RNA tumor viruses

This enzyme is associated with the virions of RNA tumor viruses such as the Rous sarcoma virus (RSV). The enzyme has remarkable enzymatic activity in that it can catalyze several seemingly diverse steps in the synthesis of double-stranded DNA from the single-stranded RNA viral genome. The enzyme uses a tRNA for tryp-tophan as a primer to make a copy of DNA that is complementary to the viral RNA. The resulting RNA-DNA hybrid is converted to a double-stranded DNA molecule by ribon-uclease (RNase)H and DNA-dependent DNA polymerase activities that are intrinsic to reverse transcriptase. 

Vidarabine (adenine arabinoside, Vira-A) is an adenine nucleoside analogue containing arabinose in place of ri-bose. It is obtained from cultures of Streptomyces an-tibioticus and has activity against HSV-1, HSV-2, VZV, CMV, HBV, poxviruses, hepadnaviruses, rhabdoviruses, and certain RNA tumor viruses. 

Price, P.J. Mishra, N.K. (1980) The use of Fischer rat embryo cells as a screen for chemical carcinogens and the role of the nontransforming type C RNA tumor viruses in the assay. Adv. mod. environ. Toxicol.. 1. 213-239... 

Retroviruses have featured prominently in recent advances in the molecular understanding of cancer. Most retroviruses do not kill their host cells but remain integrated in the cellular DNA, replicating when the cell divides. Some retroviruses, classified as RNA tumor viruses, contain an oncogene that can cause the cell to grow abnormally (see Fig. 12-47). The first retrovirus of this type to be studied was the Rous sarcoma virus (also called avian sarcoma virus Fig. 26-31), named for F. Peyton Rous, who studied chicken tumors now known to be caused by this virus. Since the initial discovery of oncogenes by Flarold Varmus and Michael Bishop, many dozens of such genes have been found in retroviruses. 

Reverse transcriptase RNA tumor viruses, e.g., avian myoblastosis virus 5 —> 3 DNA chain growth... 

RNA tumor viruses (retroviruses) that infect animal cells exhibit a different replication strategy. In their virions they carry an enzyme that uses the viral RNA as a template to synthesize a DNA copy (see chapters 26 and 27). This DNA becomes integrated into the host genome. Subsequently the viral RNA is transcribed from the integrated viral DNA using host cell RNA polymerase. 

Information transfer in biological systems usually involves transfer from DNA to DNA (DNA replication), DNA to RNA (transcription) and RNA to protein (translation). Most RNA viruses have an additional mode of passing information RNA to RNA (RNA replication). RNA tumor viruses have yet another additional way of passing information RNA to DNA (reverse transcription). 

Synthetic polymers containing either deoxyribonucleotide or ribonucleotide strands can be used as templates by the DNA polymerases of RNA tumor viruses. Table 12 shows the activity of distamycin/A and its amino acid derivatives on the DNA polymerase reaction of FL-virions, catalyzed by poly rA ... 

Table 16. Inhibition of reverse-transcriptase activity of RNA tumor viruses by daunomycin derivatives. Figures in brackets are percentages...

The results show that the inhibition exerted by daunomycin derivatives against DNA polymerase from RNA tumor viruses is selectively dependent on... 

Synthetic polymers containing either desoxyribonucleotide or ribonucleotide strands are known to stimulate the in vitro DNA synthesis by RNA tumor viruses. Some inhibitors of the DNA-polymerase reaction in RNA tumor viruses are known to exhibit a template-primer specificity6, 7 34 Table 22 shows the inhibition of template-dependent DNA polymerase activity of FLV by DEAE-F at various concentrations. The reaction catalyzed by poly (dl - dC) is most strongly stimulated by DEAE-F. Thus at 20 pg/reaction mixt. of DEAE-F the incorporation of 3H—dGMP is almost 4 times that of control. 

The present results show that the inhibition exerted by DEAE-F against DNA polymerases from RNA tumor viruses is uniquely and selectively dependent on the type of primer-template used in the assay system. The wide differences between the inhibitory concentrations of DNA-dependent enzymatic... 

Soon after the discovery of DNA polymerases in virions of RNA tumor viruses, a great deal of hope was expressed that the discovery might lead to resolve the possibility of the involvement of oncorna viruses in an inapparent form in spontaneous or chemically induced tumors, especially in man. So far, there has been some evidence in support that RNA tumor viruses are related to human neoplasia. 

Panet, A., Baltimore, D., and Hanafusa, T. (1975) Quantitation of avian RNA tumor virus reverse transcriptase by radioimmunoassay. J. Virol. 16,146-152. 

The fourth phase of viral oncology has seen the emergence of the revolutionary concept that RNA tumor viruses (oncornaviruses), like their DNA counterparts, contribute genetic information that becomes part of the genome of the affected host cell. With the latest development in viral oncology, tumor viruses have come to be considered more endogenous than exogenous to the hosts. 

T2. Temin, H. M On the Origin of RNA Tumor Viruses, Vol. 69, pp. 173-176. Cold Spring Harbor Lab. Cold Spring Harbor, New York, 1975. 

KAKIUCHI, N., HATTORl, M., NAMBA, T., NISHIZAWA, M., YAMAGISHI, T., OKUDA, T., Inhibitory effect of tannins on reverse transcriptase from RNA tumor virus, J. Nat. Prod., 1985, 48, 614-621. 

Kakiuchi, N. Hattori, M. Namba, T. Nishizawa, M. Yamagishi, T. Okuda, T. Inhibitory Effects of Tannins on Reverse Transcriptase from RNA Tumor Virus. J. Nat. Prod. 1985, 48, 614-621. 

Maytansine s ansa macrolide structure shows noteworthy similarities to those of the rifamycins [255], streptovaricins [256], tolypomycins [257], and geldanamycin [258]. The ansamycin antibiotics and their derivatives have aroused considerable interest as antiviral and antimicrobial agents, and as inhibitors of RNA tumor virus reverse transcriptases. 

Yes, the incorporation of nucleoside triphosphates into an acid-insoluble form is indicative of the presence of a polymerase. The polymerase is likely a DNA polymerase because dNTPs, and not NTPs, were used to form product. Further evidence for a DNA polymerase was that the radiolabeled product was destroyed by a nuclease, DNase, specific for hydrolyzing DNA, and not by one specific for RNA hydrolysis. Additionally, NaOH, which destroys RNA but not DNA, did not destroy the radiolabeled product. Pretreatment of the extract with the two hydrolytic enzymes demonstrated that the enzyme depends on an RNA and not a DNA template for its activity. Thus, this enzyme is an RNA-dependent DNA polymerase. No such enzyme had been observed previously in a cell, and this demonstration, along with similar findings by Howard Temin, of its existence in an RNA tumor virus caused a revision of Francis Crick s central dogma of molecular biology, which stated that information flowed from DNA to RNA to proteins. The demonstration of this RNA-dependent DNA polymerase suggested that in some cases information could flow from RNA to DNA. (This question was derived from D. Baltimore. Viral RNA-dependent DNA polymerase. Nature 226 [1971]1209-1213.)... 

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