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• W3204715211 abstract "Abstract Cholesterol homeostasis is required for the replication of many viruses, including Ebola virus, hepatitis C virus, and human immunodeficiency virus-1. Niemann-Pick C1 (NPC1) is an endosomal-lysosomal membrane protein involved in cholesterol trafficking from late endosomes and lysosomes to the endoplasmic reticulum. We identified NPC1 in CRISPR and RNA interference screens as a putative host factor for infection by mammalian orthoreovirus (reovirus). Following internalization via clathrin-mediated endocytosis, the reovirus outer capsid is proteolytically removed, the endosomal membrane is disrupted, and the viral core is released into the cytoplasm where viral transcription, genome replication, and assembly take place. We found that reovirus infection is significantly impaired in cells lacking NPC1, but infection is restored by treatment of cells with hydroxypropyl-β-cyclodextrin, which binds and solubilizes cholesterol. Absence of NPC1 did not dampen infection by infectious subvirion particles, which are reovirus disassembly intermediates that bypass the endocytic pathway for infection of target cells. NPC1 is not required for reovirus attachment to the plasma membrane, internalization into cells, or uncoating within endosomes. Instead, NPC1 is required for delivery of transcriptionally active reovirus core particles into the cytoplasm. These findings suggest that cholesterol homeostasis, ensured by NPC1 transport activity, is required for reovirus penetration into the cytoplasm, pointing to a new function for NPC1 and cholesterol homeostasis in viral infection. Author summary Genetic screens are useful strategies to identify host factors required for viral infection. NPC1 was identified in independent CRISPR and RNA interference screens as a putative host factor required for reovirus replication. We discovered that NPC1-mediated cholesterol transport is dispensable for reovirus attachment, internalization, and disassembly but required for penetration of the viral disassembly intermediate from late endosomes into the cytoplasm. These findings pinpoint an essential function for cholesterol in the entry of reovirus and raise the possibility that cholesterol homeostasis regulates the entry of other viruses that penetrate late endosomes to initiate replication." @default.
• W3204715211 created "2021-10-11" @default.
• W3204715211 creator A5000958618 @default.
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• W3204715211 date "2021-09-28" @default.
• W3204715211 modified "2023-10-14" @default.
• W3204715211 title "Reovirus infection is regulated by NPC1 and endosomal cholesterol homeostasis" @default.
• W3204715211 cites W1517980685 @default.
• W3204715211 cites W1563945198 @default.
• W3204715211 cites W1575702291 @default.
• W3204715211 cites W1654444165 @default.
• W3204715211 cites W1760776415 @default.
• W3204715211 cites W1952957089 @default.
• W3204715211 cites W1969261348 @default.
• W3204715211 cites W1970849988 @default.
• W3204715211 cites W1976528399 @default.
• W3204715211 cites W1982097445 @default.
• W3204715211 cites W1984945390 @default.
• W3204715211 cites W1995583822 @default.
• W3204715211 cites W1997019840 @default.
• W3204715211 cites W2003796402 @default.
• W3204715211 cites W2007767060 @default.
• W3204715211 cites W2018894811 @default.
• W3204715211 cites W2028658614 @default.
• W3204715211 cites W2032148650 @default.
• W3204715211 cites W2036378627 @default.
• W3204715211 cites W2048172399 @default.
• W3204715211 cites W2051245442 @default.
• W3204715211 cites W2058498150 @default.
• W3204715211 cites W2059296004 @default.
• W3204715211 cites W2065408118 @default.
• W3204715211 cites W2068262899 @default.
• W3204715211 cites W2072253684 @default.
• W3204715211 cites W2078583436 @default.
• W3204715211 cites W2082834676 @default.
• W3204715211 cites W2086871300 @default.
• W3204715211 cites W2090197330 @default.
• W3204715211 cites W2095433366 @default.
• W3204715211 cites W2101200006 @default.
• W3204715211 cites W2101711240 @default.
• W3204715211 cites W2106913518 @default.
• W3204715211 cites W2109055236 @default.
• W3204715211 cites W2109512206 @default.
• W3204715211 cites W2110811665 @default.
• W3204715211 cites W2110951885 @default.
• W3204715211 cites W2114283220 @default.
• W3204715211 cites W2115716807 @default.
• W3204715211 cites W2117582775 @default.
• W3204715211 cites W2124700590 @default.
• W3204715211 cites W2131553729 @default.
• W3204715211 cites W2134893181 @default.
• W3204715211 cites W2136116905 @default.
• W3204715211 cites W2138132983 @default.
• W3204715211 cites W2141226555 @default.
• W3204715211 cites W2142630646 @default.
• W3204715211 cites W2145386287 @default.
• W3204715211 cites W2147726295 @default.
• W3204715211 cites W2153532750 @default.
• W3204715211 cites W2158062405 @default.
• W3204715211 cites W2160360322 @default.
• W3204715211 cites W2176155893 @default.
• W3204715211 cites W2252568502 @default.
• W3204715211 cites W2258585930 @default.
• W3204715211 cites W2261822942 @default.
• W3204715211 cites W2268380397 @default.
• W3204715211 cites W2280108344 @default.
• W3204715211 cites W2288648350 @default.
• W3204715211 cites W2316191615 @default.
• W3204715211 cites W2460640366 @default.
• W3204715211 cites W2511665693 @default.
• W3204715211 cites W2529794991 @default.
• W3204715211 cites W2551044271 @default.
• W3204715211 cites W2604301236 @default.
• W3204715211 cites W2606737810 @default.
• W3204715211 cites W2614446987 @default.
• W3204715211 cites W2744065025 @default.
• W3204715211 cites W2766222975 @default.
• W3204715211 cites W2802836506 @default.
• W3204715211 cites W2885040017 @default.
• W3204715211 cites W2911796189 @default.
• W3204715211 cites W2916326470 @default.
• W3204715211 cites W3007744741 @default.
• W3204715211 cites W3090871378 @default.
• W3204715211 cites W3093731347 @default.
• W3204715211 cites W3120602059 @default.
• W3204715211 cites W3123750342 @default.
• W3204715211 cites W3135661508 @default.
• W3204715211 cites W3176824724 @default.
• W3204715211 cites W3204632650 @default.

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