{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:55:41Z","timestamp":1784681741623,"version":"3.55.0"},"reference-count":96,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,14]],"date-time":"2024-12-14T00:00:00Z","timestamp":1734134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R56 AI137264"],"award-info":[{"award-number":["R56 AI137264"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Chikungunya virus (CHIKV) is an emerging, mosquito-borne arthritic alphavirus increasingly associated with severe neurological sequelae and long-term morbidity. However, there is limited understanding of the crucial host components involved in CHIKV replicase assembly complex formation, and thus virus replication and virulence-determining factors, within the central nervous system (CNS). Furthermore, the majority of CHIKV CNS studies focus on neuronal infection, even though astrocytes represent the main cerebral target. Heterogeneous ribonucleoprotein K (hnRNP K), an RNA-binding protein involved in RNA splicing, trafficking, and translation, is a regulatory component of alphavirus replicase assembly complexes, but has yet to be thoroughly studied in the context of CHIKV infection. We identified the hnRNP K CHIKV viral RNA (vRNA) binding site via sequence alignment and performed site-directed mutagenesis to generate a mutant, \u0394hnRNPK-BS1, with disrupted hnRNPK\u2013vRNA binding, as verified through RNA coimmunoprecipitation and RT-qPCR. CHIKV \u0394hnRNPK-BS1 demonstrated hampered replication in both NSC-34 neuronal and C8-D1A astrocytic cultures. In astrocytes, disruption of the hnRNPK\u2013vRNA interaction curtailed viral RNA transcription and shut down subgenomic RNA translation. Our study demonstrates that hnRNP K serves as a crucial RNA-binding host factor that regulates CHIKV replication through the modulation of subgenomic RNA translation.<\/jats:p>","DOI":"10.3390\/v16121918","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T06:48:39Z","timestamp":1734331719000},"page":"1918","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Heterogeneous Ribonucleoprotein K Is a Host Regulatory Factor of Chikungunya Virus Replication in Astrocytes"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7750-8983","authenticated-orcid":false,"given":"Lisa","family":"Pieterse","sequence":"first","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8456-9567","authenticated-orcid":false,"given":"Maranda","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3180-2447","authenticated-orcid":false,"given":"Rachy","family":"Abraham","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane E.","family":"Griffin","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Barr, K.L., and Vaidhyanathan, V. (2019). Chikungunya in Infants and Children: Is Pathogenesis Increasing?. Viruses, 11.","DOI":"10.3390\/v11030294"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1093\/cid\/ciy1083","article-title":"Concomitant Transmission of Dengue, Chikungunya, and Zika Viruses in Brazil: Clinical and Epidemiological Findings From Surveillance for Acute Febrile Illness","volume":"69","author":"Silva","year":"2019","journal-title":"Clin. Infect. 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