from Part II - Basic virology and viral gene effects on host cell functions: betaherpesviruses
Published online by Cambridge University Press: 24 December 2009
Overview
Much of the current understanding of betaherpesvirus DNA synthesis is based on studies with the cytomegaloviruses and is further shaped by comparison with prototypic alpha- and gammaherpesviruses. As for all herpesviruses, betaherpesvirus DNA synthesis occurs in the nucleus and relies on a core set of virus-coded proteins composing the replication fork machinery (detailed later) working together with trans-acting functions that promote initiation on a genetically defined, cis-acting replicator, called oriLyt. DNA synthesis initiates in the vicinity of oriLyt as soon as essential virus coded proteins appear, producing high molecular weight replication intermediates whose structure has not been fully characterized. Onset of viral DNA synthesis licenses transcription of a subset of the late class of viral genes, many of which encode proteins that assemble and constitute the complex virion. Subsequently, replication intermediates are resolved, and the progeny genomes are packaged into preformed capsids and mature ends are formed by the encapsidation machinery. Because these replication functions are essential for viral replication and pathogenesis, and differ from host counterparts, they have been candidate targets for the development of antiviral drugs. Moreover, further study of DNA replication and encapsidation may provide new insights about cellular components that contribute to these processes. Our goals in this chapter are to provide an up-to-date summary of betaherpesvirus lytic-phase replication machinery, to highlight emerging contrasts to other herpesviruses, and to consider how DNA synthesis-dependent late gene expression is regulated.
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