Effect of the Viral Hemorrhagic Septicemia Virus Nonvirion Protein on Translation via PERK-eIF2α Pathway
| dc.contributor.author | Kesterson, Shelby Powell | |
| dc.contributor.author | Ringiesn, Jeffery | |
| dc.contributor.author | Vakharia, Vikram N. | |
| dc.contributor.author | Shepherd, Brian S. | |
| dc.contributor.author | Leaman, Douglas W. | |
| dc.contributor.author | Malathi, Krishnamurthy | |
| dc.date.accessioned | 2020-06-11T16:31:38Z | |
| dc.date.available | 2020-06-11T16:31:38Z | |
| dc.date.issued | 2020-04-30 | |
| dc.description.abstract | Viral hemorrhagic septicemia virus (VHSV) is one of the most deadly infectious fish pathogens, posing a serious threat to the aquaculture industry and freshwater ecosystems worldwide. Previous work showed that VHSV sub-genotype IVb suppresses host innate immune responses, but the exact mechanism by which VHSV IVb inhibits antiviral response remains incompletely characterized. As with other novirhabdoviruses, VHSV IVb contains a unique and highly variable nonvirion (NV) gene, which is implicated in viral replication, virus-induced apoptosis and regulating interferon (IFN) production. However, the molecular mechanisms underlying the role of IVb NV gene in regulating viral or cellular processes is poorly understood. Compared to the wild-type recombinant (rWT) VHSV, mutant VHSV lacking a functional IVb NV reduced IFN expression and compromised innate immune response of the host cells by inhibiting translation. VHSV IVb infection increased phosphorylated eukaryotic initiation factor 2α (p-eIF2α), resulting in host translation shutoff. However, VHSV IVb protein synthesis proceeds despite increasing phosphorylation of eIF2α. During VHSV IVb infection, eIF2α phosphorylation was mediated via PKR-like endoplasmic reticulum kinase (PERK) and was required for efficient viral protein synthesis, but shutoff of host translation and IFN signaling was independent of p-eIF2α. Similarly, IVb NV null VHSV infection induced less p-eIF2α, but exhibited decreased viral protein synthesis despite increased levels of viral mRNA. These findings show a role for IVb NV in VHSV pathogenesis by utilizing the PERK-eIF2α pathway for viral-mediated host shutoff and interferon signaling to regulate host cell response. | en_US |
| dc.description.sponsorship | This work was supported by National Institutes of Health (NIH) Grants AI119980-01A1 (K.M.), startup funds from University of Toledo (K.M), NSF grant DBI-1354806/1354684 (D.W.L., V.N.V.) and USDA/ARS CRIS project numbers 5090-31320-004-00D and 5090-31320-005-00D under cooperative agreement number 58-5090-6-057 (K.M., D.W.L., B.S.S.). The views contained in this document are those of the authors and should not be interpreted as necessarily representing the o cial policies, either expressed or implied, of the U.S. Government. Mention of trade name, proprietary product, or specific equipment does not constitute a guarantee or warranty by the USDA and does not imply its approval to the exclusion of other products that may be suitable. The USDA is an Equal Opportunity Employer. We thank Scott Leisner, Saurabh Chattopadhyay and Travis Taylor (University of Toledo) for valuable discussions through the course of this work. We also thank Praveen Manivannan and Barkha Ramnani for technical assistance with some of the experiments. | en_US |
| dc.description.uri | https://www.mdpi.com/1999-4915/12/5/499 | en_US |
| dc.format.extent | 18 pages | en_US |
| dc.genre | journal articles | en_US |
| dc.identifier | doi:10.13016/m2puch-lwvc | |
| dc.identifier.citation | Kesterson, Shelby P.; Ringiesn, Jeffery; Vakharia, Vikram N.; Shepherd, Brian S.; Leaman, Douglas W.; Malathi, Krishnamurthy. 2020. "Effect of the Viral Hemorrhagic Septicemia Virus Nonvirion Protein on Translation via PERK-eIF2α Pathway." Viruses 12, no. 5: 499, https://doi.org/10.3390/v12050499 | en_US |
| dc.identifier.uri | https://doi.org/10.3390/v12050499 | |
| dc.identifier.uri | http://hdl.handle.net/11603/18869 | |
| dc.language.iso | en_US | en_US |
| dc.publisher | MDPI | en_US |
| dc.relation.isAvailableAt | The University of Maryland, Baltimore County (UMBC) | |
| dc.relation.ispartof | UMBC Department of Marine Biotechnology | |
| dc.relation.ispartof | UMBC Student Collection | |
| dc.relation.ispartof | UMBC Faculty Collection | |
| dc.rights | This item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author. | |
| dc.rights | Attribution 4.0 International | * |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | * |
| dc.title | Effect of the Viral Hemorrhagic Septicemia Virus Nonvirion Protein on Translation via PERK-eIF2α Pathway | en_US |
| dc.type | Text | en_US |