Whole genome re-sequencing reveals artificial and natural selection for milk traits in East Friesian sheep.

The East Friesian sheep is one of the important high-yielding dairy sheep breeds, but still little is known about their genetic and genomic variation during domestication. Therefore, we analyzed the genomic data of 46 sheep with the aim of identifying candidate genes that are closely related to milk production traits. Our genomic data consisted of 20 East Friesian sheep and 26 Asian Mouflon wild sheep. Finally, a total of 32590241 SNPs were identified, of which 0.61% (198277) SNPs were located in exonic regions. After further screening, 122 shared genomic regions in the top 1% of F ST and top 1% of Nucleotide diversity ratio were obtained. After genome annotation, these 122 candidate genomic regions were found to contain a total of 184 candidate genes. Finally, the results of KEGG enrichment analysis showed four significantly enriched pathways (P < 0.05): beta-Alanine metabolism (SMOX, HIBCH), Pathways in cancer (GLI2, AR, TXNRD3, TRAF3, FGF16), Non-homologous end-joining (MRE11), Epstein-Barr virus infection (TRAF3, PSMD13, SIN3A). Finally, we identified four important KEGG enrichment pathways and 10 candidate genes that are closely related to milk production in East Friesian sheep. These results provide valuable candidate genes for the study of milk production traits in East Friesian sheep and lay an important foundation for the study of milk production traits.

Surfactin Inhibits Membrane Fusion during Invasion of Epithelial Cells by Enveloped Viruses.

Because membrane fusion is a crucial step in the process by which enveloped viruses invade host cells, membrane fusion inhibitors can be effective drugs against enveloped viruses. We found that surfactin from Bacillus subtilis can suppress the proliferation of porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) in epithelial cells at a relatively low concentration range (15 to 50 µg/ml), without cytotoxicity or viral membrane disruption. Membrane fusion inhibition experiments demonstrate that surfactin treatment significantly reduces the rate at which the virus fuses to the cell membrane. Thermodynamic experiments show that the incorporation of small amounts of surfactin hinders the formation of negative curvature by lamellar-phase lipids, suggesting that surfactin acts a membrane fusion inhibitor. A fluorescent lipopeptide similar to surfactin was synthesized, and its ability to insert into the viral membrane was confirmed by spectroscopy. In vivo experiments have shown that oral administration of surfactin to piglets protects against PEDV infection. In conclusion, our study indicates that surfactin is a membrane fusion inhibitor with activity against enveloped viruses. As the first reported naturally occurring wedge lipid membrane fusion inhibitor, surfactin is likely to be a prototype for the development of a broad range of novel antiviral drugs.IMPORTANCE Membrane fusion inhibitors are a rapidly emerging class of antiviral drugs that inhibit the infection process of enveloped viruses. They can be classified, on the basis of the viral components targeted, as fusion protein targeting or membrane lipid targeting. Lipid-targeting membrane fusion inhibitors have a broader antiviral spectrum and are less likely to select for drug-resistant mutations. Here we show that surfactin is a membrane fusion inhibitor and has a strong antiviral effect. The insertion of surfactin into the viral envelope lipids reduces the probability of viral fusion. We also demonstrate that oral administration of surfactin protects piglets from PEDV infection. Surfactin is the first naturally occurring wedge lipid membrane fusion inhibitor that has been identified and may be effective against many viruses beyond the scope of this study. Understanding its mechanism of action provides a foundation for the development of novel antiviral agents.