• Home
  • Publications
  • Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection

Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection


  • Ho J. S. Y.,
  • 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.,
  • Marazzi I.


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.
  • Facebook
  • Twitter
  • LinkedIn
  • Email