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This Nobel Lecture by David Baltimore explores his research on the genetic systems of RNA viruses, focusing on picornaviruses and retroviruses. the discovery of viral RNA-dependent RNA synthesis in picornaviruses, the identification of viral RNA as the messenger RNA for viral proteins, and the revelation of retroviruses as the only RNA viruses known to cause cancer.
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216 Physiology or Medicine 1975
218 Physiology or Medicine 1975
Viruses, Polymerase and Cancer 219
Viruses, Polymerase and Cancer^221
Figure 2. The life cycle of an RNA tumor virus. Based on present knowledge (42), the life cycle of an RNA tumor virus can be separated into two parts. In the first part the virion attaches to the cell and somehow allows its RNA along with reverse transcriptase to get into the cell’s cytoplasm. There the reverse transcriptase causes the synthesis of a DNA copy of the viral RNA. A fraction of the DNA can be recovered as closed, circular DNA (43) and it is presumably that form. which integrates into the cellular DNA. Once the proviral DNA is integrated into cellu- lar DNA it can then be expressed by the normal process of transcription. The two types of product which have been characterized are new virion RNA and messenger RNA. Much of the messenger RNA which specifies the sequence of viral protein is of the same length as the virion RNA but there may also be shorter messenger RNA’s (48). The vi- rus-specific proteins have 2 known functions: one is the transformation of cells which occurs when, for instance, a sarcoma virus infects a fibroblast, the second is to provide the protein for new virion production. The transforming protein is shown here as acting at the cell surface but that is only a hypothesis.
222 Physiology or Medicine 1975
224 Physiology or Medicine 1975
and Bang, F. B. Eds. (Academic Press, New York and London, 1972), pp. 295-
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Baltimore, D. and Franklin, R. M., Proc. Nat. Acad. Sci. U.S.A. 48. 1383 (1962). Franklin, R. M. and Baltimore, D., Cold Spring Harbor Symp. Quant. Biol. 27, 175 (1962).
Baltimore, D. and Franklin, R. M. Biochem. Biophys. Res. Commun. 9, 388, (1962). Baltimore, D. and Franklin, R. M. 1. Biol. Chem. 238, 3395 (1963). Bal- timore, D., Franklin, R. M., Eggers, H. J. and Tamm, I. Proc. Nat. Acad. Sci. U.S.A. 49, 843 (1963). Baltimore, D. and Franklin, R. M., Cold Spring Harbor Symp. Quant. Biol. 28, 105 (1963).
Baltimore, D., Proc. Nut. Acad. Sci. U.S.A. 51, 450 (1964).
Baltimore, D., in The Biochemistry of Viruses, Levy, H. B., Ed., (Marcel Dekker Inc., New York, 1969), pp. 101-l 76.
Levintow, L., in Comprehensive Virology, vol. 2. Fraenkel-Conrat, H. and Wagner, R. R., Eds. (Plenum Press, New York, 1974), pp. 109-169.
Lundquist, R. E., Ehrenfeld, E. and Maizel, J. E., Proc. Nat. Acad. Sci. U.S.A. 71, 4773 (1974).
Baltimore, D., Becker, Y. and Darnell, J. E., Science 143, 1034 (1964). Baltimore, D., J. Mol. Biol. 18, 421 (1966). Baltimore, D., Girard, M. and Darnell, J., Viral- ogy 29, 179 (1966). Baltimore, D. and Girard, M., Proc. Nat. Acad. Sci. U.S.A. 56, 741 (1966). Girard, M., Baltimore, D. and Darnell, J. E., J. Mol. Biol. 24, 59 (1967). Baltimore, D., J, Mol. Biol. 32, 359 (1968).
Girard, M., J. Virol. 3, 376 (1969).
Jacobson, M. F. and Baltimore, D., J. Mol. Biol. 33, 369 (1968).
Jacobson, M. F. and Baltimore, D., Proc. Nat. Acad. Sci. U.S.A.^ 61,^77 (1968). Jacobson, M. F., Asso, J. and Baltimore, D., J. Mol. Biol. 49, 657 (1970).
Viruses, Polymerase and Cancer 225
(Cold Spring Harbor Laboratory, New York, 1973). Bishop, J. M. and Varmus, H. E., in Cancer, vol. 2, Becker, F. F., Ed., (Plenum Press, New York, 1975), pp. 3 - 4 8.
43. Varmus, H. E., Guntaka, R. V., Fan, W. J. W., Heasley, S. and Bishop, J. M., Proc. Nat. Acad. Sci. U.S.A. 71, 3874 (1974). Gianni, A. M., Smotkin, D. and Wein- berg, R. A., Proc. Nat. Acad. Sci. U.S.A. 72, 447 (1975).