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| Status |
Public on May 15, 2020 |
| Title |
HUMAN-VIRUS CHIMERIC PROTEINS GENERATED DURING INFECTION |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
RNA viruses are a major threat to global human health. The life cycles of many highly pathogenic RNA viruses like influenza A virus (IAV) and Lassa virus depends on host mRNA, as 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 drive the expression of chimeric human-viral coding sequences. Here, we report the existence of this mechanism of gene origination (‘start-snatching’), which creates, depending on the translatability of the viral UTRs, human-virus protein chimeras either as 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, can generate T cell responses and contribute to virulence. Our results indicate that IAV, and likely a multitude of other human-, animal- and plant-viruses, use this host-dependent mechanism to expand their proteome diversity during infection.
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| Overall design |
Ribosome profiling of influenza A infected cells
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| Contributor(s) |
Ho JS, Angel M, Ma Y, Sloan E, Wang G, Martinez-Romero C, Alenquer M, Campisi L, Chung L, Zheng S, Chang M, Fstkchyan Y, Clohisey S, Dinan AM, Gibbs J, Gifford R, Shen R, Gu Q, Irigoyen N, Roudko V, Cheng H, Zhao N, Jones JD, van Knippenberg I, 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 |
| Citation(s) |
32559462 |
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| Submission date |
Apr 07, 2020 |
| Last update date |
Jul 07, 2020 |
| Contact name |
George Pavlakis |
| E-mail(s) |
george.pavlakis@nih.gov
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| Phone |
301-846-1474
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| Organization name |
NCI
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| Department |
Vaccine Branch
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| Lab |
Pavlakis
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| Street address |
535 Sultan St
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| City |
Frederick |
| State/province |
MD |
| ZIP/Postal code |
21702 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA623585 |
| SRA |
SRP255621 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE148245_RAW.tar |
1.2 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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