Abstract
Emerging evidence highlights protein acetylation, a prevalent lysine posttranslational modification, as a regulatory mechanism and promising therapeutic target in human viral infections. However, how infections dynamically alter global cellular acetylation or whether viral proteins are acetylated remains virtually unexplored. Here, we establish acetylation as a highly-regulated molecular toggle of protein function integral to the herpesvirus human cytomegalovirus (HCMV) replication. We offer temporal resolution of cellular and viral acetylations. By interrogating dynamic protein acetylation with both protein abundance and subcellular localization, we discover finely tuned spatial acetylations across infection time. We determine that lamin acetylation at the nuclear periphery protects against virus production by inhibiting capsid nuclear egress. Further studies within infectious viral particles identify numerous acetylations, including on the viral transcriptional activator pUL26, which we show represses virus production. Altogether, this study provides specific insights into functions of cellular and viral protein acetylations and a valuable resource of dynamic acetylation events.
Highlights
Emerging evidence highlights protein acetylation, a prevalent lysine posttranslational modification, as a regulatory mechanism and promising therapeutic target in human viral infections
Changes in site-specific acetylations were determined by enriching acetylated peptides with anti-acetyl lysine antibodies, and analyses were performed in three biological replicates for all time points
Protein acetylation has become well-recognized as a prevalent posttranslational modifications (PTMs) that regulates core cellular pathways, including transcription, metabolism, and immune response
Summary
Emerging evidence highlights protein acetylation, a prevalent lysine posttranslational modification, as a regulatory mechanism and promising therapeutic target in human viral infections. As infection-induced changes in protein functions are linked to numerous human diseases, understanding this dynamic regulation is critical for defining the biology and pathology of virus infections Among these protein alterations during infection, accumulating evidence highlights protein lysine acetylation as a key regulatory point in mechanisms of both host antiviral response and virus replication (Fig. 1). Acetylation contributes to enzyme activity, chromatin structure, protein localization, and protein–protein interactions, and is a known regulator of transcription and metabolism[14,15] These core cellular processes are required for viral replication, suggesting that acetylation is an important molecular toggle of protein functions during infection. Small molecules that activate SIRTs inhibited the replication of HCMV, indicating that the regulation of acetylation
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