MOLECULAR GENETICS OF PARVOVIRAL DNA REPLICATION

Yale University, New Haven CT

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Abstract

DESCRIPTION: Autonomous parvoviruses such as the Minute Virus of Mice (MVM) have single-strand DNA genomes and replicate exclusively in dividing cell populations. The long term goal of this research effort is to understand the molecular mechanism that this class of viruses use to unpackage and replicate their DNA in infected cells. MVM can be replicated by human proteins both in vivo and in vitro, if its own replicator protein NS1 is present. One aim of the proposed work will be to characterize human cell proteins that are required for replication. One of these factors is a novel protein heterodimer that binds to repeat motifs in the DNA genome. The mechanism by which concatemeric duplex replication intermediates are resolved to generate unit length molecules will also be studied. A new in vitro system for unpackaging virus DNA will also be explored. Lastly, analysis of functional domains in the NS1 protein will be continued to understand its role as an initiator of MVM replication.