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While wild-type ORF3a disrupts endosomal acidification and limits cholesterol recycling through interaction with VPS39 (part of the HOPS complex), the Beta variant does not, allowing more efficient cholesterol recovery and stronger LDL responsiveness. Overall, our findings show that SARS-CoV-2 can directly link its replication to host cholesterol levels via ORF3a. 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AMS and JAD are inventors on a patent application filed by the Gladstone Institutes and the University of California that covers the method and composition of SARS-CoV-2 VLP preparations for RNA transduction and expression in cells. The Regents of the University of California have patents issued and pending for CRISPR technologies on which JAD is an inventor. JAD is a cofounder of\n                      \n                      ,\n                      \n                      ,\n                      \n                      ,\n                      \n                      , and\n                      \n                      . JAD is a scientific advisory board member of\n                      \n                      ,\n                      \n                      , Intellia Therapeutics, Scribe Therapeutics, Mammoth Biosciences, Algen Biotechnologies,\n                      \n                      ,\n                      \n                      and\n                      \n                      . JAD is Chief Science Advisor to Sixth Street, a Director at Johnson & Johnson, Altos, and Tempus, and has research projects sponsored by\n                      \n                      and\n                      \n                      . NJK has monetary and\/or stock compensation with the following companies: GEn1E Lifesciences, Maze Therapeutics, Mreza Therapeutics, Rezo Therapeutics, and Tenaya Therapeutics.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure and competing interests statement"}}]}}