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)
|
Text
216298.pdf - Published Version Available under License Creative Commons Attribution. 3MB |
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 Van Knippenberg, Dr Ingeborg and Hutchinson, Dr Edward and Macleod, Dr Megan and Wang, Dr Bo and Rezelj, Veronica Valentina and Sloan, Dr Elizabeth |
| 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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| 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 |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information