{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T04:56:49Z","timestamp":1773637009564,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DE016680, R01DE026101"],"award-info":[{"award-number":["R01DE016680, R01DE026101"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/v13091828","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T23:34:11Z","timestamp":1631662451000},"page":"1828","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Disruption of the Interaction between ORF33 and the Conserved Carboxyl-Terminus of ORF45 Abolishes Progeny Virion Production of Kaposi Sarcoma-Associated Herpesvirus"],"prefix":"10.3390","volume":"13","author":[{"given":"Joseph","family":"Gillen","sequence":"first","affiliation":[{"name":"Functional Cellular Networks Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4189-7008","authenticated-orcid":false,"given":"Fanxiu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Florida State University, Tallahassee, FL 32306-4370, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1126\/science.7997879","article-title":"Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi\u2019s sarcoma","volume":"266","author":"Chang","year":"1994","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1056\/NEJM199505043321802","article-title":"Kaposi\u2019s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas","volume":"332","author":"Cesarman","year":"1995","journal-title":"N. 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