Lin Yi

In the original publication, there was a mistake in Figure 1B(b,c) as published

Recently, the emergence of HP-PRRSV (Highly Pathogenic porcine reproductive and respiratory syndrome virus) and the exacerbation of mixed infections of PRRSV and PCV have resulted in significant economic losses for the Chinese pig industry. This study collected a total of 226 samples suspected of infection with the aforementioned viruses from diverse pig farms in seven urban districts of central and northern Guangdong Province between 2020 and 2022. The positive rates of PRRSV, PCV2, and PCV3 in the samples were 33.2%, 37.6%, and 7.5%, respectively, and there were various mixed-infection scenarios present in the samples. This study successfully isolated multiple strains of PRRSV2 and PCV2 from their positive samples, and obtained the gene sequences of six PCV3 (ORF1 + ORF2) from samples. The associated sequences obtained were subjected to bioinformatic analysis and revealed the following:Predominantly prevalent strains of PRRSV in Guangdong Province include HP-PRRSV and NADC30-like variants, whereas PCV2 is primarily represented by the 2b and 2d subtypes. Specifically, the amino acid variation patterns exhibited by the PRRSV GP5 and NSP2 proteins of the strains sg_2108, qy_2008, and fs_2108 under environmental selective pressure are remarkably similar to the characteristics of Highly Pathogenic PRRSV; thus, it is inferred that they may possess higher virulence. The detected PCV3 strains were predominantly concentrated within the PCV3a-IM branch. All PRRSV strains involved in this study are wild-type-PRRSV (wt-PRRSV), comprising three recombinant strains and seven highly virulent strains. Among these strains, the ORF1a gene exhibited the highest variability in their genomes. Environmental selective pressure may enhance the virulence and immune evasion capabilities of PRRSV and drive mutations in the Cap proteins of PCV2 and PCV3. Conversely, PCV2 and PCV3 strains demonstrated greater stability in genetic evolution. In conclusion, this study enhances the epidemiological data regarding PRRSV, PCV2, and PCV3 in Guangdong Province, China, and is significant for the surveillance, prevention, and active control of these three diseases.

The occurrence of classical swine fever (CSF) poses a significant threat to the global swine industry. Developing an effective and safe vaccine is crucial for preventing and controlling CSF. Here, we constructed self-assembled ferritin nanoparticles fused with the classical swine fever virus (CSFV) E2 protein and a derived B cell epitope (Fe-E2B) using a baculovirus expression system (BVES), demonstrating enhanced immunogenicity. Furthermore, we provide a detailed evaluation of the immunological efficacy of the FeE2B in rabbits. The results showed that robust and sustained antibody responses were detected in rabbits immunized with the Fe-E2B nanoparticle vaccine, comparable to those elicited by commercially available vaccines. Additionally, we demonstrated that the vaccine effectively activated crucial immune factors IFN-γ and IL-4 in vivo, increasing their levels by 1.41-fold and 1.39-fold, respectively. Immunization with Fe-E2B enabled rabbits to avoid viremia and stereotypic fever after CSFV challenge. In conclusion, this study highlights the potential of ferritin nanoparticles as antigen-presenting carriers to induce robust immune responses, proposing a candidate vaccine strategy for the prevention and control of CSF.

Interferon (IFN) is a cell-secreted cytokine possessing biological activities including antiviral functioning, immune regulation, and others. Interferon-alpha (IFN-α) mainly derives from plasmacytoid dendritic cells, which activate natural killer cells and regulate immune responses. IFN-α responds to the primary antiviral mechanism in the innate immune system, which can effectively cure acute infectious diseases. Pseudorabies (PR) is an acute infectious disease caused by pseudorabies virus (PRV). The clinical symptoms of PRV are as follows: reproductive dysfunction among pregnant sows and high mortality rates among piglets. These pose a severe threat to the swine industry. Related studies show that IFN-α has broad applications in preventing and treating viral diseases. Therefore, a PRV mouse model using artificial infection was established in this study to explore the pathogenic effect of IFN-α on PRV. We designed a sequence with IFN-α4 (M28623, Genbank) and cloned it on the lentiviral vector. CHO-K1 cells were infected and identified using WB and RT-PCR; a CHO-K1 cell line with a stable expression of the recombinant protein PoIFN-α was successfully constructed. H&E staining and virus titer detection were used to investigate the recombinant protein PoIFN-α’s effect on PR in BALB/c mice. The results show that the PoIFN-α has a preventive and therapeutic impact on PR. In conclusion, the recombinant protein can alleviate symptoms and reduce the replication of PRV in vivo.

African swine fever virus (ASFV) is a pathogen to cause devastating and economically significant diseases in domestic and feral swine. ASFV mainly infects macrophages and monocytes and regulates its replication process by affecting the content of cytokines in the infected cells. There is a limited understanding of host gene expression and differential profiles before and after ASFV infection in susceptible cells. In this study, RNA-seq technology was used to analyze the transcriptomic change in PAMs infected with ASFV at different time points (0 h, 12 h, 24 h). As a result, a total of 2748, 1570, and 560 genes were enriched in group V12 h vs. MOCK, V24 h vs. MOCK, and V24 h vs. V12 h, respectively. These DEGs (differentially expressed genes) in each group were mainly concentrated in the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways related to innate immunization and inflammation, including the NF-κB signaling pathway, Toll-like receptor signaling pathway, TNF signaling pathway, IL-17 signaling pathway, cytokine-cytokine receptor interaction, and chemokine signaling pathway. Furthermore, the increased levels of IL-1β, TNF-α, IKKβ, CXCL2, and TRAF2 and decreased level of IκBα were validated through the qPCR method. These results suggested that ASFV infection can activate the NF-κB signaling pathway in the early stage. In general, this study provides a theoretical basis for further understanding the pathogenesis and immune escape mechanism of ASFV.

Porcine circovirus type 2 (PCV2) is capable of causing porcine circovirus-associated disease (PCVAD) and is one of the major threats to the global pig industry. The nucleocapsid protein Cap encoded by the PCV2 ORF2 gene is an ideal antigen for the development of PCV2 subunit vaccines, and its N-terminal nuclear localization sequence (NLS) structural domain is essential for the formation of self-assembling VLPs. In the present study, we systematically expressed and characterized full-length PCV2 Cap proteins fused to dominant T and B cell antigenic epitopes and porcine-derived CD154 molecules using baculovirus and found that the Cap proteins fusing epitopes were still capable of forming virus-like particles (VLPs). Both piglet and mice experiments showed that the Cap proteins fusing epitopes or paired with the molecular adjuvant CD154 were able to induce higher levels of humoral and cellular responses, particularly the secretion of PCV2-specific IFN-γ and IL-4. In addition, vaccination significantly reduced clinical signs and the viral load of PCV2 in the blood and tissues of challenged piglets. The results of the study provide new ideas for the development of a more efficient, safe and broad-spectrum next-generation PCV2 subunit vaccine.

Classical swine fever (CSF), caused by the classical swine fever virus (CSFV), is a highly contagious and fatal viral disease, posing a significant threat to the swine industry. Heat shock protein 90 kDa alpha class A member 1 (HSP90AA1) is a very conservative chaperone protein that plays an important role in signal transduction and viral proliferation. However, the role of HSP90AA1 in CSFV infection is unknown. In this study, we found that expression of HSP90AA1 could be promoted in PK-15 and 3D4/2 cells infected by CSFV. Over-expression of HSP90AA1 could inhibit CSFV replication and functional silencing of HSP90AA1 gene promotes CSFV replication. Further exploration revealed that HSP90AA1 interacted with CSFV NS5A protein and reduced the protein levels of NS5A. Since NS5A has an important role in CSFV replication and is closely related to type I IFN and NF-κB response, we further analyzed whether HSP90AA1 affects CSFV replication by regulating type I IFN and NF-κB pathway responses. Our research found HSP90AA1 positively regulated type I IFN response by promoting STAT1 phosphorylation and nuclear translocation processes and promoted the nuclear translocation processes of p-P65. However, CSFV infection antagonizes the activation of HSP90AA1 on JAK/STAT and NF-κB pathway. In conclusion, our study found that HSP90AA1 overexpression significantly inhibited CSFV replication and may inhibit CSFV replication by interacting with NS5A and activating JAK/STAT and NF-κB signaling pathways. These results provide new insights into the mechanism of action of HSP90AA1 in CSFV infection, which abundant the candidate library of anti-CSFV.

Foot-and-mouth disease (FMD) is a serious disease affecting the global graziery industry. Once an epidemic occurs, it can lead to economic and trade stagnation. In recent decades, FMD has been effectively controlled and even successfully eradicated in some countries or regions through mandatory vaccination with inactivated foot-and-mouth disease vaccines. Nevertheless, FMD still occurs in some parts of Africa and Asia. The transmission efficiency of foot-and-mouth disease is high. Both disease countries and disease-free countries should always be prepared to deal with outbreaks of FMD. The development of vaccines has played a key role in this regard. This paper summarizes the development of several promising vaccines including progress and design ideas. It also provides ways to develop a new generation of vaccines for FMDV and other major diseases.

Since the beginning of the 21st century, humans have experienced three coronavirus pandemics, all of which were transmitted to humans via animals. Recent studies have found that porcine deltacoronavirus (PDCoV) can infect humans, so swine enteric coronavirus (SeCoV) may cause harm through cross-species transmission. Transmissible gastroenteritis virus (TGEV) and PDCoV have caused tremendous damage and loss to the pig industry around the world. Therefore, we analyzed the genome sequence data of these two SeCoVs by evolutionary dynamics and phylogeography, revealing the genetic diversity and spatiotemporal distribution characteristics. Maximum likelihood and Bayesian inference analysis showed that TGEV could be divided into two different genotypes, and PDCoV could be divided into four main lineages. Based on the analysis results inferred by phylogeography, we inferred that TGEV might originate from America, PDCoV might originate from Asia, and different migration events had different migration rates. In addition, we also identified positive selection sites of spike protein in TGEV and PDCoV, indicating that the above sites play an essential role in promoting membrane fusion to achieve adaptive evolution. In a word, TGEV and PDCoV are the past and future of SeCoV, and the relatively smooth transmission rate of TGEV and the increasing transmission events of PDCoV are their respective transmission characteristics. Our results provide new insights into the evolutionary characteristics and transmission diversity of these SeCoVs, highlighting the potential for cross-species transmission of SeCoV and the importance of enhanced surveillance and biosecurity measures for SeCoV in the context of the COVID-19 epidemic.

Endoplasmic reticulum-associated degradation (ERAD) is highly conserved in yeast. Recent studies have shown that ERAD is also ubiquitous and highly conserved in eukaryotic cells, where it plays an essential role in maintaining endoplasmic reticulum (ER) homeostasis. Misfolded or unfolded proteins undergo ERAD. They are recognized in the ER, retrotranslocated into the cytoplasm, and degraded by proteasomes after polyubiquitin. This may consist of several main steps: recognition of ERAD substrates, retrotranslocation, and proteasome degradation. Replication and transmission of the virus in the host is a process of a “game” with the host. It can be assumed that the virus has evolved various mechanisms to use the host’s functions for its replication and transmission, including ERAD. However, until now, it is still unclear how the host uses ERAD to deal with virus infection and how the viruses hijack the function of ERAD to obtain a favorable niche or evade the immune clearance of the host. Recent studies have shown that viruses have also evolved mechanisms to use various processes of ERAD to promote their transmission. This review describes the occurrence of ERAD and how the viruses hijack the function of ERAD to spread by affecting the homeostasis and immune response of the host, and we will focus on the role of E3 ubiquitin ligase.