title: The Transcription and Translation Landscapes during Human Cytomegalovirus Infection Reveal Novel Host-Pathogen Interactions.
abstract: Viruses are by definition fully dependent on the cellular translation machinery, and develop diverse mechanisms to co-opt this machinery for their own benefit. Unlike many viruses, human cytomegalovirus (HCMV) does suppress the host translation machinery, and the extent to which translation machinery contributes to the overall pattern of viral replication and pathogenesis remains elusive. Here, we combine RNA sequencing and ribosomal profiling analyses to systematically address this question. By simultaneously examining the changes in transcription and translation along HCMV infection, we uncover extensive transcriptional control that dominates the response to infection, but also diverse and dynamic translational regulation for subsets of host genes. We were also able to show that, at late time points in infection, translation of viral mRNAs is higher than that of cellular mRNAs. Lastly, integration of our translation measurements with recent measurements of protein abundance enabled comprehensive identification of dozens of host proteins that are targeted for degradation during HCMV infection. Since targeted degradation indicates a strong biological importance, this approach should be applicable for discovering central host functions during viral infection. Our work provides a framework for studying the contribution of transcription, translation and degradation during infection with any virus.
authors.affiliation: The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Osnat
authors.initials: O
authors.lastname: Tirosh
authors.affiliation: The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yifat
authors.initials: Y
authors.lastname: Cohen
authors.affiliation: The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Alina
authors.initials: A
authors.lastname: Shitrit
authors.affiliation: The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Odem
authors.initials: O
authors.lastname: Shani
authors.affiliation: Institut für Virologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Vu Thuy Khanh
authors.initials: VT
authors.lastname: Le-Trilling
authors.affiliation: Institut für Virologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Mirko
authors.initials: M
authors.lastname: Trilling
authors.affiliation: The Nancy & Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Gilgi
authors.initials: G
authors.lastname: Friedlander
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Marvin
authors.initials: M
authors.lastname: Tanenbaum
authors.affiliation: The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Stern-Ginossar
mesh_terms: D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014779:Virus Replication / Q000235:genetics*
chemical_list: D012333:RNA, Messenger