G (40). Coincidently, we also observed cell necrosis in the spleen of FMO fish, indicating that the cellFIGURE 8 | The schematic diagram on the causes for the age-dependent viral susceptibility in grass carp. The downward dark blue arrows indicated these representative pathways had been down-regulated in FMO fish groups, even though the upward red arrows represented these pathways had been up-regulated in TYO fish.Frontiers in Immunology | www.frontiersin.orgJune 2021 | Volume 12 | ArticleHe et al.Age-Related Viral Susceptibility in Fishmembranes were broken in FMO fish right after virus infection, resulting within the downregulation of your glycerophospholipid metabolism pathway. Nevertheless, the activation of pathways associated to membrane-structure organelles (proteasome, lysosome, and phagosome) in TYO fish indicated the formation of membranestructured organelles to remove the virus. For that reason, these final results highlight the crucial part of glycerophospholipids in host defense against viral infections.immune response right away, and the host translation machinery was hijacked by the virus for viral protein synthesis, resulting in death. However, the older, TYO fish recognized the virus quickly, quickly activated the immune response, and elevated host translation machinery involved in DNA replication, RNA transcription and translation, at the same time as biosynthesis and metabolism to defend against viruses (Figure eight).Nucleotide MetabolismThe nucleotide metabolism-related pathways (pyrimidine metabolism and purine metabolism) had been activated in TYO fish immediately after virus infection, and DEMs connected to these pathways had been primarily Adenosine A1 receptor (A1R) Agonist Biological Activity upregulated in this group. Sigma 1 Receptor Synonyms Nucleotides are central to biological signaling and also the transfer of genetic information and facts, which are important for DNA and RNA synthesis, and thus, for protein synthesis (41, 42). The upregulation of these pathways in TYO fish may well be because of them responding positively to virus infection along with the initiation of DNA replication, RNA transcription and translation, at the same time as protein synthesis, in an effort to eradicate the virus. The downregulation of these pathways in FMO fish implies that the host translation machinery is hjjacked or shut down by GCRV to facilitate the replication and spread with the virus. Similarly, the nucleotide metabolism-related pathways have been downregulated in classical swine fever virus-infected piglets (43), and purine metabolism was downregulated in bisphenol A-treated zebrafish (44, 45). Collectively, these results show the very important role of nucleotide metabolism in response to virus infection or toxicity stimulation.Data AVAILABILITY STATEMENTThe datasets presented in this study could be identified in on the net repositories. The names of the repository/repositories and accession number(s) may be located within the article/Supplementary Material.ETHICS STATEMENTThe animal study was reviewed and authorized by the committee from the Institute of Hydrobiology, Chinese Academy of Sciences.AUTHOR CONTRIBUTIONSLH, YW, and ZZ made research. LH, DZ, XL, and YL performed study. RH, CY, and LL contributed new reagents or analytic tools. LH, DZ, and XL analyzed information. LH and YW wrote the paper. All authors contributed towards the short article and authorized the submitted version.Arachidonic Acid MetabolismWe located that the arachidonic acid metabolism pathway was also drastically upregulated in TYO fish just after virus infection. Arachidonic acid can be a polyunsaturated omega-6 fatty acid plus a precursor within the biosynthesis of prostaglandins,.