SEP 13, 2017 9:00 AM PDT

Insights into virus replication: the role of co-opted host proteins and lipids

Speaker
  • Professor, Department of Plant Pathology, University of Kentucky
    Biography
      PETER D. NAGY is a professor at the department of Plant Pathology, University of Kentucky, Lexington, USA. He is an expert on molecular biology of plant viruses; virus replication and recombination, biochemistry and cell biology of plant viruses. Based on systems biology approaches and using yeast and viruses, his laboratory is involved in dissecting the roles of host factors in plant virus infections.
      His work has been supported by grants from National Science Foundation, National Institute of Health and Kentucky Science Foundation. The main research projects are:
      1. Development of the Tomato bushy stunt virus (TBSV)-yeast system to study virus replication and virus-host interactions. His lab has developed the TBSV-yeast system because of the advantages of using yeast as a model host. 2. Genome-wide screens and global proteomics approaches to identify host factors affecting TBSV replication. His lab have performed a dozen complementary genome-wide and global proteomics approaches that have led to the identification of ~500 host genes affecting TBSV replication in yeast. 3. Characterization of co-opted host factors critical for TBSV replication. 4. Discovery of cell-intrinsic restriction factors against TBSV replication.
      Dr. Nagy published 150 scientific papers and got numerous awards for his scientific work, including Science and Engineering Award from the Governor of Kentucky (2002), Faculty Futures Award, University of Kentucky (2004), Bobby Pass Excellence in Grantsmanship Award (2006 and 2013), Thomas P. Cooper Research Award (2007), University Research Professor Award (2007), Ruth Allen Research Award, Phytopathology Society (2008), and prestigious paper award, University of Kentucky (2016).

    Abstract

    Virus – host interactions are currently among the most intensively studied research areas due to the promising new antiviral approaches emerging from these studies. Indeed, RNA viruses, which are important and emerging human, animal and plant pathogens, exploit host cells by recruiting host factors and escaping host antiviral responses. RNA viruses induce the deformation of cellular membrane structures to build extensive viral replication organelles. Approaches interfering with virus replication could be key to limit the significant harm caused by viruses to human health and major losses in agriculture. We study tombusviruses, which are small RNA viruses, as model plant viruses to study virus replication and virus - host interactions using yeast (Saccharomyces cerevisiae) as a surrogate host. Since viruses are intracellular parasites that use the ample resources of eukaryotic cells, it is feasible to study virus replication in model eukaryotic yeast cells. Several systematic genome-wide screens and global proteomic and lipidomic approaches have led to the identification of ~500 host proteins/genes that are implicated in TBSV replication. We characterized the role of 30 co-opted host proteins, sterols and phospholipids in tombusvirus replication. Finally, we also show evidence that tombusviruses usurp the glycolytic (metabolic) pathway to obtain energy to build the extensive virus replication organelles. Altogether, this virus-host system allows for rapid discovery of novel cellular factors affecting plant virus replication. This advance could immensely help other scientists working with less tractable, but devastating viral pathogens for which similar studies are currently more difficult to conduct. 


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