The attenuated live vaccine strain W2512 provides protection against novel variant infectious bursal disease virus.

Infectious bursal disease virus (IBDV) causes an acute and highly contagious infectious disease characterized by severe immunosuppression, causing great economic losses to the poultry industry globally. Over the past 30 years, this disease has been well controlled through vaccination and strict biosafety measures. However, novel variant IBDV strains have emerged in recent years, posing a new threat to the poultry industry. Our previous epidemiological survey showed that few novel variant IBDV strains had been isolated from chickens immunized with the attenuated live vaccine W2512-, suggesting that this vaccine is efficacious against novel variant strains. Here, we report the protective effect of the W2512 vaccine against novel variant strains in SPF chickens and commercial yellow-feathered broilers. We found that W2512 causes severe atrophy of the bursa of Fabricius in SPF chickens and commercial yellow-feathered broilers, induces high levels of antibodies against IBDV, and protects chickens from infection with the novel variant strains via a placeholder effect. This study highlights the protective effect of commercial attenuated live vaccines against the novel IBDV variant and provides guidance for the prevention and control of this disease.

Retrospective detection and phylogenetic analysis of pseudorabies virus in dogs in China.

Pseudorabies virus (PRV), the causative agent of Aujeszky's disease, has gained increased attention in China in recent years as a result of a recent outbreak of pseudorabies. The causative agent has a wide spectrum of hosts, including pigs, cattle, sheep, dogs, cats, bats, bears, and even some avian species. Although dog-related cases of pseudorabies have been reported regularly, many cases are overlooked, and few PRV strains are isolated because death occurs rapidly after PRV infection and veterinarians often do not test for PRV in dogs. Here, we performed a retrospective detection of PRV in dogs from July 2017 to December 2018. We found that PRV (including gE-deleted strains, classical strains, and variant strains) is prevalent in dogs regardless of season and region and that the epidemic PRV strains in dogs share high sequence similarity with gC and gE genes of swine epidemic strains and commercial vaccine strains. Collectively, our findings underscore the importance of PRV surveillance in dogs, which is beneficial for understanding the epidemiology of PRV in dogs and assists in efforts aimed at effectively controlling this disease.

Tunable Adhesion of Different Cell Types Modulated by Thermoresponsive Polymer Brush Thickness.

Tunable adhesion of different cell types on well-defined surfaces has attracted common interests in the field of biomaterial science and surface engineering. Herein, we demonstrate a new strategy for the regulation of cell adhesion by simply controlling the thickness of thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes via surface-initiated atom transfer radical polymerization (ATRP). The adhesion of different cell types (4T1, HEK293, H9C2, HUVEC, and L929) can be easily modulated by varying the thickness of PNIPAAm brushes from 5.9 ± 1.0 nm (PN1) to 69.0 ± 5.0 nm (PN6). The fluorescent staining of different cell types on a variety of surfaces reveals that the thickness of PNIPAAm brushes would regulate the assembly of F-actin and the expression of vinculin and fibronectin, which are essential in regulating the adherent status of cells. Moreover, the cellular morphologies revealed that the adherent cells are well-spread, and multiple pseudopod extensions and protrusions can be observed at the margin of cells. This work provides a facile strategy for regulating tunable adhesion of different cell types, which may find applications in tissue engineering and regenerative medicine.

Novel variant infectious bursal disease virus diminishes FAdV-4 vaccination and enhances pathogenicity of FAdV-4.

Infectious bursal disease virus (IBDV) caused an acute and highly contagious infectious disease characterized by severe immunosuppression, causing considerable economic losses to the poultry industry globally. Although this disease was well-controlled under the widely use of commercial vaccines in the past decades, the novel variant IBDV strains emerged recently because of the highly immunized-selection pressure in the field, posting new threats to poultry industry. Here, we reported novel variant IBDV is responsible for a disease outbreak, and assessed the epidemic and pathogenicity of IBDV in this study. Moreover, we constructed a challenge model using Fowl adenovirus serotype 4 (FAdV-4) to study on the immunosuppressive effect. Our findings underscore the importance of IBDV surveillance, and provide evidence for understanding the pathogenicity of IBDV.

EBV promotes TCR-T-cell therapy resistance by inducing CD163+M2 macrophage polarization and MMP9 secretion.

BACKGROUND: Epstein-Barr virus (EBV) is a double-stranded DNA oncogenic virus. Several types of solid tumors, such as nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and lymphoepithelioma-like carcinoma of the lung, have been linked to EBV infection. Currently, several TCR-T-cell therapies for EBV-associated tumors are in clinical trials, but due to the suppressive immune microenvironment of solid tumors, the clinical application of TCR-T-cell therapy for EBV-associated solid tumors is limited. Figuring out the mechanism by which EBV participates in the formation of the tumor immunosuppressive microenvironment will help T cells or TCR-T cells break through the limitation and exert stronger antitumor potential. METHODS: Flow cytometry was used for analyzing macrophage differentiation phenotypes induced by EBV-infected and EBV-uninfected tumors, as well as the function of T cells co-cultured with these macrophages. Xenograft model in mice was used to explore the effects of M2 macrophages, TCR-T cells, and matrix metalloprotein 9 (MMP9) inhibitors on the growth of EBV-infected tumors. RESULTS: EBV-positive tumors exhibited an exhaustion profile of T cells, despite the presence of a large T-cell infiltration. EBV-infected tumors recruited a large number of mononuclear macrophages with CCL5 and induced CD163+M2 macrophages polarization through the secretion of CSF1 and the promotion of autocrine IL10 production by mononuclear macrophages. Massive secretion of MMP9 by this group of CD163+M2 macrophages induced by EBV infection was an important factor contributing to T-cell exhaustion and TCR-T-cell therapy resistance in EBV-positive tumors, and the use of MMP9 inhibitors improved the function of T cells cocultured with M2 macrophages. Finally, the combination of an MMP9 inhibitor with TCR-T cells targeting EBV-positive tumors significantly inhibited the growth of xenografts in mice. CONCLUSIONS: MMP9 inhibitors improve TCR-T cell function suppressed by EBV-induced M2 macrophages. TCR-T-cell therapy combined with MMP9 inhibitors was an effective therapeutic strategy for EBV-positive solid tumors.

Characterization and pathogenicity of infectious bursal disease virus in Southern China.

Infectious bursal disease virus (IBDV) is a widespread pathogen that induces immunosuppression in 3 to 6-wk-old chickens, casuing great threaten to the poultry industry worldwide. Previously, the very virulent IBDV (vvIBDV) was mainly prevalent in China. In recent years, the novel variant IBDV (nvIBDV) occurred in China. In this study, we isolated 30 IBDV strains of IBDV from vaccinated chicken flocks in 8 provinces of southern China. Among these isolates, vvIBDV group (13/30) and nvIBDV group (17/30) were identified according to the genome sequencing and phylogenic analysis. Moreover, HB2021-5 and GD2021-17 have pathologic characteristics with severe bursal lesions, as evidenced by necrosis, depletion of lymphocytes, and follicle atrophy. Our findings provide an important reference for understanding the epidemiological status and the evolution of IBDV.

Pathogenicity and molecular characterization of infectious bursal disease virus in China.

Infectious bursal disease virus (IBDV) caused an acute and highly contagious infectious disease, resulting in considerable economic losses in the world poultry industry. Although this disease was well-controlled under the widely use of commercial vaccines, the novel variant IBDV strain emerged due to the highly immunized-selection pressure in the field, posting new threats to poultry industry. Here, we reported the epidemic and pathogenicity of IBDV in Hubei Province from May to August 2020. We isolated 12 IBDV strains from the broiler flocks, including 9 novel variants, 2 very virulent strains and 1 medium virulent strain. Interestingly, we identified a series of changes of amino acid sites in the VP2. Further analysis indicated that the novel variant IBDV strains caused damage to bursa of fabricius and spleen, leading to immunosuppression. Our findings underscore the importance of IBDV surveillance, and provide evidence for understanding the evolution of IBDV.

Molecular Characterization Analysis of Prevalent Infectious Bronchitis Virus and Pathogenicity Assessment of Recombination Strain in China.

Avian coronavirus infectious bronchitis virus (IBV) is a respiratory pathogen of chickens, resulting in severe economic losses in the poultry industry. This study aimed to monitor and isolate the molecular identity of IBV in broiler flocks with respiratory symptoms in eight provinces of China. In total, 910 samples (oropharyngeal and cloacal mixed swabs) from broiler flocks showed IBV positive rates of 17.6% (160/910) using PCR assay. Phylogenetic analysis of the complete S1 genes of 160 IBV isolates was performed and revealed that QX-type (GI-19), TW-type (GI-7), 4/91-type (GI-13), HN08-type (GI-22),TC07-2-type (GVI-1), and LDT3-type (GI-28) exhibited IBV positive rates of 58.15, 25, 8.12, 1.86, 5.62, and 1.25%. In addition, recombination analyses revealed that the four newly IBV isolates presented different recombination patterns. The CK/CH/JS/YC10-3 isolate likely originated from recombination events between strain YX10 (QX-type) and strain TW2575-98 (TW-type), the pathogenicity of which was assessed, comparing it with strain GZ14 (TW-type) and strain CK/CH/GD/JR07-7 (QX-type). The complete S1 gene data from these isolates indicate that IBV has consistently evolved through genetic recombination or mutation, more likely changing the viral pathogenicity and leading to larger outbreaks in chick populations, in China.

Distribution and molecular characterization of avian infectious bronchitis virus in southern China.

Avian infectious bronchitis virus (IBV) is causing considerable economic losses in the world poultry industry. The main difficulty of prevention and control of IB disease is the numerous genotypes and serotypes. The genetic analysis of IBV was mainly based on the S1 gene which played an important role in infectivity. In the study, One hundred and thirty-nine strains of avian infectious bronchitis virus were isolated from chickens showing signs of disease in southern China during the period from April 2019 to March 2020. The nucleotide and amino acid sequences from the isolated field strains were compared to 22 published references. Nucleotide homologies ranged from 64.5% to 100% and amino acid homologies ranging from 70% to 99.8%. Six genotype IBV strains were co-circulating in southern China. QX-type was still the most dominant genotype. Alignment of nucleotide and amino acid sequences of S1 gene revealed that the substitutions, insertions and deletions are widely among isolated strains. Recombination analysis showed that there is a large number of recombinant strains amongst these isolates, forming new sub branches, subtypes and variants. Therefore, long-term continuing surveillance is necessary for IBV prevention and control.

Effect of Baicalin on Bacterial Secondary Infection and Inflammation Caused by H9N2 AIV Infection in Chickens.

H9N2 subtype avian influenza virus (H9N2 AIV) is a low pathogenic virus that is widely prevalent all over the world. H9N2 AIV causes immunosuppression in the host and often leads to high rates of mortality due to secondary infection with Escherichia. Due to the drug resistance of bacteria, many antibiotics are not effective in the treatment of secondary bacterial infection. Therefore, the purpose of this study is to find effective nonantibiotic drugs for the treatment of H9N2 AIV infection-induced secondary bacterial infection and inflammation. This study proves, for the first time, that baicalin, a Chinese herbal medicine, can regulate Lactobacillus to replace Escherichia induced by H9N2 AIV, so as to resolve the intestinal flora disorder. In addition, baicalin can effectively prevent intestinal bacterial translocation of SPF chickens' post-H9N2 AIV infection, thus inhibiting secondary bacterial infection. Furthermore, baicalin can effectively treat H9N2 AIV-induced inflammation by inhibiting intestinal structural damage, inhibiting damage to ileal mucus layer construction and tight junctions, improving antioxidant capacity, affecting blood biochemical indexes, and inhibiting the production of inflammatory cytokines. Taken together, these results provide a new theoretical basis for clinical prevention and control of H9N2 AIV infection-induced secondary bacterial infection and inflammation.