Beijerinck's (1898) recognition that the cause of tobacco mosaic disease was a novel kind of pathogen became the breakthrough which led eventually to the establishment of virology as a science. Research on this agent, tobacco mosaic virus (TMV), has continued to be at the forefront of virology for the past century.
After an initial phase, in which numerous biological properties of TMV were discovered, its particles were the first shown to consist of RNA and protein, and X–ray diffraction analysis of their structure was the first of a helical nucleoprotein. In the molecular biological phase of research, TMV RNA was the first plant virus genome to be sequenced completely, its genes were found to be expressed by cotranslational particle disassembly and the use of subgenomic mRNA, and the mechanism of assembly of progeny particles from their separate parts was discovered. Molecular genetical and cell biological techniques were then used to clarify the roles and modes of action of the TMV non–structural proteins: the 126 kDa and 183 kDa replicase components and the 30 kDa cell–to–cell movement protein. Three different TMV genes were found to act as avirulence genes, eliciting hypersensitive responses controlled by specific, but different, plant genes. One of these (the
N
gene) was the first plant gene controlling virus resistance to be isolated and sequenced. In the biotechnological sphere, TMV has found several applications: as the first source of transgene sequences conferring virus resistance, in vaccines consisting of TMV particles genetically engineered to carry foreign epitopes, and in systems for expressing foreign genes.
TMV owes much of its popularity as a research model to the great stability and high yield of its particles. Although modern methods have much decreased the need for such properties, and TMV may have a less dominant role in the future, it continues to occupy a prominent position in both fundamental and applied research.
Milestones in research on tobacco mosaic virus