Peste des petits ruminants virus (PPRV) causes highly contagious diseases in domestic and particular wild small ruminants, leading to substantial economic loss. The development of effective and cheap antiviral medications shall help to circumvent this emerging burden. In this study, we found that ribavirin, a competitive inosine-5’-monophosphate dehydrogenase (IMPDH) inhibitor, significantly inhibits the replication of PPRV. As IMPDH is a key enzyme in purine nucleotide synthesis, supplementation of exogenous guanosine attenuate the anti-PPRV effect of ribavirin. Interestingly, an uncompetitive IMPDH inhibitor, mycophenolic acid (MPA), exerted more potent antiviral effect again PPRV. Similarly, this effect was largely restored upon supplementation of guanosine. Thus, we have demonstrated that the IMPDH inhibitors ribavirin and MPA combat PPRV infection through purine nucleotide depletion. Because both regimens have been widely used in the clinic for treating viral infection or organ rejection in transplantation patients for decades, respectively, repurposing these existing safe and cheap medications may provide a new avenue for combating PPRV infection. 相似文献
1. There has been substantial research focused on the roles of microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs) derived from mammalian spermatozoa; however, comparatively little is known about the role of spermatozoa-derived miRNAs and piRNAs within breeding cockerels’ spermatozoa.
2. A small RNA library of cockerels’ spermatozoa was constructed using Illumina high-throughput sequencing technology. Unique sequences with lengths of 18–26 nucleotides were mapped to miRBase 21.0 and unique sequences with lengths of 25–37 nucleotides were mapped to a piRNA database. A total of 1311 miRNAs and 2448 potential piRNAs were identified. Based on stem-loop qRT-PCR, 8 miRNAs were validated.
3. Potential target genes of the abundant miRNAs were predicted, and further Kyoto Encyclopedia of Genes and Genomes database (KEGG) and Gene Ontology (GO) analyses were performed, which revealed that some candidate miRNAs were involved in the spermatogenesis process, spermatozoa epigenetic programming and further embryonic development.
5. GO and KEGG analyses based on mapping genes of expressed piRNAs were performed, which revealed that spermatozoal piRNAs could play important regulatory roles in embryonic development of offspring.
6. The search for endogenous spermatozoa miRNAs and piRNAs will contribute to a preliminary database for functional and molecular mechanistic studies in embryonic development and spermatozoa epigenetic programming. 相似文献
Liver metabolism is affected by nutrients. The aim of this study was to explore the effects of low‐protein diets (17% crude protein, CP) supplemented with branched‐chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile) and valine (Val), on hepatic amino acid profile and lipid metabolism in growing pigs. The ratio of Leu : Ile : Val in all groups was 1 : 0.51 : 0.63 (20% crude protein, CP), 1 : 1 : 1 (17% CP), 1 : 0.75 : 0.75 (17% CP), 1 : 0.51 : 0.63 (17% CP) and 1 : 0.25 : 0.25 (17% CP) respectively. Results revealed that compared to the positive control group (1 : 0.51 : 0.63, 20% CP), the low‐protein diets significantly augmented the concentrations of most essential amino acids and non‐essential amino acids (p <.05), with the greatest values observed in the 1 : 0.25 : 0.25 group. Moreover, relative to the control, the low‐protein diets with the Leu : Ile : Val ratio ranging from 1 : 0.75 : 0.75 to 1 : 0.25 : 0.25 markedly downregulated the mRNA abundance of acetyl‐CoA carboxylase (ACC), lipoprotein lipase (LPL) and fatty acid‐binding protein 4 (FABP‐4) (p <.05), and upregulated the mRNA expression of hormone‐sensitive lipase (HSL), peroxisome proliferator‐activated receptor‐g coactivator‐1α (PGC‐1α), uncoupling protein 3 (UCP3) and liver carnitine palmitoyltransferase 1 (L‐CPT‐1) (p <.05). Therefore, our data suggest that protein‐restricted diets supplemented with optimal BCAA ratio, that is, 1 : 0.75 : 0.75–1 : 0.25 : 0.25, induce a shift from fatty acid synthesis to fatty acid oxidation in the liver of growing pigs. These effects may be associated with increased mitochondrial biogenesis. 相似文献