{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T02:13:49Z","timestamp":1782267229896,"version":"3.54.5"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T00:00:00Z","timestamp":1714694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 AI069000"],"award-info":[{"award-number":["R01 AI069000"]}]},{"name":"NIH","award":["R01 AI140186"],"award-info":[{"award-number":["R01 AI140186"]}]},{"name":"NIH","award":["R01 AI141970"],"award-info":[{"award-number":["R01 AI141970"]}]},{"name":"NIH","award":["R01 AI130123"],"award-info":[{"award-number":["R01 AI130123"]}]},{"name":"NIH","award":["RJF\/2022\/000118"],"award-info":[{"award-number":["RJF\/2022\/000118"]}]},{"name":"Department of Science and Technology, India","award":["R01 AI069000"],"award-info":[{"award-number":["R01 AI069000"]}]},{"name":"Department of Science and Technology, India","award":["R01 AI140186"],"award-info":[{"award-number":["R01 AI140186"]}]},{"name":"Department of Science and Technology, India","award":["R01 AI141970"],"award-info":[{"award-number":["R01 AI141970"]}]},{"name":"Department of Science and Technology, India","award":["R01 AI130123"],"award-info":[{"award-number":["R01 AI130123"]}]},{"name":"Department of Science and Technology, India","award":["RJF\/2022\/000118"],"award-info":[{"award-number":["RJF\/2022\/000118"]}]},{"name":"Jawaharlal Nehru Centre for Advanced Scientific Research, India","award":["R01 AI069000"],"award-info":[{"award-number":["R01 AI069000"]}]},{"name":"Jawaharlal Nehru Centre for Advanced Scientific Research, India","award":["R01 AI140186"],"award-info":[{"award-number":["R01 AI140186"]}]},{"name":"Jawaharlal Nehru Centre for Advanced Scientific Research, India","award":["R01 AI141970"],"award-info":[{"award-number":["R01 AI141970"]}]},{"name":"Jawaharlal Nehru Centre for Advanced Scientific Research, India","award":["R01 AI130123"],"award-info":[{"award-number":["R01 AI130123"]}]},{"name":"Jawaharlal Nehru Centre for Advanced Scientific Research, India","award":["RJF\/2022\/000118"],"award-info":[{"award-number":["RJF\/2022\/000118"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The dengue virus is a single-stranded, positive-sense RNA virus that infects ~400 million people worldwide. Currently, there are no approved antivirals available. CRISPR-based screening methods have greatly accelerated the discovery of host factors that are essential for DENV infection and that can be targeted in host-directed antiviral interventions. In the present study, we performed a focused CRISPR (Clustered Regularly Interspaced Palindromic Repeats) library screen to discover the key host factors that are essential for DENV infection in human Huh7 cells and identified the Protein Activator of Interferon-Induced Protein Kinase (PACT) as a novel pro-viral factor for DENV. PACT is a double-stranded RNA-binding protein generally known to activate antiviral responses in virus-infected cells and block viral replication. However, in our studies, we observed that PACT plays a pro-viral role in DENV infection and specifically promotes viral RNA replication. Knockout of PACT resulted in a significant decrease in DENV RNA and protein abundances in infected cells, which was rescued upon ectopic expression of full-length PACT. An analysis of global gene expression changes indicated that several ER-associated pro-viral genes such as ERN1, DDIT3, HERPUD1, and EIF2AK3 are not upregulated in DENV-infected PACT knockout cells as compared to infected wildtype cells. Thus, our study demonstrates a novel role for PACT in promoting DENV replication, possibly through modulating the expression of ER-associated pro-viral genes.<\/jats:p>","DOI":"10.3390\/v16050725","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T03:43:46Z","timestamp":1714707826000},"page":"725","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["CRISPR Screen Reveals PACT as a Pro-Viral Factor for Dengue Viral Replication"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4734-6140","authenticated-orcid":false,"given":"Shwetha","family":"Shivaprasad","sequence":"first","affiliation":[{"name":"Department of Microbiology & Immunology, Stanford University SOM, Stanford, CA 94305, USA"},{"name":"Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru 560064, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Stanford University SOM, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Feng","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Stanford University SOM, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavithra","family":"Umashankar","sequence":"additional","affiliation":[{"name":"Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru 560064, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan E.","family":"Carette","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Stanford University SOM, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2043-2770","authenticated-orcid":false,"given":"Peter","family":"Sarnow","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Stanford University SOM, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0140-6736(23)00226-X","article-title":"The resurgence of dengue epidemic and climate change in India","volume":"401","author":"Mondal","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lee, M.F., Wu, Y.S., and Poh, C.L. 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