Human cytomegalovirus specifically controls the levels of the endoplasmic reticulum chaperone BiP/GRP78, which is required for virion assembly

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dc.contributor.authorBuchkovich, N.
dc.contributor.authorMaguire, T.
dc.contributor.authorYu, Y.
dc.contributor.authorPaton, A.
dc.contributor.authorPaton, J.
dc.contributor.authorAlwine, J.
dc.date.issued2008
dc.description.abstractThe endoplasmic reticulum (ER) chaperone BiP/GRP78 regulates ER function and the unfolded protein response (UPR). Human cytomegalovirus infection of human fibroblasts induces the UPR but modifies it to benefit viral replication. BiP/GRP78 protein levels are tightly regulated during infection, rising after 36 h postinfection (hpi), peaking at 60 hpi, and decreasing thereafter. To determine the effects of this regulation on viral replication, BiP/GRP78 was depleted using the SubAB subtilase cytotoxin, which rapidly and specifically cleaves BiP/GRP78. Toxin treatment of infected cells for 12-h periods beginning at 36, 48, 60, and 84 hpi caused complete loss of BiP but had little effect on viral protein synthesis. However, progeny virion formation was significantly inhibited, suggesting that BiP/GRP78 is important for virion formation. Electron microscopic analysis showed that infected cells were resistant to the toxin and showed none of the cytotoxic effects seen in uninfected cells. However, all viral activity in the cytoplasm ceased, with nucleocapsids remaining in the nucleus or concentrated in the cytoplasmic space just outside of the outer nuclear membrane. These data suggest that one effect of the controlled expression of BiP/GRP78 in infected cells is to aid in cytoplasmic virion assembly and egress.
dc.description.statementofresponsibilityNicholas J. Buchkovich, Tobi G. Maguire, Yongjun Yu, Adrienne W. Paton, James C. Paton, and James C. Alwine
dc.identifier.citationJournal of Virology, 2008; 82(1):31-39
dc.identifier.doi10.1128/JVI.01881-07
dc.identifier.issn0022-538X
dc.identifier.issn1098-5514
dc.identifier.orcidPaton, J. [0000-0001-9807-5278]
dc.identifier.urihttp://hdl.handle.net/2440/52085
dc.language.isoen
dc.publisherAmer Soc Microbiology
dc.source.urihttps://doi.org/10.1128/jvi.01881-07
dc.subjectCells, Cultured
dc.subjectNuclear Envelope
dc.subjectCell Nucleus
dc.subjectCytoplasm
dc.subjectEndoplasmic Reticulum
dc.subjectHumans
dc.subjectCytomegalovirus
dc.subjectNucleocapsid
dc.subjectHeat-Shock Proteins
dc.subjectMolecular Chaperones
dc.subjectMicroscopy, Electron, Transmission
dc.subjectVirus Assembly
dc.subjectEndoplasmic Reticulum Chaperone BiP
dc.titleHuman cytomegalovirus specifically controls the levels of the endoplasmic reticulum chaperone BiP/GRP78, which is required for virion assembly
dc.typeJournal article
pubs.publication-statusPublished

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