tetano
Editor, Senior Moderator
Cell
. 2020 Jun 17;S0092-8674(20)30630-9.
doi: 10.1016/j.cell.2020.05.035. Online ahead of print.
Hybrid Gene Origination Creates Human-Virus Chimeric Proteins During Infection
Jessica Sook Yuin Ho[SUP] 1 [/SUP], Matthew Angel[SUP] 2 [/SUP], Yixuan Ma[SUP] 1 [/SUP], Elizabeth Sloan[SUP] 3 [/SUP], Guojun Wang[SUP] 4 [/SUP], Carles Martinez-Romero[SUP] 5 [/SUP], Marta Alenquer[SUP] 6 [/SUP], Vladimir Roudko[SUP] 7 [/SUP], Liliane Chung[SUP] 8 [/SUP], Simin Zheng[SUP] 1 [/SUP], Max Chang[SUP] 9 [/SUP], Yesai Fstkchyan[SUP] 1 [/SUP], Sara Clohisey[SUP] 8 [/SUP], Adam M Dinan[SUP] 10 [/SUP], James Gibbs[SUP] 2 [/SUP], Robert Gifford[SUP] 3 [/SUP], Rong Shen[SUP] 11 [/SUP], Quan Gu[SUP] 3 [/SUP], Nerea Irigoyen[SUP] 10 [/SUP], Laura Campisi[SUP] 1 [/SUP], Cheng Huang[SUP] 12 [/SUP], Nan Zhao[SUP] 1 [/SUP], Joshua D Jones[SUP] 10 [/SUP], Ingeborg van Knippenberg[SUP] 3 [/SUP], Zeyu Zhu[SUP] 1 [/SUP], Natasha Moshkina[SUP] 1 [/SUP], L?a Meyer[SUP] 3 [/SUP], Justine Noel[SUP] 1 [/SUP], Zuleyma Peralta[SUP] 13 [/SUP], Veronica Rezelj[SUP] 3 [/SUP], Robyn Kaake[SUP] 14 [/SUP], Brad Rosenberg[SUP] 1 [/SUP], Bo Wang[SUP] 8 [/SUP], Jiajie Wei[SUP] 2 [/SUP], Slobodan Paessler[SUP] 12 [/SUP], Helen M Wise[SUP] 8 [/SUP], Jeffrey Johnson[SUP] 15 [/SUP], Alessandro Vannini[SUP] 16 [/SUP], Maria Jo?o Amorim[SUP] 6 [/SUP], J Kenneth Baillie[SUP] 8 [/SUP], Emily R Miraldi[SUP] 17 [/SUP], Christopher Benner[SUP] 9 [/SUP], Ian Brierley[SUP] 10 [/SUP], Paul Digard[SUP] 8 [/SUP], Marta Łuksza[SUP] 13 [/SUP], Andrew E Firth[SUP] 10 [/SUP], Nevan Krogan[SUP] 14 [/SUP], Benjamin D Greenbaum[SUP] 7 [/SUP], Megan K MacLeod[SUP] 18 [/SUP], Harm van Bakel[SUP] 13 [/SUP], Adolfo Garc?a-Sastre[SUP] 5 [/SUP], Jonathan W Yewdell[SUP] 2 [/SUP], Edward Hutchinson[SUP] 19 [/SUP], Ivan Marazzi[SUP] 20 [/SUP]
Affiliations
Abstract
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.
Keywords: RNA hybrid; cap-snatching; chimeric proteins; gene origination; influenza; segmented negative-strand RNA viruses; uORFs; upstream AUG; viral RNA; viral evolution.
. 2020 Jun 17;S0092-8674(20)30630-9.
doi: 10.1016/j.cell.2020.05.035. Online ahead of print.
Hybrid Gene Origination Creates Human-Virus Chimeric Proteins During Infection
Jessica Sook Yuin Ho[SUP] 1 [/SUP], Matthew Angel[SUP] 2 [/SUP], Yixuan Ma[SUP] 1 [/SUP], Elizabeth Sloan[SUP] 3 [/SUP], Guojun Wang[SUP] 4 [/SUP], Carles Martinez-Romero[SUP] 5 [/SUP], Marta Alenquer[SUP] 6 [/SUP], Vladimir Roudko[SUP] 7 [/SUP], Liliane Chung[SUP] 8 [/SUP], Simin Zheng[SUP] 1 [/SUP], Max Chang[SUP] 9 [/SUP], Yesai Fstkchyan[SUP] 1 [/SUP], Sara Clohisey[SUP] 8 [/SUP], Adam M Dinan[SUP] 10 [/SUP], James Gibbs[SUP] 2 [/SUP], Robert Gifford[SUP] 3 [/SUP], Rong Shen[SUP] 11 [/SUP], Quan Gu[SUP] 3 [/SUP], Nerea Irigoyen[SUP] 10 [/SUP], Laura Campisi[SUP] 1 [/SUP], Cheng Huang[SUP] 12 [/SUP], Nan Zhao[SUP] 1 [/SUP], Joshua D Jones[SUP] 10 [/SUP], Ingeborg van Knippenberg[SUP] 3 [/SUP], Zeyu Zhu[SUP] 1 [/SUP], Natasha Moshkina[SUP] 1 [/SUP], L?a Meyer[SUP] 3 [/SUP], Justine Noel[SUP] 1 [/SUP], Zuleyma Peralta[SUP] 13 [/SUP], Veronica Rezelj[SUP] 3 [/SUP], Robyn Kaake[SUP] 14 [/SUP], Brad Rosenberg[SUP] 1 [/SUP], Bo Wang[SUP] 8 [/SUP], Jiajie Wei[SUP] 2 [/SUP], Slobodan Paessler[SUP] 12 [/SUP], Helen M Wise[SUP] 8 [/SUP], Jeffrey Johnson[SUP] 15 [/SUP], Alessandro Vannini[SUP] 16 [/SUP], Maria Jo?o Amorim[SUP] 6 [/SUP], J Kenneth Baillie[SUP] 8 [/SUP], Emily R Miraldi[SUP] 17 [/SUP], Christopher Benner[SUP] 9 [/SUP], Ian Brierley[SUP] 10 [/SUP], Paul Digard[SUP] 8 [/SUP], Marta Łuksza[SUP] 13 [/SUP], Andrew E Firth[SUP] 10 [/SUP], Nevan Krogan[SUP] 14 [/SUP], Benjamin D Greenbaum[SUP] 7 [/SUP], Megan K MacLeod[SUP] 18 [/SUP], Harm van Bakel[SUP] 13 [/SUP], Adolfo Garc?a-Sastre[SUP] 5 [/SUP], Jonathan W Yewdell[SUP] 2 [/SUP], Edward Hutchinson[SUP] 19 [/SUP], Ivan Marazzi[SUP] 20 [/SUP]
Affiliations
- PMID: 32559462
- DOI: 10.1016/j.cell.2020.05.035
Abstract
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.
Keywords: RNA hybrid; cap-snatching; chimeric proteins; gene origination; influenza; segmented negative-strand RNA viruses; uORFs; upstream AUG; viral RNA; viral evolution.