PMID- 28613152 OWN - NLM STAT- MEDLINE DCOM- 20170717 LR - 20211204 IS - 1465-2099 (Electronic) IS - 0022-1317 (Print) IS - 0022-1317 (Linking) VI - 98 IP - 6 DP - 2017 Jun TI - Reduction of infection by inhibiting mTOR pathway is associated with reversed repression of type I interferon by porcine reproductive and respiratory syndrome virus. PG - 1316-1328 LID - 10.1099/jgv.0.000802 [doi] AB - Type I interferons (IFNs) are critical in animal antiviral regulation. IFN-mediated signalling regulates hundreds of genes that are directly associated with antiviral, immune and other physiological responses. The signalling pathway mediated by mechanistic target of rapamycin (mTOR), a serine/threonine kinase regulated by IFNs, is key in regulation of cellular metabolism and was recently implicated in host antiviral responses. However, little is known about how animal type I IFN signalling coordinates immunometabolic reactions during antiviral defence. Here, using porcine reproductive and respiratory syndrome virus (PRRSV), we found that the genes in the mTOR signalling pathway were differently regulated in PRRSV-infected porcine alveolar macrophages at different activation statuses. Moreover, mTOR signalling regulated PRRSV infection in MARC-145 and primary porcine cells, in part, through modulating the production and signalling of type I IFNs. Taken together, we determined that the mTOR signalling pathway involves PRRSV infection and regulates expression and signalling of type I IFNs against viral infection. These findings suggest that the mTOR signalling pathway has a bi-directional loop with the type I IFN system and imply that some components in the mTOR signalling pathway can be utilized as targets for studying antiviral immunity and for designing therapeutic reagents. FAU - Liu, Qinfang AU - Liu Q AD - Departments of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA. FAU - Miller, Laura C AU - Miller LC AD - USDA, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, 1920 Dayton Avenue, Ames, IA 50010, USA. FAU - Blecha, Frank AU - Blecha F AD - Departments of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA. FAU - Sang, Yongming AU - Sang Y AD - Present address: Department of Agricultural and Environmental Sciences, College of Agriculture, Human and Natural Sciences, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN, USA. AD - Departments of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA. LA - eng GR - P20 RR017686/RR/NCRR NIH HHS/United States PT - Journal Article DEP - 20170614 PL - England TA - J Gen Virol JT - The Journal of general virology JID - 0077340 RN - 0 (Interferon Type I) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Cells, Cultured MH - Epithelial Cells/immunology/virology MH - *Host-Pathogen Interactions MH - Interferon Type I/*metabolism MH - Macrophages, Alveolar/immunology/virology MH - Porcine respiratory and reproductive syndrome virus/*physiology MH - Signal Transduction MH - Swine MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors PMC - PMC5962895 COIS- The authors declare that there are no conflicts of interest. EDAT- 2017/06/15 06:00 MHDA- 2017/07/18 06:00 PMCR- 2017/06/14 CRDT- 2017/06/15 06:00 PHST- 2017/06/15 06:00 [pubmed] PHST- 2017/07/18 06:00 [medline] PHST- 2017/06/15 06:00 [entrez] PHST- 2017/06/14 00:00 [pmc-release] AID - 000802 [pii] AID - 10.1099/jgv.0.000802 [doi] PST - ppublish SO - J Gen Virol. 2017 Jun;98(6):1316-1328. doi: 10.1099/jgv.0.000802. Epub 2017 Jun 14.