Fathalrhman Eisa Addoma Adam

Epstein–Barr virus (EBV), a common gamma herpesvirus, establishes a life‐long latent infection in the host to defend against innate immune recognition, which is closely related to a variety of malignant tumors, but its specific mechanism is unclear. BFRF3, an EBV‐encoded small capsid protein, is mainly involved in the assembly of the viral capsid structure and the maintenance of its stability. Here, we showed that BFRF3 can inhibit TNF‐α‐mediated NF‐кB promoter activation. Moreover, BFRF3 downregulates NF‐кB‐mediated promoter activation and transcription of inflammatory cytokines, including IL‐6 and IL‐8. Dual‐luciferase reporter assay demonstrated that BFRF3 restrains NF‐кB promoter activity at or below the p65 level, and coimmunoprecipitation analysis revealed that BFRF3 not only interacts with p65 but also binds to its critical truncated Rel homology domain (RHD) and transcriptional activation domain (TAD). However, BFRF3 does not affect the dimerization of p65‐p50, but overexpression of BFRF3 reduces the nuclear accumulation of p65, and the phosphorylation of p65 (Ser536) is repressed during BFRF3 transfection and EBV lytic infection, which promotes the proliferation of EBV. Overall, our study suggested that BFRF3 may play a crucial role in antiviral immunity to defend against EBV infection by inhibiting NF‐κB activity.

We studied the biological characterization of the developed functional synthetic recombinant adenoviruses, which showed a high degree of safety, thermostability, and genetic stability for up to 20 passages. It was demonstrated through both in vitro and in vivo testing that the immunogenicity of the proposed vaccine, which uses the T2A peptide from the Thosea asigna virus capsid protein supported by glycine and serine, helps with efficiency to generate a multicistronic vector, enables expression of two functional proteins in rAdv-ChGM-CSF-HN, and is superior to that of comparable vaccines.

According to the findings of a sheep breeding farm in Shaanxi, China, 2.53% (15/594) of sheep exhibited respiratory (clinical) symptoms such as dyspnoea, nasal discharge, wet cough, fever, and progressive emaciation. Although multi-drug treatment strategies (including ampicillin, tylosin, florfenicol, and ceftiofur) have been attempted to improve clinical outcomes, they have only been met with limited success, with a mortality rate of 40%. Ultimately, Aeromonas veronii (A. veronii) was identified as the causative pathogen for respiratory disease. The rates of symptomatic and asymptomatic sheep positive to A. veronii were 64.28% (95% CI 52.25–76.31%) and 8.02% (95% CI 6.96–9.08%), respectively. Pathogenicity tests demonstrated that the A. veronii is pathogenic to sheep and mice. The results of the antibiotic susceptibility tests revealed that the strain was sensitive to cefotaxime, gentamicin, and enrofloxacin and resistant to ampicillin, ceftiofur, amoxicillin, kanamycin, neomycin, streptomycin, tetracycline, florfenicol, and tylosin. We suggest that the combination of cefotaxime and gentamicin is an effective treatment based on the results of an antimicrobial susceptibility test, which exhibited good therapeutic efficacy. To the best of our knowledge, this is the first report in which pathogenic A. veronii has been documented as the cause of death in sheep in China. We concluded that pathogenic A. veronii poses a potential risk to the industry of sheep husbandry. This study’s findings can help guide prevention and treatment plans for A. veronii infection in sheep.

The worldwide spread of pathogenic Escherichia coli, together with the multidrug resistant linked with extended-spectrum β-lactamases (bla_CTX-M , bla_TEM and bla_OXA ), not only affect the health of animals and humans but also bring huge economic losses to animal husbandry. Despite the high levels of virulence present in many extended-spectrum beta-lactamases (ESBLs)-producing E. coli isolates, however, few studies have comprehensively assessed the pathogenicity of ESBLs-producing E. coli isolates. Thus, the aim of the present study was to investigate the presence of virulence genes in third-generation cephalosporin-resistant E. coli and to assess their pathogenicity and zoonotic potential. Previously, we identified 67 ESBLs-producing E. coli strains from sheep anal swabs in northwest China. In this study, we genotypically and phenotypically characterized isolates of E. coli that produce ESBLs. According to the VirulenceFinder and virulence factors database, all ESBLs-producing E. coli strains harboured a wide range of virulence genes. The ColV plasmid-related genes (hlyF, ompT, iss, iutA and cvaC) were present in 52 (77.6%) ESBLs-producing E. coli isolates. Surprisingly, quite a number of extraintestinal pathogenic E. coli virulence-related genes were detected in 62 (92.5%) of 67 isolates. A total of 33 serotypes and 37 sequence types (STs) were found in 67 ESBLs-producing isolates. ST10 is the most prevalent ST, which is represented by five strains. The cluster analysis showed that CC10 and CC23 were the common clonal complexes (CCs). Predominant serotypes were O8 (10%) and O9 (9%) followed by 6% each of O89, O101 and O185. Most sheep-origin ESBLs-producing E. coli held the highly pathogenic to human and displayed moderate-to-vigorous-intensity motor capacity. The ESBLs-producing E. coli isolates with numerous virulence-related genes were able to cause multiple infectious diseases in animal models (mice, neonatal rats and Galleria mellonella). To our knowledge, this study represents an important first step for a comprehensive characterization of pathogenicity and zoonotic potential of sheep-origin ESBLs-producing E. coli isolates. These findings may be of significant value for the identification of pathogenicity and zoonotic potential risks associated with sheep-origin ESBLs-producing E. coli.

Newcastle disease virus (NDV) which is pathogenic to chickens is characterized by dyspnea, diarrhea, nervous disorder and hemorrhages. However, the influence of different virulent NDV strain infection on the host gut microbiota composition is still poorly understood. In this study, twenty 21-day-old specific pathogen free (SFP) chickens were inoculated with either the velogenic Herts33 NDV strain, lentogenic La Sota NDV strain or sterile phosphate buffer solution (PBS). Subsequently, the fecal samples of each group were collected for 16S rRNA sequencing. The results showed that the gut microbiota were mainly dominated by Firmicutes, Bacteroidetes and Proteobacteria in both healthy and NDV infected chickens. NDV infection altered the structure and composition of gut microbiota. As compared to the PBS group, phylum Firmicutes were remarkably reduced, whereas Proteobacteria was significantly increased in the velogenic NDV infected group; the gut community structure had no significant differences between the lentogenic NDV infected group and the PBS group at phylum level. At genus level, Escherichia-Shigella was significantly increased in both the velogenic and lentogenic NDV infected groups, but the lactobacillus was only remarkably decreased in the velogenic NDV infected group. Collectively, different virulent strain NDV infection resulted in a different alteration of the gut microbiota in chickens, including a loss of probiotic bacteria and an expansion of some pathogenic bacteria. These results indicated that NDV strains with different virulence have different impacts on chicken gut microbiota and may provide new insights into the intestinal pathogenesis of NDV.

Pathogenic E. coli are among the most frequently isolated bacterial pathogens on large-scale sheep farms in China. Antibiotic use in wool sheep production is a risk factor for promoting the emergence of resistant E. coli. To reveal the differences of E. coli populations in sheep from different farming systems the antimicrobial resistance, virulence genes, biofilm formation, and phylogroups of 500 E. coli isolates obtained between September 2019 and December 2020 in northwest China from diarrheic infections of intensive farming and free-range sheep were analyzed. The antimicrobial susceptibility test for 12 classes of antimicrobial agents was determined using the broth microdilution susceptibility method, and PCR was used to detect the differences in virulence genes and phylogroups. Additionally, biofilm formation was determined using microtiter plate and slide agglutination methods. Among the 500 E. coli isolates, the majority of the isolates were multidrug resistant (75.4%) and carried at least one virulence gene (94.8%). We observed that 412 (82.4%), 360 (72.0%), and 266 (53.2%) are found to be resistant to sulfisoxazole, florfenicol, and tetracyclines, respectively. Resistance was also observed to mequindox (46.8%), ampicillin (43.6%), spectinomycin (38.6%), enrofloxacin (34.2%), ceftiofur (21.0%), gentamycin (20.4%), ceftazidime (17.8%), and polymyxin B (7.8%) but no resistance was found to meropenem. These results showed that strains from free-range subjects had fewer antibiotic resistance strains rather than sheep that were intensively farmed (P < 0.05). We observed fifteen virulence genes, of which etrA (n = 401, 80.2%) is the most common. In addition, EAEC (86.4%) is dominant among free-range sheep and EHEC (80.1%) is dominant among intensive farming. Among all virulence genes, the strongest correlation was found between etrA and papC gene (P < 0.001, OR = 455.68). Similarly, the strongest correlation was also found between eltA and sulfisoxazole (P < 0.001, OR = 877). Furthermore, the majority of the E. coli isolates belonged to phylogroup B1 (50.6%), followed by phylogroup C (20.6%), A (7.4%), E (7.4%), D (5.8%), B2 (1.6%), and F (1%). Interestingly, phylogroup B2 and D were all distributed in intensive farms. In addition, 33 (6.6%), 373 (74.6%), and 94 (18.8%) showed moderate, weak, and no connection biofilm formation ability, respectively. These data uncovered that wool sheep serve as a reservoir of pathogenic E. coli harboring multiple resistance phenotypes and virulence genes. The overlapping virulence-associated traits between IPEC and ExPEC indicated the zoonotic potential and safety threats of sheep food products. It is urgent to improve the proper use of antimicrobials in China as well as other countries.

Complement component 1 Q subcomponent-binding protein (C1QBP) has been shown to interact with the porcine circovirus type 2 (PCV2) Cap protein. Here, using yeast two-hybrid (Y2H) and co-immunoprecipitation assays, as well as laser confocal microscopy, the interaction between C1QBP and Cap was confirmed. Furthermore, overexpression of C1QBP in cells altered the intracellular location of Cap, which was observed using confocal microscopy and verified by detection of Cap in nuclear protein extracts in a Western blot assay. By inhibiting nuclear transport of Cap, overexpression of C1QBP downregulated PCV2 proliferation in PK-15 cells, as determined by quantitative polymerase chain reaction (qPCR). As C1QBP plays a similar role in a fusion of green fluorescent protein (GFP) with the Cap nuclear localisation signal (NLS) sequence, (CapNLS-GFP), we propose that the target site for C1QBP in Cap is possibly located in the NLS region. Considering all the results together, this study demonstrated that C1QBP interacts with the Cap NLS region, resulting in changes in the intracellular localisation of the Cap protein. We confirmed that overexpression of C1QBP inhibits the proliferation of PCV2, and this is possibly related to the function of C1QBP in controlling nuclear transport of Cap.