31 Polyomavirus

Abstract

Viruses of the Polyomaviridae family contain a double-stranded, covalently closed circular DNA (~5 kb), condensed with histones into a minichromosome that is enclosed in a nonenveloped icosahedral capsid roughly 45 nm in diameter. Polyomaviruses infect species ranging from birds to humans and share a common genetic organization, but each has distinguishing features. The replication of polyomaviral DNA, especially simian virus 40 (SV40) DNA, has served as a powerful model system to identify the host replication proteins involved in viral DNA replication and to characterize the mechanism of replication. Detailed investigation of the proteins involved is beginning to provide insight into the replication process at the atomic level. In this chapter, we focus on SV40 DNA replication to illustrate advances in understanding polyomavirus DNA replication during the past decade. We then review the role of polyomaviruses in disease.

Like most viral infections, SV40 infection is characterized by a series of ordered molecular events that are spatially and temporally coordinated. Following virus attachment to a permissive cell, penetration, and uncoating, viral chromatin is transcribed in the nucleus by the cellular transcription apparatus. The single early transcript is differentially spliced to yield two major mRNAs, one encoding a protein of 708 amino acids called large tumor antigen (T antigen or Tag) and the other encoding the 174-amino acid small tumor antigen (t antigen). Tag is essential to drive infected cells into S phase, G₂, and endoreduplication (Okubo et al. 2003 and references therein); to initiate and complete viral DNA replication; to activate the...