PERK Is Critical for Alphavirus Nonstructural Protein Translation

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dc.contributor.authorDahal, Bibhaen
dc.contributor.authorLehman, Caitlin W.en
dc.contributor.authorAkhrymuk, Ivan V.en
dc.contributor.authorBracci, Nicole R.en
dc.contributor.authorPanny, Laurenen
dc.contributor.authorBarrera, Michael D.en
dc.contributor.authorBhalla, Nishanken
dc.contributor.authorJacobs, Jonathan L.en
dc.contributor.authorDinman, Jonathan D.en
dc.contributor.authorKehn-Hall, Kyleneen
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.date.accessioned2021-05-14T13:16:01Zen
dc.date.available2021-05-14T13:16:01Zen
dc.date.issued2021-05-12en
dc.date.updated2021-05-13T14:35:57Zen
dc.description.abstractVenezuelan equine encephalitis virus (VEEV) is an alphavirus that causes encephalitis. Previous work indicated that VEEV infection induced early growth response 1 (EGR1) expression, leading to cell death via the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) arm of the unfolded protein response (UPR) pathway. Loss of PERK prevented EGR1 induction and decreased VEEV-induced death. The results presented within show that loss of PERK in human primary astrocytes dramatically reduced VEEV and eastern equine encephalitis virus (EEEV) infectious titers by 4–5 log<sub>10</sub>. Loss of PERK also suppressed VEEV replication in primary human pericytes and human umbilical vein endothelial cells, but it had no impact on VEEV replication in transformed U87MG and 293T cells. A significant reduction in VEEV RNA levels was observed as early as 3 h post-infection, but viral entry assays indicated that the loss of PERK minimally impacted VEEV entry. In contrast, the loss of PERK resulted in a dramatic reduction in viral nonstructural protein translation and negative-strand viral RNA production. The loss of PERK also reduced the production of Rift Valley fever virus and Zika virus infectious titers. These data indicate that PERK is an essential factor for the translation of alphavirus nonstructural proteins and impacts multiple RNA viruses, making it an exciting target for antiviral development.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDahal, B.; Lehman, C.W.; Akhrymuk, I.; Bracci, N.R.; Panny, L.; Barrera, M.D.; Bhalla, N.; Jacobs, J.L.; Dinman, J.D.; Kehn-Hall, K. PERK Is Critical for Alphavirus Nonstructural Protein Translation. Viruses 2021, 13, 892.en
dc.identifier.doihttps://doi.org/10.3390/v13050892en
dc.identifier.urihttp://hdl.handle.net/10919/103296en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectVenezuelan equine encephalitis virus (VEEV)en
dc.subjecteastern equine encephalitis virus (EEEV)en
dc.subjectPERKen
dc.subjectalphavirusen
dc.subjecttranslationen
dc.titlePERK Is Critical for Alphavirus Nonstructural Protein Translationen
dc.title.serialVirusesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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