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J. Virol. doi:10.1128/JVI.00821-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Polyoma Small T Antigen Controls Viral Chromatin Modifications Through Effects on Kinetics of Virus Growth and Cell Cycle Progression

Department of Pathology, Harvard Medical School, Boston, Massachusetts

^* To whom correspondence should be addressed. Email: thomas_benjamin{at}hms.harvard.edu.

	Abstract

Minichromosomes of wild type polyoma virus were previously shown to be highly acetylated on histones H3 and H4 compared either to bulk cell chromatin or to viral chromatin of non-transforming hr-t mutants which are defective in both the small T and middle T antigens. A series of site-directed virus mutants have been used along with antibodies to sites of histone modifications to further investigate the state of viral chromatin and its dependence on the T antigens. Small T but not middle T was important in hyperacetylation at major sites in H3 and H4. Mutants blocked in middle T signaling pathways but encoding normal small T showed a hyperacetylated pattern similar to wild-type virus. The hyperacetylation defect of hr-t mutant NG59 was partially complemented by growth of the mutant in cells expressing wild type small T. In contrast to its hypoacetylated state, NG59 minichromosomes were hypermethylated at specific lysines in H3 and also showed a higher level of phosphorylation at H3ser10, a modification associated with the late G2 and M phases of the cell cycle. Comparisons of virus growth kinetics and cell cycle progression in wild type- and NG59-infected cells showed a correlation between the phase of the cell cycle at which virus assembly occurred and histone modifications in the progeny virus. Replication and assembly of wild type virus was completed largely during S phase. Growth of NG59 was delayed by about 12 hours with assembly occurring predominately in G2. These results suggest that small T affects modifications of viral chromatin by altering the temporal coordination of virus growth and the cell cycle.