosts. In this study, we used single-cell mRNA sequencing of mice splenic cells to show that PCV2 infection decelerates the differentiation of light zone germinal center (GC) B cells into memory B cells and plasma cells. We found that, although PCV2 infection led to lymphocyte depletion in the spleens of mice, the remaining splenic B cells were activated by the infection. The percentage of naïve B cells in PCV2-infected mice decreased mainly due to differentiation rather than death. Meanwhile, the percentages of memory B cells and plasma cells increased without significant enhancement of functional gene expression. Focusing on the GC B cells, we found that PCV2 infection activated the proliferation of dark zone GC B cells, but not the differentiation of light zone GC B cells. Furthermore, the transcriptional level of Prdm1 was not significantly altered by PCV2 infection, and the level of Bach2 was dramatically reduced. Further analysis showed that the interactions between light zone GC B cells and dendritic cells, macrophages, and follicular helper T cells were weakened in the spleens of PCV2-infected mice. In conclusion, this study found that PCV2 infection impairs the differentiation of B cells into functional memory B cells and plasma cells. This may be an important and previously unrecognized reason why PCV2 infection impairs vaccine efficiency.

Optimal calf rearing is fundamental for ensuring efficient milk production. Bovine coronavirus (BCoV) poses a significant threat to calf health and leads to substantial economic losses in the dairy industry. However, the mechanisms by which the intestinal mucosal microbiome regulates the host immune response during infection remain unclear. In this study, we constructed a high-resolution map of the jejunal mucosal microenvironment in BCoV-infected calves. Our findings revealed that BCoV infection led to severe microbial dysbiosis, characterized by a marked reduction in Phocaeicola coprophilus (formerly known as Bacteroides coprophilus ) and decreased secondary bile acid, especially deoxycholic acid (DCA). Concurrently, enrichment of harmful microbiota correlated with increased arachidonic acid metabolites. At the host level, BCoV infection altered the composition of jejunal mucosal cells and affected metabolic and immune-related pathways. The differentiation of CD4⁺ T cells played a central role in the jejunum’s response to BCoV infection. By integrating these metabolic alterations with dynamic host cellular responses, we suggested a putative that DCA deficiency might contribute to the pathological polarization of CD4 ⁺ T cells toward a Th17 phenotype while suppressing Treg differentiation. These findings suggest that restoring the Phocaeicola coprophilus -affected bile acid transformation might represent a promising therapeutic strategy for BCoV infection.

Canine parvovirus-2 (CPV-2) and canine distemper virus (CDV) are two highly infectious and pathogenic pathogens that harm canids and various carnivores, and often cause co-infections in clinical settings. Although commercial attenuated live vaccines against CPV-2 and CDV have been widely used to prevent these viral infections, there are still issues of biosafety and insufficient protection against new variants, thus requiring novel vaccines. In this study, we developed a recombinant pseudovirus expression system based on the CPV-2 full-length infectious clone, and found that the recombinant CPV-2 pseudovirus expressing CDV H protein could efficiently protect dogs against both CPV-2 and CDV infections. We first designed a recombinant pseudovirus vector based on the CPV-2 backbone and established a stable cell system for the production of CPV-2 recombinant pseudoviruses carrying foreign genes. These pseudoviruses preserved the morphology and particle size of native CPV-2, while maintaining hemagglutination activity against porcine erythrocytes, and demonstrated the ability to effectively infect permissive cells to express the harbored foreign gene. Next, we produced a recombinant CPV-2 pseudovirus expressing CDV H protein, and the CPV–CDV recombinant pseudovirus induced effective cellular and humoral immune responses in dogs. The serum from CPV–CDV immunized dogs could effectively neutralize CPV-2 and CDV infections in susceptible cells. Importantly, CPV–CDV completely protected dogs against challenge with CPV-2 and CDV. In summary, we have successfully developed a stable production system of recombinant CPV-2 pseudoviruses, which has great potential for development as a vaccine platform.