Jessica Sook Yuin Ho
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
Authors
Matthew Angel
Yixuan Ma
Elizabeth Sloan
Guojun Wang
Carles Martinez-Romero
Marta Alenquer
Vladimir Roudko
Liliane Chung
Simin Zheng
Max Chang
Yesai Fstkchyan
Sara Clohisey
Adam M. Dinan
James Gibbs
Robert Gifford
Rong Shen
Quan Gu
Nerea Irigoyen
Laura Campisi
Cheng Huang
Nan Zhao
Joshua D. Jones
Ingeborg van Knippenberg
Zeyu Zhu
Natasha Moshkina
L�a Meyer
Justine Noel
Zuleyma Peralta
Veronica Rezelj
Robyn Kaake
Brad Rosenberg
Bo Wang
Jiajie Wei
Slobodan Paessler
Helen M. Wise
Jeffrey Johnson
Alessandro Vannini
Maria Jo�o Amorim
J. Kenneth Baillie
Emily R. Miraldi
Christopher Benner
Ian Brierley
Paul Digard
Marta ?uksza
Andrew E. Firth
Nevan Krogan
Benjamin D. Greenbaum
Megan K. MacLeod
Harm van Bakel
Adolfo Garc�a-Sastre
Jonathan W. Yewdell
Edward Hutchinson
Ivan Marazzi
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., Alenquer, M., Roudko, V., Chung, L., Zheng, S., Chang, M., Fstkchyan, Y., Clohisey, S., Dinan, A. M., Gibbs, J., Gifford, R., Shen, R., Gu, Q., Irigoyen, N., Campisi, L., …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 |
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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
Copyright Statement
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).