The Contribution of Tobacco Mosaic Virus to Biology and Medicine
- Tobacco mosaic virus has contributed greatly to our understanding of not only the plant viruses and their effects in plants, but also of the viruses of humans and animals and, furthermore, of the structure and function of the genetic code in all organisms.
Some of the “firsts” learned from the study of TMV are mentioned briefly here:
- When Adolph Mayer began to study the tobacco mosaic disease in 1886, it was the first time that a disease was shown to be caused by a fluid free of any of the known pathogenic fungal and bacterial microbes.
- Then, in 1898, Beijerinck proposed that tobacco mosaic was caused by an infectious fluid, which he called a virus, free of any cellular microbe, and this changed the prevailing thinking at the time that microbes had to be cellular.
- TMV was the first virus to be shown (Beale, 1928) that plants infected with it contained a specific antigen.
- It was also the first virus that was quantified (Holmes, 1929) by the number of local lesions produced on healthy leaves by different concentrations of sap of an infected plant, although no one had any idea yet what TMV was.
- Then, in 1935, TMV was the first virus to be isolated in crystal form and to be reported by W. Stanley to consist of an “autocatalytic protein.”
- The following year, 1936, Bowden and Pirie made the small but extremely important correction that TMV actually consisted mostly (95%) of protein but it also contained a small amount (5%) of ribonucleic acid (RNA).
- These discoveries on TMV marked the beginning of virology because, subsequently, methodologies developed to study TMV began to be applied to the study of viruses affecting humans and animals and also microbes such as bacteria.
- Nevertheless, TMV studies continued to lead the way. In 1939, Kausche took the first electron microscope photographs of TMV, giving the first solid evidence of what a virus looks like.
- Then, in the mid-1950s, Gierer and Schramm (1956) and Fraenkel-Conrat (1955), again working with TMV, demonstrated that the nucleic acid (RNA) was responsible for causing infection, whereas the protein surrounded the RNA and merely protected the RNA.
- In 1960, the TMV coat protein was the first virus coat protein to be fully sequenced into its 158 amino acids (Anderer, 1960; Tsugita, 1960), and the sequence of the amino acids of several natural and artificially induced mutant TMV strains was instrumental in establishing the universality of the genetic code and the chemical basis of mutation.
- In 1969, Takebe used TMV for the infection of suspended tobacco leaf protoplasts, thereby providing the basis for a synchronous infection system for studying virus replication.
- TMV was also the first plant RNA virus of which the complete genome was sequenced (Goelet, 1982) and also to which monoclonal antibodies were produced (1982).
- More recently, TMV was the first plant virus to be shown (Powell-Abel, 1986; Beachy, 1986) that introduction and expression of its coat protein gene in plants protected those plants agains TMV.
- In 1987, it was shown that most or all of the TMV coat protein gene can be replaced with a foreign gene and, following inoculation into a plant, the foreign gene is expressed and, if appropriate, may increase the resistance of the plant to disease or may produce vaccines or pharmaceuticals that can be used for the control of human and animal diseases.