1. Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection.
- Author
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Ho JSY, Angel M, Ma Y, Sloan E, Wang G, Martinez-Romero C, Alenquer M, Roudko V, Chung L, Zheng S, Chang M, Fstkchyan Y, Clohisey S, Dinan AM, Gibbs J, Gifford R, Shen R, Gu Q, Irigoyen N, Campisi L, Huang C, Zhao N, Jones JD, van Knippenberg I, Zhu Z, Moshkina N, Meyer L, Noel J, Peralta Z, Rezelj V, Kaake R, Rosenberg B, Wang B, Wei J, Paessler S, Wise HM, Johnson J, Vannini A, Amorim MJ, Baillie JK, Miraldi ER, Benner C, Brierley I, Digard P, Łuksza M, Firth AE, Krogan N, Greenbaum BD, MacLeod MK, van Bakel H, Garcìa-Sastre A, Yewdell JW, Hutchinson E, and Marazzi I
- Subjects
- 5' Untranslated Regions genetics, Animals, Cattle, Cell Line, Cricetinae, Dogs, Humans, Influenza A virus metabolism, Mice, Mutant Chimeric Proteins genetics, Mutant Chimeric Proteins metabolism, Open Reading Frames genetics, RNA Caps metabolism, RNA Virus Infections metabolism, RNA Viruses genetics, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Viral metabolism, RNA-Dependent RNA Polymerase genetics, RNA-Dependent RNA Polymerase metabolism, Recombinant Fusion Proteins metabolism, Transcription, Genetic genetics, Viral Proteins metabolism, Virus Replication genetics, RNA Caps genetics, RNA Virus Infections genetics, Recombinant Fusion Proteins genetics
- Abstract
RNA viruses are a major human health threat. The life cycles of many highly pathogenic RNA viruses like influenza A virus (IAV) and Lassa virus depends on host mRNA, because viral polymerases cleave 5'-m7G-capped host transcripts to prime viral mRNA synthesis ("cap-snatching"). We hypothesized that start codons within cap-snatched host transcripts could generate chimeric human-viral mRNAs with coding potential. We report the existence of this mechanism of gene origination, which we named "start-snatching." Depending on the reading frame, start-snatching allows the translation of host and viral "untranslated regions" (UTRs) to create N-terminally extended viral proteins or entirely novel polypeptides by genetic overprinting. We show that both types of chimeric proteins are made in IAV-infected cells, generate T cell responses, and contribute to virulence. Our results indicate that during infection with IAV, and likely a multitude of other human, animal and plant viruses, a host-dependent mechanism allows the genesis of hybrid genes., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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