Milestones in the research on tobacco mosaic virus

Beijerinck's (1898) recognition that the cause of tobacco mosaic disease wa s a novel kind of pathogen became the breakthrough which eventually led 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 t he 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 prote in, and X-ray diffraction analysis of their structure was the first of a he lical nucleoprotein. In the molecular biological phase of research, TMV RNA was the first plant virus genome to be sequenced completely, its genes wer e found to be expressed by cotranslational particle disassembly and the use of subgenomic mRNA, and the mechanism of assembly of progeny particles fro m their separate parts was discovered. Molecular genetical and cell biologi cal techniques were then used to clarify the roles and modes of action of t he TMV non-structural proteins: the 126 kDa and 183 kDa replicase component s and the 30 kDa cell-to-cell movement protein. Three different TMV genes w ere found to act as avirulence genes, eliciting hypersensitive responses co ntrolled by specific, but different, plant genes. One of these (the N gene) was the first plant gene controlling virus resistance to be isolated and s equenced. In the biotechnological sphere, TMV has found several application s: as the first source of transgene sequences conferring virus resistance, in vaccines consisting of TMV particles genetically engineered to carry for eign 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 decrease d the need for such properties, and TMV may have a less dominant role in th e future, it continues to occupy a prominent position in both fundamental a nd applied research.