TY - JOUR
T1 - The Transcription and Translation Landscapes during Human Cytomegalovirus Infection Reveal Novel Host-Pathogen Interactions
AU - Tirosh, Osnat
AU - Cohen, Yifat
AU - Shitrit, Alina
AU - Shani, Odem
AU - Le-Trilling, Vu Thuy Khanh
AU - Trilling, Mirko
AU - Friedlander, Gilgi
AU - Tanenbaum, Marvin
AU - Stern-Ginossar, Noam
N1 - Publisher Copyright: © 2015 Tirosh et al.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84948945711&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.ppat.1005288
DO - https://doi.org/10.1371/journal.ppat.1005288
M3 - مقالة
C2 - 26599541
SN - 1553-7366
VL - 11
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 11
M1 - e1005288
ER -