Over the last granting period we have nearly completed characterization of the transcription profiles of representative members of all five genera of the Parvovirinae, and our analyses have revealed a much greater variety or genetic strategies than previously thought. Our work makes clear that members of three of the five parvovirus genera, the Erythrovirus, Amdovirus, and probably Bocavirus groups use only a single promoter in their left hand end, and so regulation of their expression must be exclusively posttranscriptional. Our work has also shown that in addition to the Erythroviruses, members of the Dependovirus, Amdovirus and Bocavirus genera also use alternative polyadenylation at a site within the center of the genome. Thus, alternative internal polyadenylation as a means to govern parvovirus gene expression has emerged as the rule rather than the exception. In addition, it is now clear that the parvoviruses make greater use of alternative translation strategies for their expression than previously appreciated, both for their structural and nonstructural proteins - which is perhaps not surprising, given their need to express complex patterns of gene expression from such compact genomes. Discovery of the variation in parvovirus expression strategies has also underscored the potential importance of a number of proteins not predicted from studies on the prototypes MVM, AAV and B19. For example, the GPV large Rep 1 protein acts as a transcriptional activator of its capsid protein-encoding gene, yet seems to be distinct in its mode of action from either the AAV2 Rep protein or MVM NS1. Additionally, the Bocavirus NP1 protein is abundantly expressed by both bovine parvovirus BPV and the human bocavirus HBoV, suggesting it may be a prototype of parvovirus proteins encoded by an ORF in the center of many parvovirus genomes. In this application we propose to I.) complete the determination of the transcription profiles of representative examples of all the Parvovirinae genera;II. characterize new expression strategies mandated by the newly identified genetic profiles;and III. determine the function of novel parvoviral proteins whose importance these new profiles make clear. These studies will significantly advance our understanding of this important group of viruses, provide a framework for understanding the evolutionary relationships between members of the Parvovirinae, and as has been the case in the past, continue to reveal attractive, tractable models to examine basic cellular functions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI046458-09
Application #
7805585
Study Section
Special Emphasis Panel (ZRG1-IDM-B (02))
Program Officer
Park, Eun-Chung
Project Start
2000-02-01
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
9
Fiscal Year
2010
Total Cost
$424,938
Indirect Cost
Name
University of Missouri-Columbia
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
153890272
City
Columbia
State
MO
Country
United States
Zip Code
65211
Fasina, Olufemi O; Stupps, Stephanie; Figueroa-Cuilan, Wanda et al. (2017) Minute Virus of Canines NP1 Protein Governs the Expression of a Subset of Essential Nonstructural Proteins via Its Role in RNA Processing. J Virol 91:
Majumder, Kinjal; Etingov, Igor; Pintel, David J (2017) Protoparvovirus Interactions with the Cellular DNA Damage Response. Viruses 9:
Mascarenhas, Joaquina X; Korokhov, Nikolay; Burger, Lisa et al. (2017) Genetic engineering of CHO cells for viral resistance to minute virus of mice. Biotechnol Bioeng 114:576-588
Fasina, Olufemi O; Dong, Yanming; Pintel, David J (2016) NP1 Protein of the Bocaparvovirus Minute Virus of Canines Controls Access to the Viral Capsid Genes via Its Role in RNA Processing. J Virol 90:1718-28
Adeyemi, Richard O; Pintel, David J (2014) The ATR signaling pathway is disabled during infection with the parvovirus minute virus of mice. J Virol 88:10189-99
Adeyemi, Richard O; Fuller, Matthew S; Pintel, David J (2014) Efficient parvovirus replication requires CRL4Cdt2-targeted depletion of p21 to prevent its inhibitory interaction with PCNA. PLoS Pathog 10:e1004055
Adeyemi, Richard O; Pintel, David J (2014) Parvovirus-induced depletion of cyclin B1 prevents mitotic entry of infected cells. PLoS Pathog 10:e1003891
Cotmore, Susan F; Agbandje-McKenna, Mavis; Chiorini, John A et al. (2014) The family Parvoviridae. Arch Virol 159:1239-47
Sukhu, Loretta; Fasina, Olufemi; Burger, Lisa et al. (2013) Characterization of the nonstructural proteins of the bocavirus minute virus of canines. J Virol 87:1098-104
Adeyemi, Richard O; Pintel, David J (2012) Replication of minute virus of mice in murine cells is facilitated by virally induced depletion of p21. J Virol 86:8328-32

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