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Title: Fidelity of a viral RNA polymerase in an intact host: template structure and host factors affect rates of deletion mutations

Author
item PITA, JUSTIN - NOBLE FOUNDATION
item DE MIRANDA, JOACHIM - NOBLE FOUNDATION
item Schneider, William
item ROOSSINCK, MARILYN - NOBLE FOUNDATION

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/15/2007
Publication Date: 11/1/2007
Citation: Pita, J., De Miranda, J., Schneider, W.L., Roossinck, M.J. 2007. Fidelity of a viral RNA polymerase in an intact host: template structure and host factors affect rates of deletion mutations. Journal of Virology. 81:9072-9077.

Interpretive Summary: RNA viruses are known to be incredibly adaptable, making them difficult pathogens to combat. In plant viruses this adaptability often results in the breakdown of host resistance. This adaptability is due in part to high levels of genetic variability in viral populations. It has often been proposed that the high levels of variability are due to mistake prone replication that leads to high numbers of mutations. This paper describes work to determine just how mistake prone the replication system of a plant virus can be, using a model virus called cucumber mosaic virus (CMV). Surprisingly, it was determined that the CMV replication system doesn’t make mutations at a constant rate. Rather, the rate of mutations varies depending on the host and on the genetic sequence of the template RNA that is being replicated. Both of these findings have never been described in any viral system, and they suggest that it may be possible to control the rate of mutations in plant viruses such as CMV. This could lead to novel approaches to combating plant viral diseases.

Technical Abstract: Plant RNA viruses often have very diverse populations. One of the commonly proposed mechanisms for generating these diverse populations is the error prone RNA-dependent RNA polymerase, based on examples from a number of human and bacterial viruses. This paper describes work to determine the insertion/deletion rate for a plant RNA virus: cucumber mosaic virus (CMV). This is the first study of mutation rates in a plant virus, and the first study of viral error rates in an intact plant. Surprisingly, it was determined that the insertion deletion rate was not constant. Rather, it varied between different host species and varied depending on the secondary structure of the template. Both of these findings are novel, and suggest that RNA-dependent RNA polymerase error rate could be controlled and possibly used as an antiviral mechanism.