Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection

Ho, Jessica Sook Yuin; Angel, Matthew; Ma, Yixuan; Sloan, Elizabeth; Wang, Guojun; Martinez-Romero, Carles; Alenquer, Marta; Roudko, Vladimir; Chung, Liliane; Zheng, Simin; Chang, Max; Fstkchyan, Yesai; Clohisey, Sara; Dinan, Adam M.; Gibbs, James; Gifford, Robert; Shen, Rong; Gu, Quan; Irigoyen, Nerea; Campisi, Laura; Huang, Cheng; Zhao, Nan; Jones, Joshua D.; van Knippenberg, Ingeborg; Zhu, Zeyu; Moshkina, Natasha; Meyer, L�a; Noel, Justine; Peralta, Zuleyma; Rezelj, Veronica; Kaake, Robyn; Rosenberg, Brad; Wang, Bo; Wei, Jiajie; Paessler, Slobodan; Wise, Helen M.; Johnson, Jeffrey; Vannini, Alessandro; Amorim, Maria Jo�o; Baillie, J. Kenneth; Miraldi, Emily R.; Benner, Christopher; Brierley, Ian; Digard, Paul; ?uksza, Marta; Firth, Andrew E.; Krogan, Nevan; Greenbaum, Benjamin D.; MacLeod, Megan K.; van Bakel, Harm; Garc�a-Sastre, Adolfo; Yewdell, Jonathan W.; Hutchinson, Edward; Marazzi, Ivan

Abstract

RNA viruses are a major human health threat. The life cycles of many highly pathogenic RNA viruses like influ-enza A virus (IAV) and Lassa virus depends on host mRNA, because viral polymerases cleave 50-m7G-cappedhost transcripts to prime viral mRNA synthesis (‘‘cap-snatching’’). We hypothesized that start codons withincap-snatched host transcripts could generate chimeric human-viral mRNAs with coding potential. We reportthe existence of this mechanism of gene origination, which we named ‘‘start-snatching.’’ Depending on thereading frame, start-snatching allows the translation of host and viral ‘‘untranslated regions’’ (UTRs) to createN-terminally extended viral proteins or entirely novel polypeptides by genetic overprinting. We show thatboth types of chimeric proteins are made in IAV-infected cells, generate T cell responses, and contributeto virulence. Our results indicate that during infection with IAV, and likely a multitude of other human, animaland plant viruses, a host-dependent mechanism allows the genesis of hybrid genes.

Citation

Ho, J. S. Y., Angel, M., Ma, Y., Sloan, E., Wang, G., Martinez-Romero, C., …Marazzi, I. (2020). Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection. Cell, 181(7), 1502-1517. https://doi.org/10.1016/j.cell.2020.05.035

• Journal Article Type: Article
• Acceptance Date: May 18, 2020
• Online Publication Date: Jun 18, 2020
• Publication Date: 2020-06
• Deposit Date: Jul 22, 2020
• Publicly Available Date: Jul 22, 2020
• Journal: Cell
• Print ISSN: 0092-8674
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 181
• Issue: 7
• Pages: 1502-1517
• DOI: https://doi.org/10.1016/j.cell.2020.05.035
• Keywords: General Biochemistry, Genetics and Molecular Biology
• Public URL: http://researchrepository.napier.ac.uk/Output/2677131