Adenovirus Remodeling of the Host Proteome and Host Factors Associated with Viral Genomes
Joseph M. Dybas, Krystal K. Lum, Katarzyna Kulej, Emigdio D. Reyes, Richard Lauman, Matthew Charman, Caitlin E. Purman, Robert T. Steinbock, Nicholas Grams, Alexander M. Price, Lydia Mendoza, Benjamin A. Garcia, Matthew D. Weitzman
Abstract
Viral infections induce myriad changes to the host cell proteome. As viruses harness cellular processes and counteract host defenses, they impact abundance, post-translational modifications, interactions, or localization of cellular proteins. Elucidating the dynamic changes to the cellular proteome during viral replication is integral to understanding how virus-host interactions influence the outcome of infection. Adenovirus encodes early gene products from the E4 genomic region that are known to alter host response pathways and promote replication, but the full extent of proteome modifications they mediate is not known. We used an integrated proteomics approach to quantitate protein abundance and protein associations with viral DNA during virus infection. Systems-level analysis identifies cellular proteins and processes impacted in an E4-dependent manner, suggesting ways that adenovirus counteracts potentially inhibitory host defenses. This study provides a global view of adenovirus-mediated proteome remodeling, which can serve as a model to investigate virus-host interactions of DNA viruses.