Transient Inhibition of Avian Myeloblastosis Virus Reproduction by Amethopterin and Fluorodeoxyuridine

Abstract

Avian myeloblastosis virus cannot initiate its reproduction in the presence of amethopterin or fluorodeoxyuridine. This inhibition is reversed by thymidine. Addition of either inhibitor after virus production has started does not inhibit further virus synthesis. In presence of either inhibitor, deoxyribonucleic acid synthesis is inhibited by over 90%, but ribonucleic acid synthesis is not affected. Cells resume their normal growth rate 24 hr after removal of either inhibitor.Based upon the effects of inhibitors of deoxyribonucleic acid (DNA) synthesis, the replication of Rous sarcoma virus (RSV), and of its helper Rous-associated virus (RAV), may be divided into two temporal stages: (i) the initiation of virus reproduction which is prevented by inhibitors of DNA synthesis (1, 2, 17) and (ii) stages subsequent to initiation which are not affected by the same inhibitors. Since this property may be unique among certain ribonucleic acid (RNA) viruses, particularly the avian leukosis viruses, it seemed desirable to determine whether early events in the replication of avian myeloblastosis virus (AMV) were affected by inhibitors of DNA synthesis. To this end, we determined whether this phenomenon occurs under rigorous conditions of DNA inhibition in which cells were not irreversibly damaged but were able to resume normal growth after removal of the inhibitors. Under these conditions, the initiation of AMV reproduction was found to be inhibited in the presence of inhibitors of DNA synthesis. Continuation of virus production, however, was not affected.

Incorporation of Precursors into Ribonucleic Acid, Protein, Glycoprotein, and Lipoprotein of Avian Myeloblastosis Virions

“…Fundamental Cancer Res. 22nd Abstr., p. [14][15][16][17]1968). Thus, part of the delay may be accounted for in this manner.…”

“…The production of AMV and of other RNA tumor viruses is arrested by inhibitors of DNA transcription, e.g., actinomycin D (1, 23, 25; Baluda, unpublished data). This finding, coupled with the fact that inhibitors of DNA synthesis prevent the initiation of vimUs production if added during the first 12 hr postinfection, whereas they do not later, suggests that the synthesis of viral RNA is mediated via a DNA template (3,16,23).…”

Carcinogenesis by RNA sarcoma viruses. XIV. Infection of stationary cultures with murine sarcoma virus (harvey)

“…In the present study no distinction has been made between production of MSV and of murine leukemia virus (O'Connor and Fischinger, 1968), as only the focus-forming capacity of the viral harvests was measured. However, Yoshikura (1967) has demonstrated a possible requirement for DNA synthesis for the growth of Friend leukemia virus, and Rous-associated viruses (Bader, 1965) and avian myeloblastosis virus (Knudson et al, 1967) also show a requirement for DNA synthesis in their multiplication. Therefore, the results we have observed can be explained by an inhibition of either the sarcoma component or the leukemia component of the viral stock or both.…”

Transformation by Murine Sarcoma Virus: Fixation (Deoxyribonucleic Acid Synthesis) and Development

“…Reproduction of Rous sarcoma virus requires the synthesis of deoxyribonucleic acid (DNA) during the early stages of infection (1,7,14), and a similar requirement was observed for cellular transformation by Rous sarcoma virus (3). The synthesis of DNA has been implicated in the reproduction of other RNA-containing oncogenic viruses (2,10,20) and may be a requirement in the reproduction of all RNA tumor viruses. In the present studies, a requirement for DNA synthesis in the transformation of cells by MSV is demonstrated.…”