{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:57:14Z","timestamp":1791457034616,"version":"4.3.4"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000180","name":"Department of Homeland Security Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD)","doi-asserted-by":"publisher","award":["2010-ST061-AG0001"],"award-info":[{"award-number":["2010-ST061-AG0001"]}],"id":[{"id":"10.13039\/100000180","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000180","name":"Department of Homeland Security Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD)","doi-asserted-by":"publisher","award":["P20GM130448"],"award-info":[{"award-number":["P20GM130448"]}],"id":[{"id":"10.13039\/100000180","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000180","name":"Department of Homeland Security Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD)","doi-asserted-by":"publisher","award":["2018-05766"],"award-info":[{"award-number":["2018-05766"]}],"id":[{"id":"10.13039\/100000180","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NBAF Transition Funds","award":["2010-ST061-AG0001"],"award-info":[{"award-number":["2010-ST061-AG0001"]}]},{"name":"NBAF Transition Funds","award":["P20GM130448"],"award-info":[{"award-number":["P20GM130448"]}]},{"name":"NBAF Transition Funds","award":["2018-05766"],"award-info":[{"award-number":["2018-05766"]}]},{"name":"National Institute of General Medical Sciences (NIGMS)","award":["2010-ST061-AG0001"],"award-info":[{"award-number":["2010-ST061-AG0001"]}]},{"name":"National Institute of General Medical Sciences (NIGMS)","award":["P20GM130448"],"award-info":[{"award-number":["P20GM130448"]}]},{"name":"National Institute of General Medical Sciences (NIGMS)","award":["2018-05766"],"award-info":[{"award-number":["2018-05766"]}]},{"name":"Swedish Research Council","award":["2010-ST061-AG0001"],"award-info":[{"award-number":["2010-ST061-AG0001"]}]},{"name":"Swedish Research Council","award":["P20GM130448"],"award-info":[{"award-number":["P20GM130448"]}]},{"name":"Swedish Research Council","award":["2018-05766"],"award-info":[{"award-number":["2018-05766"]}]},{"name":"USDA, Agricultural Research Service","award":["2010-ST061-AG0001"],"award-info":[{"award-number":["2010-ST061-AG0001"]}]},{"name":"USDA, Agricultural Research Service","award":["P20GM130448"],"award-info":[{"award-number":["P20GM130448"]}]},{"name":"USDA, Agricultural Research Service","award":["2018-05766"],"award-info":[{"award-number":["2018-05766"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Rift Valley fever phlebovirus (RVFV) is a zoonotic pathogen that causes Rift Valley fever (RVF) in livestock and humans. Currently, there is no licensed human vaccine or antiviral drug to control RVF. Although multiple species of animals and humans are vulnerable to RVFV infection, host factors affecting susceptibility are not well understood. To identify the host factors or genes essential for RVFV replication, we conducted CRISPR-Cas9 knockout screening in human A549 cells. We then validated the putative genes using siRNA-mediated knock-downs and CRISPR-Cas9-mediated knock-out studies. The role of a candidate gene in the virus replication cycle was assessed by measuring intracellular viral RNA accumulation, and the virus titers were analyzed using plaque assay or TCID50 assay. We identified approximately 900 genes with potential involvement in RVFV infection and replication. Further evaluation of the effect of six genes on viral replication using siRNA-mediated knock-downs revealed that silencing two genes (WDR7 and LRP1) significantly impaired RVFV replication. For further analysis, we focused on the WDR7 gene since the role of the LRP1 gene in RVFV replication was previously described in detail. WDR7 knockout A549 cell lines were generated and used to dissect the effect of WRD7 on a bunyavirus, RVFV, and an orthobunyavirus, La Crosse encephalitis virus (LACV). We observed significant effects of WDR7 knockout cells on both intracellular RVFV RNA levels and viral titers. At the intracellular RNA level, WRD7 affected RVFV replication at a later phase of its replication cycle (24 h) when compared with the LACV replication, which was affected in an earlier replication phase (12 h). In summary, we identified WDR7 as an essential host factor for the replication of two different viruses, RVFV and LACV, both of which belong to the Bunyavirales order. Future studies will investigate the mechanistic role through which WDR7 facilitates phlebovirus replication.<\/jats:p>","DOI":"10.3390\/v15112251","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T08:35:52Z","timestamp":1699864552000},"page":"2251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of Host Factors for Rift Valley Fever Phlebovirus"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1671-5572","authenticated-orcid":false,"given":"Velmurugan","family":"Balaraman","sequence":"first","affiliation":[{"name":"Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine\/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabarish V.","family":"Indran","sequence":"additional","affiliation":[{"name":"Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine\/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghai","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine\/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Meekins","sequence":"additional","affiliation":[{"name":"Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine\/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laxmi U. M. R.","family":"Jakkula","sequence":"additional","affiliation":[{"name":"Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine\/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine\/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4863-5641","authenticated-orcid":false,"given":"Micheal P.","family":"Hays","sequence":"additional","affiliation":[{"name":"Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine\/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9281-894X","authenticated-orcid":false,"given":"Jayme A.","family":"Souza-Neto","sequence":"additional","affiliation":[{"name":"Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine\/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7195-785X","authenticated-orcid":false,"given":"Natasha N.","family":"Gaudreault","sequence":"additional","affiliation":[{"name":"Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine\/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip R.","family":"Hardwidge","sequence":"additional","affiliation":[{"name":"Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine\/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7877-9224","authenticated-orcid":false,"given":"William C.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Foreign Arthropod-Borne Animal Diseases Research Unit, United States Department of Agriculture, National Bio and Agro-Defense Facility, Agricultural Research Service, 1980 Denison Ave, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9737-337X","authenticated-orcid":false,"given":"Friedemann","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute for Virology, FB10\u2014Veterinary Medicine, Justus-Liebig University, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7308-5672","authenticated-orcid":false,"given":"Juergen A.","family":"Richt","sequence":"additional","affiliation":[{"name":"Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine\/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/path.1700340418","article-title":"Enzootic hepatitis or rift valley fever. 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