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The duck Tembusu virus (DTMUV) is a mosquito-borne flavivirus. It causes severe symptoms of egg-drop, as well as neurological symptoms and brain damage in ducks. However, the specific molecular mechanisms of DTMUV-induced neurovirulence and host responses in the brain remain obscure. To better understand the host&ndash, pathogen and neuro-immune interactions of DTMUV infection, we conducted high-throughput RNA-sequencing to reveal the transcriptome profiles of DTMUV-infected duck brain. Totals of 117, 212, and 150 differentially expressed genes (DEGs) were identified at 12, 24, and 48 h post infection (hpi). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses uncovered genes and pathways related to the nervous system and immune responses in duck brain. Neuro-related genes, including WNT3A, GATA3, and CHRNA6, were found to be significantly downregulated. RIG-I-like receptors (DHX58, IFIH1) and Toll-like receptors (TLR2 and TLR3) were activated, inducing the expression of 22 interferon stimulated genes (ISGs) and antigen-processing and -presenting genes (TAP1 and TAP2) in the brain. Our research provides comprehensive information for the molecular mechanisms of neuro-immune and host&ndash, pathogen interactions of DTMUV.

Highlights • Firstly generated a NDV-vectored Duck Tembusu Virus (DTMUV) bivalent vaccine that expressing the pre-membrane and envelope proteins of DTMUV. • Evaluated the efficacy of the NDV-vectored Duck Tembusu Virus bivalent vaccine. • Provided a new method for NDV and DTMUV controlling in waterfowl., The newly emerged Duck Tembusu virus (DTMUV) is responsible for considerable economic loss in waterfowl-raising areas in China since 2010. Meanwhile, the virulent Newcastle disease virus (NDV) has also caused sporadic outbreaks in waterfowl. The individual vaccines against both diseases are available, however, there is no bivalent or combined vaccine for either disease. Here, we constructed a recombinant NDV-vectored vaccine candidate that expresses the pre-membrane (prM) and envelope (E) genes from DTMUV, designated as aGM/prM + E. The foreign prM and E proteins were stably expressed in aGM/prM + E and exhibited similar pathogenicity but higher growth kinetics than those of the parental virus. The aGM/prM + E carries a fusion cleavage site in accordance with avirulent viruses that have been frequently isolated from waterfowl, and induced remarkably (p

A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. Therefore, we aimed to establish whether rs641738 is a risk factor for NAFLD through meta-analysis. Data from 134,015 participants (7,692 with liver biopsies and 50,680 with imaging) was included in the meta-analysis. The minor T-allele of rs641738C>T was associated with higher liver fat on CT/MRI using an additive genetic model (+0.05 standard deviations [95% CI: 0.01 - 0.09], p=0.025), and with an increased risk of NAFLD (per-allele OR: 1.08 [95% CI: 1.01 - 1.15]), nonalcoholic steatohepatitis (OR: 1.11 [95% CI: 1.02 - 1.21]), advanced fibrosis (OR: 1.14 [95% CI: 1.05 - 1.23]), and hepatocellular carcinoma (OR: 1.43 [95% CI: 1.22 - 1.67]) in adults with NAFLD. Sub-group analysis did not demonstrate a difference in Caucasians and non-Caucasians. Rs641738C>T was not associated with markers of insulin resistance but was associated with higher risk of stroke in the UK Biobank. These data validate rs641738C>T near MBOAT7 as a risk factor for the development, activity, and stage of NAFLD including hepatocellular carcinoma.

A new family of IFNs called type III IFN or IFN-λ has been described, and shown to induce antiviral activity against several viruses in the cell culture. In this study, the molecular cloning, expression, and antiporcine epidemic diarrhea virus (PEDV) activity of porcine IFN-λ3 (poIFN-λ3) were reported. The full-length poIFN-λ3 cDNA sequence encoded 196 amino acids with a 23 amino acid signal peptide. Sequence alignments showed that poIFN-λ3 had an amino acid sequence similarity to Ovis aries (78.1 %), Bos taurus (76.0 %), Tupaia belangeri (71.3 %), Equus caballus (69.9 %), and Homo sapiens (69.9 %). The phylogenetic analysis based on the genomic sequences indicated that poIFN-λ3 is located in the same branch as B. taurus and O. aries IFN-λ3. The poIFN-λ3 without a signal anchor sequence was efficiently expressed in Escherichia coli, and the purified recombinant poIFN-λ3 exhibited significant antiviral effects against PEDV in a dose- and time-dependent manner. This inhibitory effect of poIFN-λ3 on PEDV was observed under three different treatment conditions. The highest inhibition of PEDV was observed in Vero E6 cell cultures pretreated with poIFN-λ3 (prior to PEDV infection). In addition, poIFN-λ3 was able to induce the expression of IFN-stimulated genes, including ISG15, OAS1, and Mx1 in Vero E6 cells. These data demonstrate that poIFN-λ3 has antiviral activity against PEDV and may serve as a useful biotherapeutic candidate to inhibit PEDV or other viruses in swine.

Goose/GD/2010 is a newly emerging Newcastle disease virus (NDV) isolated from a sick goose flock in southern China. Here, we report the complete genome sequence of this isolate, which belongs to NDV subgenotype VIIb. This is the first report about the complete genome information of an isolate of subgenotype VIIb in China.