mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

ABSTRACT Human adenoviruses are double-stranded DNA viruses that replicate in the cell nucleus and induce formation of replication compartments (RCs) critical viral control virus-host interactions. RCs specialized virus-induced subnuclear microenvironments where not only genome expression orchestrated but also host proteins restrict co-opted subverted. The protein composition these remains largely unexplored. In this study, we isolated adenovirus RC-enriched fractions from infected cells at different times post-infection employed a tandem mass tag-based quantitative spectrometry approach to identify associated with (data available via ProteomeXchange identifier PXD051745). These findings reveal an elaborate network potentially relevant for RC function. To validate RC-protein components identified by spectrometry, immunofluorescence immunoblotting techniques. Proteins previously described colocalize were fractions. addition, validated newly RCs, including high mobility group box 1 (HMGB1), SET nuclear proto-oncogene, structure-specific recognition (SSRP1), CCCTC-binding (CTCF), sirtuin 6 (SIRT6). We HMGB1 as binds binding (DBP). Using shRNA knockdowns inhibitors, demonstrated acts proviral factor, promoting efficient synthesis progeny production. Our data further suggest potential candidate targets therapeutic intervention provide mechanistic insights into molecular basis IMPORTANCE serve models studying respiratory have provided gene expression, well processes coordinated within known RCs. conducted proteome analyses human species C type 5, revealing multifaceted participate regulation damage response, RNA metabolism, innate immunity, other cellular antiviral defense mechanisms. Furthermore, localization several using microscopy factor late during infection. represent first analysis proteomes enhance our understanding organization infection shed light on complex interplay between factors

Language: Английский