The Transcription and Translation Landscapes during Human Cytomegalovirus Infection Reveal Novel Host-Pathogen Interactions

PLoS Pathogens

Marvin Tanenbaum¹  Vu Thuy Khanh Le-Trilling²  Mirko Trilling²  Noam Stern-Ginossar³  Osnat Tirosh³  Odem Shani³  Yifat Cohen³  Alina Shitrit³  Gilgi Friedlander⁴ 

[1] Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, United States of America;Institut für Virologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany;The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel;The Nancy & Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel

关键词: Protein translation;    Messenger RNA;    Genetic footprinting;    Ribosomes;    Gene expression;    Small interfering RNAs;    Gene regulation;    Virus effects on host gene expression;   

DOI  :  10.1371/journal.ppat.1005288

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY