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- W3158703886 abstract "Summary Most restriction factors recognize virus features to execute antiviral functions. In contrast, we discovered retroCHMP3, which instead impairs the host endosomal complexes required for transport (ESCRT) pathway to inhibit budding of enveloped viruses, including HIV-1. The ESCRT pathway is essential, so ESCRT inhibition creates the potential for cytotoxicity. We chart independent courses of retroCHMP3 emergence and reduction of cytotoxicity in New World monkeys and mice using ancestral reconstructions. Overexpression of full-length CHMP3 results in modest antiviral activity, which is enhanced by truncating mutations but causes increased cytotoxicity. We show that retroCHMP3 from squirrel monkeys acquired ancient mutations mitigating cytotoxicity before gaining the activating truncation. In contrast, a truncating mutation arose soon after the independent appearance of murine retroCHMP3, but the variant exhibits regulated expression by interferon signaling, illustrating distinct paths in the emergence of antiviral functions. RetroCHMP3 genes can repeatedly emerge in different species to independently create new immune functions." @default.
- W3158703886 created "2021-05-10" @default.
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- W3158703886 date "2021-04-27" @default.
- W3158703886 modified "2023-10-14" @default.
- W3158703886 title "Recurrent Emergence of an Antiviral Defense through Repeated Retrotransposition and Truncation of CHMP3" @default.
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- W3158703886 doi "https://doi.org/10.1101/2021.04.27.441704" @default.
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