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Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 1999 Mar 29;354(1383):665–673. doi: 10.1098/rstb.1999.0419

Tobacco mosaic virus and the virescence of biotechnology.

T H Turpen 1
PMCID: PMC1692531  PMID: 10212947

Abstract

There is a growing realization that a modern combination of molecular biology and agriculture will provide a photosynthetic basis for the biosynthesis of an increasing variety of complex and valuable molecules. This 'greening' of biotechnology may impact on the global environment in many beneficial ways, but will perhaps have its most significant impact on human health. In the past decade, the capacity to use plants as an expanded source of therapeutics has grown through the accelerated development of effective viral transfection vectors for gene transfer to cultivated crops. Recombinant vectors based on tobacco mosaic virus (TMV) and other members of the Tobamovirus genus are now used to transfect commercially meaningful quantities of plant biomass cultivated in enclosed greenhouses and multiacre fields. Viral RNA promoters are effectively manipulated for the synthesis of recombinant messenger RNAs in whole plants. Chimeric plant virus and virus-like particles are designed for peptide production and display from recombinant structural protein-gene fusions. Gene functions are assessed and modified by either virus-mediated expression or cytosolic inhibition of expression at the RNA level. Recombinant virus populations, propagated by inoculating plants with infectious RNA transcripts or recombinant virions, have proved to be genetically stable over product-manufacturing cycles. Large volumes of highly purified protein products isolated from transfected foliage conform reproducibly to the specifications required for well-characterized biologics. In some cases, they exceed the specific activities of molecules purified from alternative recombinant and native sources. The resulting products are then formulated according to the developing national regulatory guidelines appropriate for agriculture-based manufacturing. Each of these innovations was first realized by researchers using clones of tobamovirus genes and recombinant genomes. This progress is founded on the heritage of a century of fundamental TMV research.

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Selected References

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  1. Abel P. P., Nelson R. S., De B., Hoffmann N., Rogers S. G., Fraley R. T., Beachy R. N. Delay of disease development in transgenic plants that express the tobacco mosaic virus coat protein gene. Science. 1986 May 9;232(4751):738–743. doi: 10.1126/science.3457472. [DOI] [PubMed] [Google Scholar]
  2. Ahlquist P., French R., Janda M., Loesch-Fries L. S. Multicomponent RNA plant virus infection derived from cloned viral cDNA. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7066–7070. doi: 10.1073/pnas.81.22.7066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brady R. O., Gal A. E., Bradley R. M., Martensson E., Warshaw A. L., Laster L. Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency. N Engl J Med. 1967 May 25;276(21):1163–1167. doi: 10.1056/NEJM196705252762101. [DOI] [PubMed] [Google Scholar]
  4. Calhoun D. H., Bishop D. F., Bernstein H. S., Quinn M., Hantzopoulos P., Desnick R. J. Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7364–7368. doi: 10.1073/pnas.82.21.7364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coppola G., Yan Y., Hantzopoulos P., Segura E., Stroh J. G., Calhoun D. H. Characterization of glycosylated and catalytically active recombinant human alpha-galactosidase A using a baculovirus vector. Gene. 1994 Jul 8;144(2):197–203. doi: 10.1016/0378-1119(94)90378-6. [DOI] [PubMed] [Google Scholar]
  6. Cruz S. S., Chapman S., Roberts A. G., Roberts I. M., Prior D. A., Oparka K. J. Assembly and movement of a plant virus carrying a green fluorescent protein overcoat. Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6286–6290. doi: 10.1073/pnas.93.13.6286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Culver J. N., Stubbs G., Dawson W. O. Structure-function relationship between tobacco mosaic virus coat protein and hypersensitivity in Nicotiana sylvestris. J Mol Biol. 1994 Sep 16;242(2):130–138. doi: 10.1006/jmbi.1994.1564. [DOI] [PubMed] [Google Scholar]
  8. Dawson W. O., Beck D. L., Knorr D. A., Grantham G. L. cDNA cloning of the complete genome of tobacco mosaic virus and production of infectious transcripts. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1832–1836. doi: 10.1073/pnas.83.6.1832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dawson W. O., Lewandowski D. J., Hilf M. E., Bubrick P., Raffo A. J., Shaw J. J., Grantham G. L., Desjardins P. R. A tobacco mosaic virus-hybrid expresses and loses an added gene. Virology. 1989 Sep;172(1):285–292. doi: 10.1016/0042-6822(89)90130-x. [DOI] [PubMed] [Google Scholar]
  10. De Zoeten G. A., Penswick J. R., Horisberger M. A., Ahl P., Schultze M., Hohn T. The expression, localization, and effect of a human interferon in plants. Virology. 1989 Sep;172(1):213–222. doi: 10.1016/0042-6822(89)90123-2. [DOI] [PubMed] [Google Scholar]
  11. Donson J., Kearney C. M., Hilf M. E., Dawson W. O. Systemic expression of a bacterial gene by a tobacco mosaic virus-based vector. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7204–7208. doi: 10.1073/pnas.88.16.7204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. FUNATSU G., FRAENKEL-CONRAT H. LOCATION OF AMINO ACID EXCHANGES IN CHEMICALLY EVOKED MUTANTS OF TOBACCO MOSAIC VIRUS. Biochemistry. 1964 Sep;3:1356–1362. doi: 10.1021/bi00897a028. [DOI] [PubMed] [Google Scholar]
  13. Fitchen J., Beachy R. N., Hein M. B. Plant virus expressing hybrid coat protein with added murine epitope elicits autoantibody response. Vaccine. 1995 Aug;13(12):1051–1057. doi: 10.1016/0264-410x(95)00075-c. [DOI] [PubMed] [Google Scholar]
  14. French R., Janda M., Ahlquist P. Bacterial gene inserted in an engineered RNA virus: efficient expression in monocotyledonous plant cells. Science. 1986 Mar 14;231(4743):1294–1297. doi: 10.1126/science.231.4743.1294. [DOI] [PubMed] [Google Scholar]
  15. GIERER A., MUNDRY K. W. Production of mutants of tobacco mosaic virus by chemical alteration of its ribonucleic acid in vitro. Nature. 1958 Nov 22;182(4647):1457–1458. doi: 10.1038/1821457a0. [DOI] [PubMed] [Google Scholar]
  16. Gallie D. R., Sleat D. E., Watts J. W., Turner P. C., Wilson T. M. The 5'-leader sequence of tobacco mosaic virus RNA enhances the expression of foreign gene transcripts in vitro and in vivo. Nucleic Acids Res. 1987 Apr 24;15(8):3257–3273. doi: 10.1093/nar/15.8.3257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hamamoto H., Sugiyama Y., Nakagawa N., Hashida E., Matsunaga Y., Takemoto S., Watanabe Y., Okada Y. A new tobacco mosaic virus vector and its use for the systemic production of angiotensin-I-converting enzyme inhibitor in transgenic tobacco and tomato. Biotechnology (N Y) 1993 Aug;11(8):930–932. doi: 10.1038/nbt0893-930. [DOI] [PubMed] [Google Scholar]
  18. Jorgensen R. A., Atkinson R. G., Forster R. L., Lucas W. J. An RNA-based information superhighway in plants. Science. 1998 Mar 6;279(5356):1486–1487. doi: 10.1126/science.279.5356.1486. [DOI] [PubMed] [Google Scholar]
  19. Karrer E. E., Beachy R. N., Holt C. A. Cloning of tobacco genes that elicit the hypersensitive response. Plant Mol Biol. 1998 Mar;36(5):681–690. doi: 10.1023/a:1005949304445. [DOI] [PubMed] [Google Scholar]
  20. Kearney C. M., Donson J., Jones G. E., Dawson W. O. Low level of genetic drift in foreign sequences replicating in an RNA virus in plants. Virology. 1993 Jan;192(1):11–17. doi: 10.1006/viro.1993.1002. [DOI] [PubMed] [Google Scholar]
  21. Kumagai M. H., Donson J., della-Cioppa G., Harvey D., Hanley K., Grill L. K. Cytoplasmic inhibition of carotenoid biosynthesis with virus-derived RNA. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1679–1683. doi: 10.1073/pnas.92.5.1679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kumagai M. H., Keller Y., Bouvier F., Clary D., Camara B. Functional integration of non-native carotenoids into chloroplasts by viral-derived expression of capsanthin-capsorubin synthase in Nicotiana benthamiana. Plant J. 1998 May;14(3):305–315. doi: 10.1046/j.1365-313x.1998.00128.x. [DOI] [PubMed] [Google Scholar]
  23. Kumagai M. H., Turpen T. H., Weinzettl N., della-Cioppa G., Turpen A. M., Donson J., Hilf M. E., Grantham G. L., Dawson W. O., Chow T. P. Rapid, high-level expression of biologically active alpha-trichosanthin in transfected plants by an RNA viral vector. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):427–430. doi: 10.1073/pnas.90.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lindbo J. A., Silva-Rosales L., Proebsting W. M., Dougherty W. G. Induction of a Highly Specific Antiviral State in Transgenic Plants: Implications for Regulation of Gene Expression and Virus Resistance. Plant Cell. 1993 Dec;5(12):1749–1759. doi: 10.1105/tpc.5.12.1749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Meshi T., Ishikawa M., Motoyoshi F., Semba K., Okada Y. In vitro transcription of infectious RNAs from full-length cDNAs of tobacco mosaic virus. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5043–5047. doi: 10.1073/pnas.83.14.5043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Modelska A., Dietzschold B., Sleysh N., Fu Z. F., Steplewski K., Hooper D. C., Koprowski H., Yusibov V. Immunization against rabies with plant-derived antigen. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2481–2485. doi: 10.1073/pnas.95.5.2481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Namba K., Pattanayek R., Stubbs G. Visualization of protein-nucleic acid interactions in a virus. Refined structure of intact tobacco mosaic virus at 2.9 A resolution by X-ray fiber diffraction. J Mol Biol. 1989 Jul 20;208(2):307–325. doi: 10.1016/0022-2836(89)90391-4. [DOI] [PubMed] [Google Scholar]
  28. Porta C., Spall V. E., Loveland J., Johnson J. E., Barker P. J., Lomonossoff G. P. Development of cowpea mosaic virus as a high-yielding system for the presentation of foreign peptides. Virology. 1994 Aug 1;202(2):949–955. doi: 10.1006/viro.1994.1417. [DOI] [PubMed] [Google Scholar]
  29. Ryan M. D., King A. M., Thomas G. P. Cleavage of foot-and-mouth disease virus polyprotein is mediated by residues located within a 19 amino acid sequence. J Gen Virol. 1991 Nov;72(Pt 11):2727–2732. doi: 10.1099/0022-1317-72-11-2727. [DOI] [PubMed] [Google Scholar]
  30. Scholthof H. B., Scholthof K. B., Jackson A. O. Plant virus gene vectors for transient expression of foreign proteins in plants. Annu Rev Phytopathol. 1996;34:299–323. doi: 10.1146/annurev.phyto.34.1.299. [DOI] [PubMed] [Google Scholar]
  31. Skuzeski J. M., Nichols L. M., Gesteland R. F., Atkins J. F. The signal for a leaky UAG stop codon in several plant viruses includes the two downstream codons. J Mol Biol. 1991 Mar 20;218(2):365–373. doi: 10.1016/0022-2836(91)90718-l. [DOI] [PubMed] [Google Scholar]
  32. Takamatsu N., Ishikawa M., Meshi T., Okada Y. Expression of bacterial chloramphenicol acetyltransferase gene in tobacco plants mediated by TMV-RNA. EMBO J. 1987 Feb;6(2):307–311. doi: 10.1002/j.1460-2075.1987.tb04755.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Turpen T. H., Reinl S. J., Charoenvit Y., Hoffman S. L., Fallarme V., Grill L. K. Malarial epitopes expressed on the surface of recombinant tobacco mosaic virus. Biotechnology (N Y) 1995 Jan;13(1):53–57. doi: 10.1038/nbt0195-53. [DOI] [PubMed] [Google Scholar]
  34. Turpen T. Molecular cloning of a potato virus Y genome: nucleotide sequence homology in non-coding regions of potyviruses. J Gen Virol. 1989 Aug;70(Pt 8):1951–1960. doi: 10.1099/0022-1317-70-8-1951. [DOI] [PubMed] [Google Scholar]
  35. Turpen T, Garger S J, Marks M D, Grill L K. Molecular cloning and physical characterization of a Brassica linear mitochondrial plasmid. Mol Gen Genet. 1987 Sep;209(2):227–233. doi: 10.1007/BF00329647. [DOI] [PubMed] [Google Scholar]
  36. Wilson T. M. Plant viruses: a tool-box for genetic engineering and crop protection. Bioessays. 1989 Jun;10(6):179–186. doi: 10.1002/bies.950100602. [DOI] [PubMed] [Google Scholar]
  37. Yusibov V., Modelska A., Steplewski K., Agadjanyan M., Weiner D., Hooper D. C., Koprowski H. Antigens produced in plants by infection with chimeric plant viruses immunize against rabies virus and HIV-1. Proc Natl Acad Sci U S A. 1997 May 27;94(11):5784–5788. doi: 10.1073/pnas.94.11.5784. [DOI] [PMC free article] [PubMed] [Google Scholar]

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