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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Experimental Virology Study Section (EVR)
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Beisel, Christopher E
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Yale University
Schools of Medicine
New Haven
United States
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Marr, Matthew; D'Abramo, Anthony; Pittman, Nikea et al. (2018) Optimizing the Targeting of Mouse Parvovirus 1 to Murine Melanoma Selects for Recombinant Genomes and Novel Mutations in the Viral Capsid Gene. Viruses 10:
Mihaylov, Ivailo S; Cotmore, Susan F; Tattersall, Peter (2014) Complementation for an essential ancillary non-structural protein function across parvovirus genera. Virology 468-470:226-37
Cotmore, Susan F; Agbandje-McKenna, Mavis; Chiorini, John A et al. (2014) The family Parvoviridae. Arch Virol 159:1239-47
Li, Lei; Cotmore, Susan F; Tattersall, Peter (2013) Parvoviral left-end hairpin ears are essential during infection for establishing a functional intranuclear transcription template and for efficient progeny genome encapsidation. J Virol 87:10501-14
Cotmore, Susan F; Tattersall, Peter (2013) Parvovirus diversity and DNA damage responses. Cold Spring Harb Perspect Biol 5:
Li, Lei; Cotmore, Susan F; Tattersall, Peter (2012) Maintenance of the flip sequence orientation of the ears in the parvoviral left-end hairpin is a nonessential consequence of the critical asymmetry in the hairpin stem. J Virol 86:12187-97
Cotmore, Susan F; Tattersall, Peter (2012) Mutations at the base of the icosahedral five-fold cylinders of minute virus of mice induce 3'-to-5' genome uncoating and critically impair entry functions. J Virol 86:69-80
Ruiz, Zandra; Mihaylov, Ivailo S; Cotmore, Susan F et al. (2011) Recruitment of DNA replication and damage response proteins to viral replication centers during infection with NS2 mutants of Minute Virus of Mice (MVM). Virology 410:375-84
Plevka, Pavel; Hafenstein, Susan; Li, Lei et al. (2011) Structure of a packaging-defective mutant of minute virus of mice indicates that the genome is packaged via a pore at a 5-fold axis. J Virol 85:4822-7
Cotmore, Susan F; Hafenstein, Susan; Tattersall, Peter (2010) Depletion of virion-associated divalent cations induces parvovirus minute virus of mice to eject its genome in a 3'-to-5' direction from an otherwise intact viral particle. J Virol 84:1945-56

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