Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection.
View/ Open
Date
2020-06-25Author
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
Marazzi, I
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Research team
Vannini Group
Language
eng
Date accepted
2020-05-18
License start date
2020-06-18
Citation
Cell, 2020, 181 (7), pp. 1502 - 1517.e23
Publisher
CELL PRESS