病毒基因竟会和人类基因融合到一起，产生未知的新蛋白

论文标题：Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection

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

期刊：Cell

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日期：2020-06-19

数字识别码：10.1016/j.cell.2020.05.035

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 50 -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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所属学科：

生物

病毒学