{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:03:00Z","timestamp":1790913780886,"version":"4.1.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"6","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["1ZIABC011176"],"award-info":[{"award-number":["1ZIABC011176"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,2,7]]},"abstract":"<jats:p>\n                    Non-coding RNAs (ncRNAs) play important roles in host-pathogen interactions; oncogenic viruses like Kaposi\u2019s sarcoma herpesvirus (KSHV) employ ncRNAs to establish a latent reservoir and persist for the life of the host. We previously reported that KSHV infection alters a novel class of RNA, circular RNAs (circRNAs). CircRNAs are alternative splicing isoforms and regulate gene expression, but their importance in infection is largely unknown. Here, we showed that a human circRNA, hsa_circ_0001400, is induced by various pathogenic viruses, namely KSHV, Epstein-Barr virus, and human cytomegalovirus. The induction of circRNAs including circ_0001400 by KSHV is co-transcriptionally regulated, likely at splicing. Consistently, screening for circ_0001400-interacting proteins identified a splicing factor, PNISR. Functional studies using infected primary endothelial cells revealed that circ_0001400 inhibits KSHV lytic transcription and virus production. Simultaneously, the circRNA promoted cell cycle, inhibited apoptosis, and induced immune genes. RNA-pull down assays identified transcripts interacting with circ_0001400, including\n                    <jats:italic>TTI1<\/jats:italic>\n                    , which is a component of the pro-growth mTOR complexes. We thus identified a circRNA that is pro-growth and anti-lytic replication. These results support a model in which KSHV induces circ_0001400 expression to maintain latency. Since circ_0001400 is induced by multiple viruses, this novel viral strategy may be widely employed by other viruses.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2212864120","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T14:01:56Z","timestamp":1675260116000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":47,"title":["A virus-induced circular RNA maintains latent infection of Kaposi\u2019s sarcoma herpesvirus"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8637-2996","authenticated-orcid":false,"given":"Takanobu","family":"Tagawa","sequence":"first","affiliation":[{"name":"HIV and AIDS Malignancy Branch, Center of Cancer Research, National Cancer Institute, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8911-7154","authenticated-orcid":false,"given":"Daniel","family":"Oh","sequence":"additional","affiliation":[{"name":"HIV and AIDS Malignancy Branch, Center of Cancer Research, National Cancer Institute, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0968-3090","authenticated-orcid":false,"given":"Sarah","family":"Dremel","sequence":"additional","affiliation":[{"name":"HIV and AIDS Malignancy Branch, Center of Cancer Research, National Cancer Institute, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0728-4566","authenticated-orcid":false,"given":"Guruswamy","family":"Mahesh","sequence":"additional","affiliation":[{"name":"HIV and AIDS Malignancy Branch, Center of Cancer Research, National Cancer Institute, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8978-8495","authenticated-orcid":false,"given":"Vishal N.","family":"Koparde","sequence":"additional","affiliation":[{"name":"Center for Cancer Research Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892"},{"name":"Advanced Biomedical Computational Sciences, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21701"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Duncan","sequence":"additional","affiliation":[{"name":"Protein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21701"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9545-2450","authenticated-orcid":false,"given":"Thorkell","family":"Andresson","sequence":"additional","affiliation":[{"name":"Protein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21701"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6464-6941","authenticated-orcid":false,"given":"Joseph M.","family":"Ziegelbauer","sequence":"additional","affiliation":[{"name":"HIV and AIDS Malignancy Branch, Center of Cancer Research, National Cancer Institute, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,2]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00124-13"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00713"},{"key":"e_1_3_4_3_2","first-page":"1","article-title":"Unraveling the mysterious interactions between Hepatitis C virus RNA and liver-specific MicroRNA-122","volume":"3","author":"Sarnow P.","year":"2015","unstructured":"P. Sarnow, S. M. Sagan, Unraveling the mysterious interactions between Hepatitis C virus RNA and liver-specific MicroRNA-122. Ann. Rev. Virol. 3, 1\u201324 (2015).","journal-title":"Ann. Rev. Virol."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/v6114212"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02380-07"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01804-07"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00752-08"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0158-7"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11928"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11993"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816183115"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.670542"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811728115"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01952-18"},{"key":"e_1_3_4_15_2","article-title":"Kaposi's sarcoma herpesvirus induces host circular RNAs and maintain latent infection","author":"Ziegelbauer J.","unstructured":"J. Ziegelbauer, Kaposi's sarcoma herpesvirus induces host circular RNAs and maintain latent infection. Gene Expression Omnibus. https:\/\/0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk\/geo\/query\/acc.cgi?acc=GSE206930. Deposited 25 June 2022.","journal-title":"Gene Expression Omnibus"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710799114"},{"key":"e_1_3_4_17_2","article-title":"Total RNA-Seq in HSV-1 infected human fibroblasts","author":"Dremel S.","unstructured":"S. Dremel, Total RNA-Seq in HSV-1 infected human fibroblasts. Sequence Read Archive. https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA851702\/. Deposited 27 July 2022.","journal-title":"Sequence Read Archive"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2019.11.004"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02907-21"},{"key":"e_1_3_4_20_2","unstructured":"S. Dremel 4SU-Seq of KSHV lytic reactivation in iSLK-BAC16 model. 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