Viruses are widely distributed throughout the Kingdom Fungi, including fungi pathogenic to animals and plants. Fungal infections continue to have a significant impact on human health and well-being. Similar to viruses of animals and plants, mycoviruses have potential utility for elucidating host biological processes and manipulating host phenotype. Progress in developing this potential is best illustrated by recent studies with members of the RNA virus family Hypoviridae. Hypoviruses persistently alter phenotypic traits, modulate gene expression and attenuate virulence of their fungal hosts. They are also the only symptomatic mycoviruses for which a reverse genetics system has been developed. Consequently, hypoviruses provide utility as biological control agents and as unique tools for identifying fungal virulence determinants and designing antimycotic therapeutic strategies. Substantial progress has been made in mapping hypovirus-encoded modifiers of cellular signaling pathways and in the characterization of previously mapped viral symptom determinants. Experimental approaches for unraveling hypovirus polyprotein processing pathways have been validated. The development of a host cDNA microarray platform has allowed the monitoring of global transcriptional responses to hypovirus infection. A hypovirus protein was shown to function as a suppressor of RNA silencing in a well characterized heterologous system. Three new Specific Aims have been designed to capture the full advantage of these recent advances and newly developed experimental approaches for further understanding and exploitation of hypovirus molecular biology while meeting the criteria of feasibility, relevance to ongoing studies and general significance: 1) further elucidate the ORFB polyprotein processing pathway, 2) investigate hypovirus-mediated reprogramming of host gene expression by comparing global cellular transcriptional responses to hypovirus infection and to modulation of G-protein/ cAMP signaling and 3) test the fundamental hypothesis that RNA silencing in fungi evolved as an antiviral defense mechanism. The results derived from completion of these coordinated specific aims will have immediate relevance to ongoing efforts to further enhance the utility of hypoviruses and other potentially efficacious RNA viruses for purposes of manipulating their hosts in novel and productive ways.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM055981-10
Application #
7052120
Study Section
Special Emphasis Panel (ZRG1-IDM-L (90))
Program Officer
Basavappa, Ravi
Project Start
1997-05-01
Project End
2009-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
10
Fiscal Year
2006
Total Cost
$325,505
Indirect Cost
Name
University of MD Biotechnology Institute
Department
Type
Organized Research Units
DUNS #
603819210
City
Baltimore
State
MD
Country
United States
Zip Code
21202
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Chen, Min-Mei; Jiang, Mingguo; Shang, Jinjie et al. (2011) CYP1, a hypovirus-regulated cyclophilin, is required for virulence in the chestnut blight fungus. Mol Plant Pathol 12:239-46
Chen, Chen; Sun, Qihong; Narayanan, Buvaneswari et al. (2010) Structure of oxalacetate acetylhydrolase, a virulence factor of the chestnut blight fungus. J Biol Chem 285:26685-96