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dc.contributor.authorShogan, Benjamin
dc.contributor.authorKruse, Lori
dc.contributor.authorMulamba, Gilbert
dc.contributor.authorAndré Hu
dc.contributor.authorCoen, Donald
dc.date.accessioned2019-10-05T03:27:35Z
dc.date.issued2006
dc.identifier.citationShogan, B., L. Kruse, G. B. Mulamba, A. Hu, and D. M. Coen. 2006. “Virucidal Activity of a GT-Rich Oligonucleotide against Herpes Simplex Virus Mediated by Glycoprotein B.” Journal of Virology 80 (10): 4740–47. https://doi.org/10.1128/jvi.80.10.4740-4747.2006.
dc.identifier.issn0022-538X
dc.identifier.issn1070-6321
dc.identifier.issn1098-5514
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41482946*
dc.description.abstractWe have investigated the antiviral mechanism of a phosphorothioate oligonucleotide, ISIS 5652, which has activity against herpes simplex virus (HSV) in the low micromolar range in plaque reduction assays. We isolated a mutant that is resistant to this compound. Marker rescue and sequencing experiments showed that resistance was due to at least one of three mutations in the UL27 gene which result in amino acid changes in glycoprotein B (gB). Because gB has a role in attachment and entry of HSV, we tested the effects of ISIS 5652 at these stages of infection. The oligonucleotide potently inhibited attachment of virus to cells at 4 degrees C; however, the resistant mutant did not exhibit resistance at this stage. Moreover, a different oligonucleotide with little activity in plaque reduction assays was as potent as ISIS 5652 in inhibiting attachment. Similarly, ISIS 5652 was able to inhibit entry of preattached virions into cells at 37 degrees C, but the mutant did not exhibit resistance in this assay. The mutant did not attach to or enter cells more quickly than did wild-type virus. Strikingly, incubation of wild-type virus with 1 to 2 mu M ISIS 5652 at 37 degrees C led to a time-dependent, irreversible loss of infectivity (virucidal activity). No virucidal activity was detected at 4 degrees C or with an unrelated oligonucleotide at 37 degrees C. The resistant mutant and a marker-rescued derivative containing its gB mutations exhibited substantial resistance to this virucidal activity of ISIS 5652. We hypothesize that the GT-rich oligonucleotide induces a conformational change in gB that results in inactivation of infectivity.
dc.language.isoen_US
dc.publisherAmerican Society for Microbiology
dash.licenseLAA
dc.titleVirucidal Activity of a GT-Rich Oligonucleotide against Herpes Simplex Virus Mediated by Glycoprotein B
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalJournal of Virology
dash.depositing.authorCoen, Donald Mark::f1d1eb8434c5ee0d3e2fa13c1a313e4d::600
dc.date.available2019-10-05T03:27:35Z
dash.workflow.comments1Science Serial ID 62982
dc.identifier.doi10.1128/JVI.80.10.4740-4747.2006
dash.source.volume80;10
dash.source.page4740


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