Hybrid gene origination creates human-virus chimeric proteins during infection

Sook Yuin Ho, J. et al. (2020) Hybrid gene origination creates human-virus chimeric proteins during infection. Cell, 181(7), 1502-1517.e23. (doi: 10.1016/j.cell.2020.05.035) (PMID:32559462) (PMCID:PMC7323901)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gifford, Dr Robert and Meyer, Dr Lea and Gu, Dr Quan and Wang, Dr Bo and Rezelj, Veronica Valentina and Van Knippenberg, Dr Ingeborg and Sloan, Dr Elizabeth and Hutchinson, Dr Edward
Authors: Sook Yuin Ho, J., 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., Huang, C., Zhao, N., Jones, J. D., 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, H. M., Johnson, J., Vannini, A., Amorim, M. J., Baillie, J. K., Miraldi, E. R., Benner, C., Brierley, I., Digard, P., Łuksza, M., Firth, A. E., Krogan, N., Greenbaum, B. D., MacLeod, M. K., van Bakel, H., Garcìa-Sastre, A., Yewdell, J. W., Hutchinson, E., and Marazzi, I.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cell
Publisher:Elsevier (Cell Press)
ISSN:0092-8674
ISSN (Online):1097-4172
Published Online:18 June 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Cell 181(7):1502-1517.e23
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172398Functional investigations of the influenza virus proteomeEdward HutchinsonMedical Research Council (MRC)MR/N008618/1III-MRC-GU Centre for Virus Research