Precursor of human adenovirus core polypeptide Mu targets the nucleolus and modulates the expression of E2 proteins

• Published in: Journal of general virology 2004-01, Vol.85 (1), p.185-196
• Main Authors: Lee, T. W. R, Lawrence, F. J, Dauksaite, V, Akusjarvi, G, Blair, G. E, Matthews, D. A
• Format: Article
• Language: English
• Subjects: Adenovirus E2 Proteins - metabolism; Adenoviruses, Human - pathogenicity; AE2 protein; Amino Acid Sequence; AMu protein; Biological and medical sciences; Cell Nucleolus - metabolism; DNA-Binding Proteins - metabolism; E2 protein; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene Expression Regulation, Viral; Green Fluorescent Proteins; HeLa Cells; Human adenovirus 2; Humans; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Luminescent Proteins/genetics/metabolism; Microbiology; Miscellaneous; Molecular Sequence Data; Mu protein; Peptides - metabolism; Protein Precursors - metabolism; Recombinant Fusion Proteins - metabolism; terminal protein; Viral Core Proteins - metabolism; Virology
• ISSN: 0022-1317; 1465-2099; 1465-2099
• DOI: 10.1099/vir.0.19352-0

1 School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK 2 Division of Virology, Department of Pathology and Microbiology, University Walk, Bristol University, Bristol BS8 1TD, UK 3 Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, S-75123 Uppsala, Sweden Correspondence David Matthews d.a.matthews{at}bristol.ac.uk We have examined the subcellular localization properties of human adenovirus 2 (HAdV-2) preMu and mature Mu (pX) proteins as fusions with enhanced green fluorescence protein (EGFP). We determined that preMu is exclusively a nucleolar protein with a single nucleolar accumulation signal within the Mu sequence. In addition, we noted that both preMu–EGFP and Mu–EGFP are excluded from adenovirus DNA-binding protein (DBP)-rich replication centres in adenovirus-infected cells. Surprisingly, we observed that cells in which preMu–EGFP (but not Mu–EGFP) is transiently expressed prior to or shortly after infection with Ad2 did not express late adenovirus genes. Further investigation suggested this might be due to a failure to express pre-terminal protein (preTP) from the E2 region, despite expression of another E2 protein, DBP. Deletion mutagenesis identified a highly conserved region in the C terminus of preMu responsible for these observations. Thus our data suggest that preMu may play a role in modulating accumulation of proteins from the E2 region.