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- W3201520141 abstract "The Open Reading Frame 45 (ORF45) of Kaposi sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus-specific, immediate-early, tegument protein required for efficient viral replication and virion production. We have previously shown that ORF45 interacts with the conserved herpesviral protein ORF33 through the highly conserved C-terminal 19 amino acids (C19) of ORF45. Because the deletion of C19 abolished ORF33 accumulation and viral production, we reasoned that this interaction could be critical for viral production and explored as an antiviral target for gammaherpesviruses. In work described in this article, we characterize this interaction in further detail, first by revealing that this interaction is conserved among gammaherpesviruses, then by identifying residues in C19 critical for its interaction with and stabilization of ORF33. More importantly, we show that disruption of the interaction, either by mutating key residues (W403A or W405A) in C19 or by using competing cell penetration peptide TAT-C19, dramatically reduce the yield of KSHV progeny viruses. Our results not only reveal critical roles of this interaction to viral production but also provide a proof of concept for targeting the ORF33-ORF45 interaction as a novel antiviral strategy against KSHV and other gammaherpesviruses." @default.
- W3201520141 created "2021-09-27" @default.
- W3201520141 creator A5013495602 @default.
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- W3201520141 date "2021-09-14" @default.
- W3201520141 modified "2023-10-03" @default.
- W3201520141 title "Disruption of the Interaction between ORF33 and the Conserved Carboxyl-Terminus of ORF45 Abolishes Progeny Virion Production of Kaposi Sarcoma-Associated Herpesvirus" @default.
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- W3201520141 doi "https://doi.org/10.3390/v13091828" @default.
- W3201520141 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8472245" @default.
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- W3201520141 hasPublicationYear "2021" @default.
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