期刊
CELL
卷 181, 期 7, 页码 1502-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.05.035
关键词
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资金
- Burroughs Wellcome Fund (United States) [1017892]
- Chan Zuckerberg Initiative (United States) [2018-191895]
- NIH (United States) [R01AI113186]
- NIH [U19AI135972]
- MRC (United Kingdom) Career Development Award [MR/N008618/1]
- MRC Programme Grant [MR/K000241/1]
- Wellcome Trust (United Kingdom) Senior Investigator award [099220/Z/12/Z]
- MRC [MR/M011747/1, MC_UU_12014/12]
- Wellcome Trust Intermediate Clinical Fellowship [103258/Z/13/Z]
- Wellcome-Beit Prize [103258/Z/13/A]
- UK Intensive Care Society
- BBSRC (United Kingdom) Institute Strategic Programme Grant
- SHIELD Edinburgh Global Research Scholarship [MR/N02995X/1]
- Wellcome Trust [106207]
- European Research Council (European Union) [646891]
- BBSRC Institute Strategic Programme [BB/J004324/1, BB/P013740/1]
- FCT (Portugal) [PTDC/BIA-CEL/32211/2017, IF/00899/2013]
- Wellcome Investigator Award [210703/Z/18/Z]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI001210] Funding Source: NIH RePORTER
- Fundação para a Ciência e a Tecnologia [PTDC/BIA-CEL/32211/2017] Funding Source: FCT
- BBSRC [BBS/E/D/20002173] Funding Source: UKRI
- MRC [MR/K000241/1, MC_UU_12014/9, MR/M011747/1, MC_UU_12014/12, MR/N008618/1] Funding Source: UKRI
- European Research Council (ERC) [646891] Funding Source: European Research Council (ERC)
- Wellcome Trust [210703/Z/18/Z, 099220/Z/12/Z, 103258/Z/13/A] Funding Source: Wellcome Trust
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.
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