MCDB










molecular basis of host-pathogen interactions in plants
Savithramma Dinesh-Kumar, Ph.D.

Savithramma Dinesh-Kumar, Ph.D.

Associate Professor of Molecular, Cellular & Developmental Biology
Room: KBT 826
Lab number: 29760
Phone: (203) 432-9965
Email: savithramma.dinesh-kumar@yale.edu
Web site

B.S. & M.S. University of Agricultural Sciences, India 1984; Ph.D. Iowa State Univ. 1993

My laboratory is studying host-pathogen interactions and gene silencing using genetic, molecular, biochemical and genomic approaches.

The relationships between eukaryotic viruses and their hosts have evolved over millions of years. To produce disease, viruses must enter the host, multiply locally in host tissues, and spread from the site of entry, all the while overcoming or evading host immune responses. Plants have evolved various anti-viral defense strategies. For example, one strategy involves a plant disease resistance (R) gene product that function as receptors to recognize a specific pathogen-encoded ligand and then to initiate defense responses. Another strategy is virus-induced gene silencing (VIGS) or post-transcriptional gene silencing (PTGS) and it is an adaptive immune response, meaning that a host can recognize viral nucleic acids and customize a sequence-specific response to clear viral infection. At the same time, viruses have evolved counter-defense strategies. For example, viruses disrupt mRNA expression and translation in replicating cells to support viral survival. Some viruses encode proteins that overcome VIGS or PTGS-mediated defense. It is important to understand the molecular mechanisms by which viruses evade the host's antiviral defenses.

R genes that confer resistance to viral, fungal, bacterial, nematode and insect pathogens encode structurally similar proteins. R genes are classified into five groups, the largest one being NBS-LRR (Nucleotide Binding Site-Leucine Rich Repeat) proteins with variable N-terminal domains. Two virus specific R genes that are being studied in my laboratory are N (against tobacco mosaic virus, TMV) and RCY1 (against cucumber mosaic virus, CMV), encode proteins that belongs to NBS-LRR class. These virus specific R proteins have different structures at their amino-termini: N contains a toll-interleukin 1 receptor homology region (TIR), while HRT contains a coiled-coil (CC) domain. Interestingly, the NBS region of R genes shares homology with the NBS region of animal cell death genes including CED4 from C. elegans, and Apaf-1, FLASH, CARD4 and NOD1 from humans. My laboratory is interested in understanding signaling events that lead to N- and HRT-mediated resistance to TMV and CMV respectively.

Recently my laboratory discovered that P58IPK, a cellular inhibitor of the mammalian double stranded RNA activated protein kinase (PKR), plays an important role in viral pathogenesis and cell death in plants. Our results hint at the conservation of the P58IPK pathway in plants and animals. However, the biological significance of this pathway seems to be different in these two systems. In animals, P58IPK is recruited by the influenza virus to limit PKR-mediated innate antiviral response. In plants, P58IPK is required by viruses for virulence and therefore functions as a susceptibility factor. We are continuing studies on P58IPK to determine its involvement in viral pathogenesis.

PTGS or cosuppression is a sequence specific RNA degradation mechanism in plants. It is functionally similar to quelling in Neurospora and RNA interference (RNAi) in vertebrate and invertebrate animal systems. RNA viruses carrying sequences homologous to a transgene or an endogenous gene can be both triggers and targets of PTGS. When a virus vector is engineered to carry host-derived sequences it can be used to silence the cognate endogenous genes. The phenotype of the plant silenced by VIGS for a particular gene mimics the phenotype of loss of function mutant. We have developed a TRV (Tobacco Rattle Virus) vector, which we use very effectively in gene function analysis in Nicotiana, tomato and Arabidopsis.

Selected Publications

*Bilgin, D.D., *Liu, Y., Schiff, M., and Dinesh-Kumar, S.P. (2003). P58IPK, a plant ortholog of double-stranded RNA-dependent protein kinase PKR inhibitor, functions in viral pathogenesis. Developmental Cell 4:651-661.
*Contributed equally to this paper

Takahashi H, Miller J, Nozaki Y, Takeda M, Shah J, Hase S, Ikegami M, Ehara Y, Dinesh-Kumar SP. (2002) RCY1, an Arabidopsis thaliana RPP8/HRT family resistance gene, conferring resistance to cucumber mosaic virus requires salicylic acid, ethylene and a novel signal transduction mechanism. Plant Journal 32:655-667.

Liu, Y., Schiff, M., Serino, G., Deng, X-W., and Dinesh-Kumar, S.P. (2002). Role of SCF ubiquitin-ligase and the COP9 signalosome in the N gene-mediated resistance response to tobacco mosaic virus. Plant Cell 14: 1483-1496.

Dinesh-Kumar, S.P., Tham, Wai-Hong., and Baker, B. (2000). Structure-function analysis of the tobacco mosaic virus resistance gene N. Proceedings of the National Academy of Science. 97:14789-14794.

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