A Portrait of the Human Organelle Proteome In Space and Time during Cytomegalovirus Infection.

TitleA Portrait of the Human Organelle Proteome In Space and Time during Cytomegalovirus Infection.
Publication TypeJournal Article
Year of Publication2016
AuthorsBeltran, PMJean, Mathias, RA, Cristea, IM
JournalCell Syst
Volume3
Issue4
Pagination361-373.e6
Date Published2016 10 26
ISSN2405-4712
KeywordsCytomegalovirus Infections, Humans, Organelles, Proteome, Virus Replication
Abstract

<p>The organelles within a eukaryotic host are manipulated by viruses to support successful virus replication and spread of infection, yet the global impact of viral infection on host organelles is poorly understood. Integrating microscopy, subcellular fractionation, mass spectrometry, and functional analyses, we conducted a cell-wide study of organelles in primary fibroblasts throughout the time course of human cytomegalovirus (HCMV) infection. We used label-free and isobaric-labeling proteomics to characterize nearly 4,000 host and 100 viral proteins, then classified their specific subcellular locations over time using machine learning. We observed a global reorganization of proteins across the secretory pathway, plasma membrane, and mitochondria, including reorganization and processing of lysosomal proteins into distinct subpopulations and translocations of individual proteins between organelles at specific time points. We also demonstrate that MYO18A, an unconventional myosin that translocates from the plasma membrane to the viral assembly complex, is necessary for efficient HCMV replication. This study provides a comprehensive resource for understanding host and virus biology during HCMV pathogenesis.</p>

DOI10.1016/j.cels.2016.08.012
Alternate JournalCell Syst
PubMed ID27641956
PubMed Central IDPMC5083158
Grant ListR01 GM114141 / GM / NIGMS NIH HHS / United States
R01 HL127640 / HL / NHLBI NIH HHS / United States
R21 AI102187 / AI / NIAID NIH HHS / United States