Effects of Polyadenylic Acids on Functions of Murine RNA Tumor Viruses

Abstract

Single-stranded polyribonucleotides, which competitively inhibit murine RNA tumor virus reverse transcriptase in vitro, were tested as inhibitors of various virus functions in cell culture. The compounds had two concentration-dependent effects. At high concentrations (100 gg/ml), both poly(adenylic acid) [poly(A) ] and poly(2'-O-methyladenylic acid) [poly(Am)] inhibited the uptake of radioactively labeled leukemia virus by Swiss mouse embryo cells, but neither had a similar effect on Sindbis virus adsorption. At low concentrations (10 sg/ml), poly(Am) did not inhibit the uptake of leukemia virus but did inhibit virus replication by 85%; in contrast, the replication of Sendai virus and Sindbis virus was not inhibited significantly at this concentration. Both compounds were effective only when added prior to or early during virus infection. Poly(Am) was a much more effective inhibitor than poly(A), probably due to the nuclease resistance of the former compound. Poly(Am) at 5 jsg/ml also inhibited transformation of 3T3 cells by Moloney sarcoma virus. However, neither poly(A) nor poly(Am) at high concentrations inhibited the activation of endogenous leukemia virus by iododeoxyuridine in AKR mouse embryo cells. These results suggest that virus reverse transcriptase plays an essential role in both the replication of exogenous murine leukemia viruses and the transformation of cells by murine sarcoma viruses but probably has no role in the activation of endogenous leukemia virus.

Evidence for a Stable Intermediate in Leukemia Virus Activation in AKR Mouse Embryo Cells

“…These data therefore suggest that the second requirement may be related to a regulatory event governing virus expression, which may be similar or identical to that observed with exogenous virus infection; and it is possible that the physical state of the provirus is identical to that of the activation intermediate. (21,23). These polymers block infection of cells by exogenous virus, apparently by inhibition of the reverse transcriptase reaction (21,22).…”

“…(21,23). These polymers block infection of cells by exogenous virus, apparently by inhibition of the reverse transcriptase reaction (21,22). We examined the effect of poly(Am) added at various times during infection and activation.…”

Inhibition of murine RNA tumor virus replication and oncogenesis by chloroquine

“…The origin of the virus stocks has been described previously (Tennant et al, 1973). Moloney murine sarcoma virus (MSV) stocks contain a helper component, Moloney murine leukemia virus (MLV), and so are referred to as MSV(MLV).…”

“…S M E cells grown on coverslips and infected with MLV in the presence of different concentrations of chloroquine were washed and fixed with cold acetone at various times after infection and stored at -20" C. The coverslips were stained by methods described previously (Tennant and Richter, 1972;Tennant et al, 1973), and counts were made of the total cell numbers and the numbers of cells that were positive for fluorescence.…”

Effect of Chemically Modified 70 S RNA from Avian Myeloblastosis Virus (AMV) upon the Activity of AMV DNA Polymerase

“…Polymers studies included polyadenylic acid, poly (2'-o-methyl adenylic acid) (16) and polyuridylic acid (5,16,17). Interest in these inhibitors has been amplified by reports that certain polymers inhibit viral replication (15,16). Synthetic polymers have also been exploited as probes to study the mechanism of catalysis by DNA polymerases.…”