Dysbiosis of the gut microbiota maybe exacerbate orf pathology by promoting inflammatory immune responses.

Orf is a contagious disease caused by the epitheliotropic orf virus (ORFV) that mainly affects goats and sheep. Orf occurs worldwide and can cause great losses to livestock production. Mounting evidence has shown that gut microbiota plays a pivotal role in shaping the immune responses of the host and thus affecting the infection process of a wide range of pathogens. However, it is unclear whether gut microbiota plays a role during orf development. In this study, we exploited asymptomatic ORFV-carrier goats to explore the potential effects of gut microbiota on orf pathogenesis. The results showed that antibiotics-induced gut microbiota disruption significantly aggravated orf, as indicated by the greater disease severity and higher percentage of animals manifesting clinical orf symptoms. Further analysis suggested IL-17-induced excessive neutrophil accumulation in the diseased lips was potentially responsible for the tissue pathology. In addition, skin γδT cells may be an important source of IL-17. In conclusion, our study showed that the gut microbiota of ORFV-carrier goats plays a central role in controlling inflammatory pathology during ORFV infection, partly through suppressing IL-17-mediated local proinflammatory immune responses. This finding can provide help for elucidating the pathogenesis of orf and also suggests an efficient strategy to minimize the inflammatory pathology by maintaining a healthy gut microbiota during orf development.

Compositional and Functional Comparisons of the Microbiota in the Colostrum and Mature Milk of Dairy Goats.

Goat milk is essential for the initial development of kids by providing a great source of commensal bacteria. In this study, we analyzed the microbiota of the milk of 30 healthy Saanen dairy goats. The 30 samples comprised 15 colostrum and 15 mature milk samples, collected from three different farms of Shaanxi Province. Colostrum samples were collected daily for five days post-delivery and mature milk was collected on the 7th, 10th, 20th, 30th, and 40th days. The result showed that microbial alpha diversity was higher in the mature milk compared with that in the colostrum. Linear discriminant analysis effect size (LEfSe) was performed to detect differentially abundant taxa in colostrum and goat milk. According to taxonomy results, Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the predominant bacteria phyla in both colostrum and mature milk. In addition, lactation stage noticeably influenced the composition of milk microbiota. Specifically, Novosphingobium, Brachybacterium, Psychrobacter, Lactobacillus, Yersinia, Roseateles, Rothia, Sanguibacter, Cloacibacterium, Variovorax, Sphingobacterium, and Coxiella were enriched in the colostrum, while Georgenia, Peptostreptococcus, Bacteroidales, Yaniella, Planomicrobium, Cloacibacterium, Azospirillum, Turicibacter, Cupriavidus, Herbaspirillum, Rhodobacteraceae, and Aeromonadales were the dominant genera in the mature milk. The enriched metabolic functions of the goat milk microbiota were predicted by PICRUSt and classified by KEGG pathway. Moreover, the abundances of environmental information processing, cellular processes pathway, genetic information processing pathway, organismal systems pathway, and metabolism pathway were significantly different between microbiota of colostrum and mature milk. Altogether, our study disclosed the significant difference between the microbial communities of colostrum and mature milk and provided grounds for further research in dairy microbiology.

The matrix protein of vesicular stomatitis virus inhibits host-directed transcription of target genes via interaction with the TFIIH subunit p8.

In response to viral infection, the host innate antiviral response is elicited to limit viral replication. Many viruses have evolved various strategies to circumvent the host antiviral response. It has been reported that matrix (M) protein of vesicular stomatitis virus (VSV) can inhibit host gene expression to evade the host innate immune response. However, the molecular mechanism remains unclear. Here, we demonstrated that VSV M protein inhibited transcription of a reporter gene transfected into BSR-T7/5 cells. To further investigate the underlying mechanism, a yeast two-hybrid screen was performed to search for host proteins that interact with the M protein. The subunit of transcription/repair factor TFIIH, p8, was identified as an M binding partner, and the interaction was validated with a GST pull-down assay and laser confocal microscopy. Through a mutagenesis analysis, we found that the p8-M interaction was impaired when I96, E156, R159 and R160 residues on M were replaced with Ala. These mutants reduced the inhibitory effect on transcription of the reporter gene. Furthermore, the transcription inhibition mediated by M was impaired when co-expressed with p8. These results indicate that the p8-M interaction plays an important role in inhibiting transcription of host genes.