Mitochondria play pivotal roles in sustaining various biological functions including energy metabolism, cellular signaling transduction, and innate immune responses. Viruses exploit cellular metabolic synthesis to facilitate viral replication, potentially disrupting mitochondrial functions and subsequently eliciting a cascade of proinflammatory responses in host cells. Additionally, the disruption of mitochondrial membranes is involved in immune regulation. During viral infections, mitochondria orchestrate innate immune responses through the generation of reactive oxygen species (ROS) and the release of mitochondrial DNA, which serves as an effective defense mechanism against virus invasion. The targeting of mitochondrial damage may represent a novel approach to antiviral intervention. This review summarizes the regulatory mechanism underlying proinflammatory response induced by mitochondrial damage during viral infections, providing new insights for antiviral strategies.

Classical swine fever (CSF), caused by the classical swine fever virus (CSFV), results in significant economic losses to the swine industry in many countries. Vaccination represents the primary strategy to control CSF and the CSFV E2 protein is known as the major protective antigen. However, the E2 protein expressed or presented by different systems elicits distinct immune responses. In this study, we established a stable CHO cell line to express the E2 protein and delivered it using self-assembled ferritin nanoparticles (NPs). Subsequently, we compared the adaptive immune responses induced by the E2-ferritin NPs and the monomeric E2 protein produced by the CHO cells or a baculovirus expression system. The results revealed that the NP-delivered E2 protein elicited higher titers of neutralizing antibodies than did the monomeric E2 protein in pigs. Importantly, only the NP-delivered E2 protein significantly induced CSFV-specific IFN-γ-secreting cells. Furthermore, all the pigs inoculated with the E2-ferritin NPs were completely protected from a lethal CSFV challenge infection. These findings demonstrate the ability of the E2-ferritin NPs to protect pigs against the lethal CSFV challenge by eliciting robust humoral and cellular immune responses.

Mucosal vaccination offer an advantage over systemic inoculation from the immunological viewpoint. The development of an efficient vaccine is now a priority for emerging diseases such as COVID-19, that was declared a pandemic in 2020 and caused millions of deaths globally. Lactic acid bacteria (LAB) especially Lactobacillus are the vital microbiota of the gut, which is observed as having valuable effects on animals’ and human health. LAB produce lactic acid as the major by-product of carbohydrate degradation and play a significant role in innate immunity enhancement. LAB have significant characteristics to mimic pathogen infections and intrinsically possess adjuvant properties to enhance mucosal immunity. Increasing demand and deliberations are being substantially focused on probiotic organisms that can enhance mucosal immunity against viral diseases. LAB can also strengthen their host’s antiviral defense system by producing antiviral peptides, and releasing metabolites that prevent viral infections and adhesion to mucosal surfaces. From the perspectives of “one health” and the use of probiotics, conventional belief has opened up a new horizon on the use of LAB as antivirals. The major interest of this review is to depict the beneficial use of LAB as antivirals and mucosal immunity enhancers against viral diseases.

A novel circovirus called porcine circovirus type 4 (PCV4) was recently detected in pigs suffering from severe clinical diseases in Hunan province, China. There are few reports on the origin and evolution of PCV4, although some researchers have conducted epidemiological investigations of PCV4 and found that PCV4 is widespread in pigs. Based on the previous study, we detected PCV2 in farmed foxes and raccoon dogs with reproductive failure. To explore whether the PCV4 genome also exists in fur animals, we detected 137 cases admitted from fur animal farms in Hebei China between 2015 and 2020, which were characterized by inappetence, lethargy, depression, abortion, and sterility. The overall infection rate of PCV4 was 23.36% (32/137), including 20.37% (22/108) for raccoon dogs, 18.75% (3/16) for foxes, and 53.85% (7/13) for minks. Finally, five raccoon dog-origin PCV4 strains and one fox-origin PCV4 strain were sequenced in our study, whose nucleotide identities with other representative PCV4 strains varied from 96.5% to 100%. Phylogenetic analysis based on the complete genomes of PCV4 strains indicated a close relationship with those of PCV4 strains identified from pigs. To our knowledge, this is the first study to detect PCV4 in fur animals. Interestingly, we also identified PCV4 in a mixed farm (feeding pigs and raccoon dogs at the same time). In summary, our findings extend the understanding of the molecular epidemiology of PCV4 and provide new evidence for its cross-species transmission.

Pseudorabies virus (PRV) is one of the herpes viruses that can infect a wide range of animals including pigs, cattle, sheep, mice, and wild animals. PRV is a neurotropic alphaherpesvirus capable of infecting a variety of mammals. There is a rising interest in the targeted application of probiotic bacteria to prevent viral diseases, including PRV. In this study, the surface expression of enhanced green fluorescent protein (EGFP) on recombinant Lactiplantibacillus plantarum NC8 (rNC8) through the LP3065 LPxTG motif of Lactobacillus plantarum WCFS1 was generated. The surface expression was observed through confocal microscopy. Dendritic cell targeting peptides (DCpep) were also fused with LPxTG that help to bind with mouse DCs. The PRV-gD was cloned in LP3065 LPxTG, resulting in the generation of rNC8-LP3065-gD. Inactivated rNC8-LP3065-gD was administered intravenously in mice on days 1 and 7 at a dose of 200 µL (10⁹ CFU/mouse) for monitoring immunogenicity. Subsequently, a challenge dose of PRV TJ (10⁴ TCID₅₀) was administered intramuscularly at 14 days post-immunization. The survival rate of the immunized mice reached 80% (4/5) with no significant signs of illness. A significant rise in anti-gD antibodies was detected in the immunized mice by ELISA. Quantitative PCR (qPCR) results showed decreased viral loading in different body tissues. Flow cytometry of lymphocytes derived from mice spleen indicated an increase in CD3⁺CD4⁺ T cells, but CD3⁺CD8⁺ T cells were not detected. Moreover, it offers a model to delineate immune correlates with rNC8-induced immunity against swine viral diseases.

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.