作者
Jessica Sook Yuin Ho,Matthew Angel,Yixuan Ma,Elizabeth Sloan,Guojun Wang,Carles Martínez-Romero,Marta Alenquer,Vladimir Roudko,Liliane Chung,Simin Zheng,Max W. Chang,Yesai Fstkchyan,Sara Clohisey,Adam M. Dinan,James P. Gibbs,Robert J. Gifford,Rong Shen,Quan Gu,Nerea Irigoyen,Laura Campisi,Cheng Huang,Nan Zhao,Joshua D. Jones,Ingeborg van Knippenberg,Zeyu Zhu,Natasha Moshkina,Léa Meyer,Justine Noel,Zuleyma Peralta,Veronica V. Rezelj,Robyn M. Kaake,Brad R. Rosenberg,Bo Wang,Jiajie Wei,Slobodan Paessler,Helen M. Wise,Jeffrey R. Johnson,Alessandro Vannini,Maria João Amorim,J Kenneth Baillie,Emily R. Miraldi,Christopher Benner,Ian Brierley,Paul Digard,Marta Łuksza,Andrew E. Firth,Nevan J. Krogan,Benjamin Greenbaum,Megan K. L. MacLeod,Harm van Bakel,Adolfo García-Sastre,Jonathan W. Yewdell,Edward C. Hutchinson,Ivan Marazzi
摘要
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.