‘ Molecular and Cellular Radiobiology Project Title: Storage and Transfer of the Genetic Message 17, Expected Results in FY 1974: (Cont'd.) RX-03-02-(d) interactions warrants, they will be extended by fractionating histones and then studying the interaction of polynucleotides with arginine-rich and lysine-rich histone fractions, The biological effectiveness of such complexes, characterized here by physico-chemical studies, including temperature-melting profile (TM) and resistance to ribonuclease, will be assayed against SFV infection in mice here and in collaboration with Dr, Dr. Southam, Also in collaboration with Southam the effects of polynucleotides will be tested topically against HSV and type 2 given intravaginally in mice, This produces an acute and chronic vaginitis, and the possible oncogenic role of this virus will be explored with and without polynucleotides and other possible enhancing or diminishing agents. A ’ If opportunity permits, the U.5, Department of Agriculture, Veterinary Sciences Research Division, Denver, have indicated an interest in studying the effects of polynucleotide complexes prepared here against VEE virus infection in small animals, Similarly, when collaborators are ready, studies will be resumed on the effects of polynucleotide complexes on FMDV in large animals, e.g. cattle, goats amd sheep, to include the effects of multiple rather than single doses of the complex, a comparison of routes of administration, etc, These studies will be carried out in the carrier State, i,e, in animals that have the virus without necessarily manifesting the disease clinically, in collaboration with Drs. M. Brugh and H, Bahnemann (Pan American Health Organization--WHO--Foot-and-Mouth Disease Center, Rio de Janeiro), The carrier-state animals in Rio have a considerable advantage over experimentally induced disease in large animals at Plum Island because of the considerable heterogeneity in the response of large animals infected experimentally. - The carrier animals already have the virus; moreover the smaller size of Brazilian carrier cattle, and other animals, would conserve the use of synthetic complexes, The studies aimed at elucidating the effects and mechanism of action of polynucleotides in vitro will be extended, These include the enhancement by polynucleotides of lymphocyte transformation in response to specific antigenic stimulation and the inhibition of DNA synthesis by polynucleotides in synchronized HeLa cells. Also,collaboration with Dr, E. Popenoe will continue on the biological significance of RNA-dependent DNA polymerase in HeLa immune cells, These and other in vitro studies will aim toward undes@™ga@nding how polynucleotides and other interferon inducers work. * Th Be do tT 18. Expected Results in FY 1975: Studies described above will continue with directions determined by the findings from current research. (See Continuation Sheet) -y4193ts RX- 258