{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T18:05:16Z","timestamp":1785175516299,"version":"3.55.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["CA019014, CA291437, and CA163217"],"award-info":[{"award-number":["CA019014, CA291437, and CA163217"]}]},{"name":"NIH","award":["T32 AI007001"],"award-info":[{"award-number":["T32 AI007001"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus that is associated with several human malignancies, and primary infection by KSHV can activate both DNA and RNA sensing pathways. Host innate immunity is a rapid, first-line defense against foreign pathogens, where pattern recognition receptors detect virus-associated antigens and activate the type I interferon response to prime the cell to an antiviral state to limit viral infections. However, viruses such as gammaherpesviruses, have evolved mechanisms to co-opt host factors to antagonize these pathways to promote persistent infection. The cellular vaccinia-related kinase (VRK) family is a trio of serine\/threonine kinases, VRK1, VRK2 and VRK3, named for their homology to the vaccinia virus B1 kinase. The VRKs are involved in many cellular processes, including nuclear envelope assembly during mitosis and the DNA damage response. However, the role of the VRKs in KSHV infection and innate immunity has not previously been explored. We found that VRK3 is upregulated in response to KSHV primary infection of endothelial cells. VRK3 is also upregulated during KSHV reactivation from latency. Knockdown of VRK3 limited KSHV primary infection and lytic reactivation and resulted in increased activation of TBK1 and IRF3 and subsequent upregulation of interferon stimulated genes. Overexpression of VRK3 reversed this phenotype. Furthermore, we are also the first to demonstrate that VRK3 is a negative regulator of the interferon response even in the absence of viral infection. Collectively, our data highlight the importance of the host factor, VRK3, as a novel suppressor of the type I interferon response during the KSHV viral lifecycle.<\/jats:p>","DOI":"10.1371\/journal.ppat.1014400","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T17:43:09Z","timestamp":1785174189000},"page":"e1014400","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["VRK3 promotes KSHV infection by suppressing the antiviral type I interferon response"],"prefix":"10.1371","volume":"22","author":[{"given":"Caroline J.","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9205-1774","authenticated-orcid":true,"given":"Blossom","family":"Damania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"issue":"21","key":"ppat.1014400.ref001","article-title":"Molecular mechanisms of Kaposi sarcoma-associated herpesvirus (HHV8)-related lymphomagenesis","volume":"16","author":"CJ Yu","year":"2024","journal-title":"Cancers"},{"issue":"2","key":"ppat.1014400.ref002","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3390\/v17020177","article-title":"Unraveling the Kaposi Sarcoma-Associated Herpesvirus (KSHV) lifecycle: An overview of latency, lytic replication, and KSHV-associated diseases","volume":"17","author":"VA Losay","year":"2025","journal-title":"Viruses"},{"key":"ppat.1014400.ref003","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511545313.031","article-title":"KSHV manipulation of the cell cycle and apoptosis","volume-title":"Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis","author":"PS. 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