Grants and Contracts Details
Description
Replication is the central step in the infectious cycles of plus-stranded RNA viruses,
which cause many devastating diseases in plants, animals and humans. These viruses
replicate inside the infected cells by co-opting an unknown number of host proteins
and reprogramming several cellular pathways. In spite of the significance of host proteins
in viral pathogenesis, our current knowledge on host factors subverted for virus replication is
incomplete.
In order to advance our understanding of the key role of host factors in viral replication,
the PI has recently developed a powerful yeast-based replication system for tombusviruses
(Tomato bushy stunt virus, TBSV), which are plant viruses widespread in crops and aquatic
environments. Recent genome-wide genomics and proteomics screens by the PI led to the
identification of 250 host genes affecting TBSV replication/recombination, demonstrating the
complex nature of host-virus interactions. Altogether, the availability of in vitro replication
systems and development of yeast for efficient replication of the TBSV RNA in
combination with large datasets from genomics and proteomics screens from the PI..s
lab makes tombusviruses the best suited to study host factors involved in viral RNA
replication.
This proposal is aimed at addressing the role of the multifunctional translation
elongation factor 1A (eEF1A), which is a permanent resident in the viral replicase complex
and plays a key role in TBSV replication. Since eEF1A likely affects replication of a large
number of plant and animal viruses, major progress with tombusviruses would be highly
advantageous to other viruses as well. Altogether, characterization of the multiple functions
performed by eEF1A in virus replication will lead to better understanding of the replication
process and development of novel antiviral strategies.
Intellectual merit of the proposal: Pioneering work by the PI will contribute key knowledge to
understanding how host factors participate in viral pathogenesis. The work will unravel the
functions of eEF1A, which have been implicated in replication of a large number of viruses.
The proposed innovative approaches including yeast and plant assays developed for
tombusviruses as well as the powerful cell-free TBSV replication assay in yeast extracts will
likely lead to major new insights into virus replication and viral pathogenesis and will have a
considerable impact on our understanding of the mechanism that transforms the host cells
into “viral factories”.
Broader impacts of the proposed activity: Pioneering research on tombusvirus replication
could immensely help other scientists working with less tractable, but devastating viral
pathogens for which similar studies are currently not yet feasible. Dissection of the role of
eEF1A in viral pathogenesis and disease development will facilitate future antiviral
approaches and treatments to reduce the effect of viral diseases. Education component: High
school and undergraduate students are currently actively participating in research in the PI..s
laboratory, which led to research papers. They are exposed to highly innovative research and
this experience provides them an invaluable learning experience. This research will promote
interdisciplinary (plant pathology, biochemistry, cell biology, genetics) learning. The research
holds promise of benefiting society by leading to groundbreaking results in the area of virus
replication and pathogenesis.
Status | Finished |
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Effective start/end date | 1/15/12 → 12/31/15 |
Funding
- National Science Foundation: $806,796.00
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