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Defining RNA and Protein Factors Affecting Tombusvirus Replication
Department of Plant Pathology
Viruses cause major losses in agriculture. Replication of viruses in infected hosts is the central part of viral pathogenesis. However, the components of viral replicases and their functions are still elusive. The purpose of this study is to define the multiple functions of the tombusvirus replication proteins, the viral genome and host proteins within the viral replicase complex.
2009 Project Description
The PI attended 5 meetings (one international) and gave 5 talks (4 plenary, invited) presentation. Lab members gave 2 talks at the meeting of the American Society of Virology.
Plus-stranded RNA viruses, which are important pathogens of humans, animals and plants, replicate in the infected cells by assembling viral replicase complexes consisting of viral- and host-coded proteins.
The PI showed that a group of host factors called ESCRT proteins (endosomal sorting complexes required for transport) play important roles in tombusvirus replication. The expression of dominant negative mutants of ESCRT factors inhibited virus replication in the plant host, suggesting that tombusviruses co-opt selected ESCRT proteins for the assembly of the viral replicase complex.
In addition, the authors show direct interaction between the viral p33 replication protein and Vps23p ESCRT-I and Bro1p accessory ESCRT factors. The interaction with p33 leads to the recruitment of Vps23p to the peroxisomes, the sites of tombusvirus replication. The authors also showed that the viral RNA within the viral replicase complex became more sensitive to ribonuclease in the absence of ESCRT factors, suggesting that the protection of the viral RNA is compromised within the replicase complex assembled in the absence of ESCRT proteins. Intriguingly, the host ESCRT factors also affect the budding of several enveloped viruses, intracellular transport of proteins and cytokinesis. Overall, this work demonstrates that a plus-stranded RNA virus uses the endosomal sorting pathway in a unique way.
Barajas D, Jiang Y, Nagy PD (2009) A Unique Role for the Host ESCRT Proteins in Replication of Tomato bushy stunt virus. PLoS Pathog 5: e1000705.
Wang RY, Stork J, Nagy PD (2009) A key role for heat shock protein 70 in the localization and insertion of tombusvirus replication proteins to intracellular membranes. J Virol 83: 3276-3287.
Sasvari, Z., Bach, S., Blondel, M. and Nagy PD (2009) Inhibition of RNA recruitment and replication of an RNA virus by acridine derivatives with known anti-prion activities. PLoS One 4(10), e7376.
Wang, R. Y., Stork, J., Pogany, J., and Nagy PD (2009). A temperature sensitive mutant of heat shock protein 70 reveals an essential role during the early steps of tombusvirus replication. Virology 394, 28-38.
Barajas, D., Li, Z., and Nagy PD (2009). The Nedd4-Type Rsp5p Ubiquitin Ligase Inhibits Tombusvirus Replication by Regulating Degradation of the p92 Replication Protein and Decreasing the Activity of the Tombusvirus Replicase. J Virol 83, 11751-11764.
Wu B, Pogany J, Na H, Nicholson BL, Nagy PD, et al. (2009) A Discontinuous RNA Platform Mediates RNA Virus Replication: Building an Integrated Model for RNA-based Regulation of Viral Processes. PLoS Pathog 5: e1000323.
7. Li Z, Pogany J, Panavas T, Xu K, Esposito AM, et al. (2009) Translation elongation factor 1A is a component of the tombusvirus replicase complex and affects the stability of the p33 replication co-factor. Virology 385: 245-260.
Jaag HM, Nagy PD (2009) Silencing of Nicotiana benthamiana Xrn4p exoribonuclease promotes tombusvirus RNA accumulation and recombination. Virology 386: 344-352.
Pathak, K.B.; Nagy, P.D. (2009) Defective Interfering RNAs: Foes of Viruses and Friends of Virologists. Viruses 1: 895-919.