Research Output

Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection

  RNA viruses are a major human health threat. The life cycles of many highly pathogenic RNA viruses like influ-enza A virus (IAV) and Lassa virus depends on host mRNA, because viral polymerases cleave 50-m7G-cappedhost transcripts to prime viral mRNA synthesis (‘‘cap-snatching’’). We hypothesized that start codons withincap-snatched host transcripts could generate chimeric human-viral mRNAs with coding potential. We reportthe existence of this mechanism of gene origination, which we named ‘‘start-snatching.’’ Depending on thereading frame, start-snatching allows the translation of host and viral ‘‘untranslated regions’’ (UTRs) to createN-terminally extended viral proteins or entirely novel polypeptides by genetic overprinting. We show thatboth types of chimeric proteins are made in IAV-infected cells, generate T cell responses, and contributeto virulence. Our results indicate that during infection with IAV, and likely a multitude of other human, animaland plant viruses, a host-dependent mechanism allows the genesis of hybrid genes.

  • Type:

    Article

  • Date:

    18 June 2020

  • Publication Status:

    Published

  • Publisher

    Elsevier BV

  • DOI:

    10.1016/j.cell.2020.05.035

  • Cross Ref:

    S0092867420306309

  • ISSN:

    0092-8674

  • Funders:

    Chan Zuckerberg Initiative; Burroughs Wellcome Fund; National Institutes of Health; Medical Research Council; Wellcome Trust; Biotechnology and Biological Sciences Research Council; European Research Council; Wellcome-Beit; UK Intensive Care Society; SHIELD; Edinburgh Global Research; BBSRC Institute Strategic Programme; Wellcome Investigator Award

Citation

Ho, J. S. Y., Angel, M., Ma, Y., Sloan, E., Wang, G., Martinez-Romero, C., …Marazzi, I. (2020). Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection. Cell, 181(7), 1502-1517. https://doi.org/10.1016/j.cell.2020.05.035

Authors

Keywords

General Biochemistry, Genetics and Molecular Biology

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