Inhibition of glycosylation processing alters the growth parameters of cells transformed by the oncogene of simian sarcoma virus.

Normal rat kidney (NRK) cells transformed by the v-sis oncogene of simian sarcoma virus (SSV) were treated with the glucosidase I inhibitor castanospermine. The inhibitor did not change cell morphology, but specific growth parameters such as serum- and anchorage-independence were lost.

The effect of hexadimethrine bromide (polybrene) on the infection of the primate retroviruses SSV 1/SSAV 1 and BaEV.

Polybrene was shown to enhance the adsorption of simian sarcoma virus-simian sarcoma associated virus complex (SSV-1/SSAV-1) and baboon endogenous virus (BaEV) onto cells in culture. A 16- to 18-fold increased adsorption of both viruses occurred at 8 micrograms/ml polybrene within one hour after infection. The polybrene mediated adsorption was found to be inhibited by the addition of tri-sodium citrate to the culture medium, suggesting the involvement of electrostatic forces. This contention was further supported by the demonstration of temperature independence of the polybrene mediated interaction.

Diverse effects: augmentation, inhibition, and non-efficacy of 12-O-tetradecanoylphorbol-13-acetate (TPA) on retrovirus genome expression in vivo and in vitro.

The action of 12-O-tetradecanoylphorbol-13-acetate (TPA) on several retrovirus-related functions was investigated in four virus-host cell systems. The following effects were recorded: (i) in STU-mice, infected with the Friend virus complex (Friend) murine leukaemia virus/Friend spleen focus forming virus) and treated with TPA (50 ng/g) for one week prior to infection, the number of spleen foci increased 5-fold over the control. (ii) Addition of TPA (0.04 to 40 ng/ml) to virus-producing cell systems resulted in a 2-fold increase of extracellular reverse transcriptase activity. The maximum response was observed in Friend leukemia virus-producing mouse cells at 0.1 to 0.4 ng TPA/ml and in simian sarcoma virus-producing rat cells at 4 ng/ml. (iii) The efficiency of transformation of BalbC 3T3 cells by Moloney murine sarcoma virus, tested in a focus formation assay, was slightly enhanced by TPA. (iv) TPA inhibited the induction of endogenous virus formation in B cell mitogen-stimulated spleen cell cultures from BalbC mice.

Antiviral properties of polyinosinic acids containing thio and methyl substitutions.

Polyinosinic acids containing methyl and sulphur substitutions are potent inhibitors of reverse transcriptase. Substitution of sulphur for oxygen at the 6 position produces significant effects on the properties of polyinosinic acid: the kinetics of inhibition change from competitive to mixed-type and the inhibition constant falls by three orders of magnitude. In contrast, 1-methyl substitution produces no such effects. Poly(1-methyl-6-thioinosinic acid) or poly(m1s6I) inhibits irreversibly, inhibiting all ten reverse transcriptases tested under a variety of assay conditions. In cell culture test systems, poly(m1s6I) is capable of blocking both infection by non-transforming viruses and transformation by a sarcoma virus. The presence of poly(m1s6I) in a preinfected culture results in the production of non-infectious virus particles lacking reverse transcriptase activity.

Quantitative structure--activity correlations of rifamycins as inhibitors of viral RNA-directed DNA polymerase and mammalian alpha and beta DNA polymerases.

Twenty-two 3-substituted rifamycins were tested for inhibition of mammalian alpha and beta DNA polymerase and viral RNA-dependent DNA polymerase ("reverse transcriptase"). Quantitative structure--activity relationships (QSAR) were formulated for the three systems. Inhibition is linearly dependent on the partition coefficient and is highly favored by the presence of bulky hydrazones or oximes. None of these agents proved to be a selective or specific inhibitor of reverse transcriptase. A correlation in terms of log P and (log P)2 was obtained from data on a more closely related set of analogues from a published study. For murine reverse transcriptase, log P0 = 5.1.

Interruption of oncornavirus replication by modified rifamycin antibiotics.

Thirteen rifamycin SV derivatives containing 3'-alkylaminomethyl substituents fail to inhibit the activities of the simian sarcoma virus Type 1 DNA polymerase, and of cellular DNA, RNA, and poly(A) polymerases prepared from NIH Swiss mouse embryos. These compounds show a range in their toxicities for NIH Swiss mouse 3T3 cells and in their capacities to inhibit production of foci of morphologically altered cells by murine sarcoma virus (MSV). Three compounds--the N-methyl-N-hydroxyethylaminomethyl, the N,N-dimethyl-aminomethyl, and the N4-methylpiperazinomethyl rifamycin derivatives--are comparable to adenine arabinoside and ribavirin in their toxicity for 3T3 cells, but these compounds show superior focus inhibition. These compounds inhibit oncornavirus production apparently by exacerbation of a delay in growth that results from infection of 3T3 cells with MSV.