DETERMINANTS OF PARVOVIRUS ASSEMBLY AND INFECTIVITY

University Of Colorado Denver, Aurora CO

Investigators

Linked publications & trials

Abstract

The parvoviruses are small, structurally simple, single strand DNA viruses. At least one parvovirus (B19) is a human pathogen, implicated in a disease spectrum from aplastic crises to hydrops fetalis. Other parvoviruses can cause disease in animals but also possess oncosuppressive properties. Despite their structural simplicity the processes of virion assembly, including DNA packaging, and the role of the individual capsid proteins in assembly and infectivity are poorly understood. Here, parvovirus assembly and infectivity will be investigated using a novel transduction system offering major advantages over wild type virus. They have generated transducing virions by packaging recombinant genomes based on the rodent parvovirus, LuIII, with capsid proteins from related viruses, including MVM and CPV. The advantages of this system for studying viral assembly and infectivity are: (i) genetically overlapping capsid components can be provided separately, and thus mutagenized independently, which is impossible with wild type virus: (ii) infection is limited to early events so that these can be studied in isolation from genomic replication and assembly of viral progeny. The three specific aims are: 1. To determine which sequences in the N-terminal regions of the parvovirus capsid proteins, VP1 and VP2, are essential for either assembly or infectivity. 2. To test the hypothesis that there is sequence specificity in the ability of packaged DNA to trigger the conformational changes in the capsid that occur during virion maturation. 3. To investigate the mechanisms of packaging both strands (LuIII), versus only minus strand DNA (MVM, CPV), by different parvoviruses. These studies will elucidate structural determinants required for assembly and/or infectivity of parvovirus virions.