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Biomedical subjects

R M Friedman

Publications and source records attributed to R M Friedman.

At least 127 records · Page 7Linked to original sources
PubMed1983

Low infectivity of vesicular stomatitis virus (VSV) particles released from interferon-treated cells is related to glycoprotein deficiency.

We have investigated the mechanism for the low infectivity of vesicular stomatitis virus (VSV) released from interferon (IFN) -treated cells. With 10-30 units/ml of IFN there was an approximately 5-30 fold reduction in the production of virus particles, as measured by VSV proteins; however, the infectivity of the VSV released from IFN-treated mouse LB, JLS-V9R, or human GM2504 was drastically reduced (2 to 4 logs). The low infectivity of VSV was directly related to a deficiency in virion glycoprotein (G). IFN treatment did not change the specific infectivity of the VSV particles released by HeLa cells; their G protein was also not reduced. A further effect of IFN to reduce the amount of virion M protein appeared to be secondary and was probably not related to the reduced infectivity of VSV.

Animals↗
PubMed1983

Interferon-induced 2'-5' adenylate synthetase in vivo and interferon production in vitro by lymphocytes from systemic lupus erythematosus patients with and without circulating interferon.

The interferon (IFN)-induced enzyme 2-5A synthetase was elevated in mononuclear cells from both serum IFN-positive and -negative systemic lupus erythematosus (SLE) patients. This suggests that a much higher percentage of patients than previously thought produce endogenous IFN. These results may partly explain findings that mononuclear cells from SLE patients are deficient in IFN production in vitro in response to certain IFN inducers. Although normal lymphocytes can produce an acid-labile alpha IFN after stimulation with C. parvum in vitro, the reason for endogenous production of this unusual alpha IFN by SLE patients remains unknown.

2',5'-Oligoadenylate Synthetase↗
PubMed1983

Tunicamycin enhances the antiviral and anticellular activity of interferon.

The inhibitory effects of interferon on virus multiplication and cell growth are significantly enhanced by treatment with tunicamycin. Potentiation of antiviral activity was found only with enveloped viruses and not with nonbudding viruses. Changes in the plasma membrane of treated cells may account for this effect, since enveloped viruses bud from the cell surface as a terminal step.

Animals↗
PubMed1983

Interferon-induced synthesis of 2-5A-dependent RNase in mouse JLS-V9R cells.

Interferon treatment of mouse JLS-V9R cells resulted in a 10- to 20-fold increase in the levels of the 2-5A (ppp(A2'p)nA)-dependent RNase. The nuclease was monitored in cell extracts by covalent and noncovalent binding of 32P-labeled 2-5A derivatives to the nuclease and by the appearance of 2-5A-mediated ribosomal RNA cleavage products. Untreated JLS-V9R cells contained very low levels of the nuclease (5-10% of that found in control Ehrlich ascites tumor cells). An increase in the nuclease was first detected between 3 and 6 hr after interferon treatment and was completely inhibited by actinomycin D. Control experiments indicated that the increase in the nuclease was not due to an intracellular redistribution of the enzyme. The results indicate that in JLS-V9R cells, interferon controls the activity of the 2-5A system at two levels: by inducing the synthesis of both the 2-5A-dependent RNase and the 2-5A-synthetase.

2',5'-Oligoadenylate Synthetase↗
PubMed1983

Induction of ppp(A2'p)nA-dependent RNase in murine JLS-V9R cells during growth inhibition.

We recently reported that interferon induces the synthesis of ppp(A2'p)nA(n = 2 to greater than or equal to 4) (2-5A)-dependent RNase in the murine cell line JLS-V9R. These cells normally contain very low levels of the nuclease; after interferon treatment, however, they develop levels approaching those found in murine L or Ehrlich ascites tumor cells. Here, we report a similar increase in the nuclease levels in JLS-V9R cells during the transition from the subconfluent actively growing state to the confluent stationary phase. Levels of 2-5A synthetase increased in parallel with the nuclease. The induced levels of both the nuclease and synthetase returned to low basal amounts after trypsinization, dilution, and culturing of the cells at subconfluent densities. The addition of anti-murine interferon (alpha + beta) antibodies to the medium did not affect the induction of the nuclease nor could any interferon be detected in the culture supernatants as determined by the lack of antiviral activity. The increase in the enzymes was not, therefore, due to the spontaneous production of interferon. The induction of the nuclease during confluency preceded an inhibition of [3H]-thymidine incorporation by the cells into DNA. The regulation of the 2-5A-dependent RNase in JLS-V9R cells may, therefore, be related to the control of cell growth.

2',5'-Oligoadenylate Synthetase↗
PubMed1983

Interferon induces the production of membrane protein-deficient and infectivity-defective vesicular stomatitis virions through interference in the virion assembly process.

The reduced rate of synthesis, maturation and degradation as well as the level of accumulation of the intracellular virus proteins in VSV-infected cells may account for the overall reduction (less than 10-fold) of progeny virion yield due to interferon (IFN); however, the deficiency of the virions proteins, G and M, which apparently caused a drastic loss of infectivity of these progeny virions (about 1000-fold) cannot be easily explained, because the concentrations of G and M proteins relative to other virus proteins were not reduced in the cell. In fact, intracellular M protein was significantly increased. Moreover, the virus proteins in IFN-treated and control cells were synthesized and accumulated in large excess of the amount incorporated into the released virions. The reduction in the intracellular activity of GlcNac-P-P-Dol transferase did not appear to play a direct role in the antiviral mechanism in this system. Our results, however, do suggest that the deficiency of G and M proteins in the virion is related to specific inhibition of the incorporation of either or both of these proteins in the virus assembly process.

Interferons↗
PubMed1983

Tunicamycin treatment inhibits the antiviral activity of interferon in mice.

Earlier we reported that tunicamycin (TM) treatment of L cells in vitro significantly enhances the antiviral activity of interferon (IFN) against viruses (such as vesicular stomatitis, Sindbis, and herpes simplex) which bud from membranes. However, no such enhancement of the antiviral activity of IFN by TM was observed against encephalomyocarditis virus (EMCV) (nonbudding). We were interested to know whether TM would similarly enhance the antiviral activity of IFN and IFN inducers in vivo against Semliki Forest virus (SFV) and EMCV infections in mice. It was observed that TM alone (0.001 to 5.0 micrograms per mouse) did not protect mice against infections of SFV and EMCV; instead, TM-treated mice died with virus-specific paralytic symptoms earlier than untreated animals. The enhanced mortality in TM-treated and SFV- or EMCV-infected mice was associated with the concomitant increase in virus titer in brain tissue. IFN significantly protected mice against SFV and EMCV infections. The antiviral protection of mice by IFN against both the viruses was markedly inhibited by TM administration. IFN inducers (polyinosinic acid-polycytidylic acid, 6-MFA [a mixture of proteins, polysaccharides, and double-stranded DNA isolated from Aspergillus ochraceus ATCC 28706]) protected a significant number of mice against SFV infection. However, no such protection was observed in mice injected with a combination of TM and IFN inducer. These results indicate that TM treatment inhibits the antiviral action of IFN or IFN inducers in vivo.

Animals↗
PubMed1983

Reexamination of the morphogenetic block of a putative late-stage, temperature-sensitive mutant of Moloney murine leukemia virus.

The ts3 temperature-sensitive mutant of Moloney murine leukemia virus has been reported to have a morphogenetic block in a late stage of the budding process. As evidence, previously published electron micrographs of cells maintained at the nonpermissive temperature (39 degrees C) revealed numerous budding virions on the cell surface. However, it appears now that these micrographs reflected budding that occurred not at 39 degrees C, but after cells were removed from the incubator before fixation. The morphogenesis of ts3 is actually blocked at an earlier stage of development.

Microbiological Techniques↗
PubMed1983

Interferon-induced alterations in cells: relevance to viral and nonviral diseases.

Thus, interferon has diverse effects on cellular structure and/or function. Although some of these effects may be involved in interferon's antiviral actions, they may also play a role in normal physiologic processes. Inappropriate production of or response to interferon may, therefore, contribute to abnormal cell-cell interactions seen in a variety of disease states. In view of the increasingly widespread use of human interferons in antiviral and anticancer therapy, further investigation is needed to understand the many effects of interferons on cells. For example, insight into the biologic properties of each of the numerous subspecies of alpha-interferon may allow more rational decisions about the type of interferon, dose, and administration schedule necessary for maximal beneficial effects in cancer patients. Further studies on the immunoregulatory effects of the different types of interferons are also necessary to elucidate whether interferon is involved in the pathophysiology of immune disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Systemic lupus erythematosus: presence in human serum of an unusual acid-labile leukocyte interferon.

A previously undescribed species of human leukocyte, or alpha, interferon is present in the serum of many patients with systemic lupus erythematosus. It was shown to be alpha-interferon by neutralization with specific antiserums, affinity column chromatography, and antiviral activity on bovine cells. However, 23 of 30 interferon samples tested were inactivated by incubation at pH 2, a characteristic of human "immune," or gamma, interferon. Multiple samples of interferon from the same patient had similar biological properties, but samples from different patients were not all identical, suggesting that several variants of this species of human alpha-interferon may exist.

Humans↗
PubMed1982

Interferon redux.

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Interferons↗
PubMed1982

Interferon induces morphologic reversion with elimination of extrachromosomal viral genomes in bovine papillomavirus-transformed mouse cells.

The effect of mouse L-cell interferon on bovine papillomavirus type 1 (BPV-1) transformation of murine cells was examined. Mouse interferon reduced the level of BPV-1-induced transformation of mouse C127 cells by 95%. Long-term treatment of established BPV-1-transformed mouse cell clones with mouse L-cell interferon led to a decrease in the average number of the plasmid viral genomes present in these cells to 1/3 to 1/8. Although revertant lines could not be isolated from these lines in the absence of treatment with interferon, flat revertants were easily selected from two independent clonal transformed lines carried for 60 generations in the continued presence of 200 units of interferon per ml. These flat revertants had the biological characteristics of nontransformed C127 cells and could be retransformed by BPV-1. Southern blot hybridization failed to detect BPV-1 DNA in any of eight independent revertant lines examined under conditions that could detect 0.2 copies per cell. We conclude that interferon treatment has resulted in a selective reduction of the amount of extrachromosomal BPV-1 DNA in transformed cells and has cured some treated cells completely of their viral DNA.

Bovine papillomavirus 1↗
PubMed1982

Interferon interactions with thyroid cells.

Iodide uptake by functioning rat thyroid (FRTL) cells is increased by mouse interferon. The effect is detectable using purified interferon; it is not accompanied by an increase in intracellular cyclic AMP levels, is measurable within 20 min, and is prevented by cholera toxin, an agent which inhibits interferon's antiviral activity. The effect of interferon is biphasic with maximally increased iodide uptake (approximately 2-fold) evident at about 300 international mouse units per ml (U/ml) and lesser effects evident at higher concentrations (greater than 1000 U/ml). The effect of mouse interferon on iodide uptake is accompanied by an extremely sensitive antiviral response. Thus, significant antiviral protection is evident at 1 U/ml with FRTL cells, as opposed to 1000 U/ml for nonfunctioning rat thyroid (FRT) cells. Functioning FRTL thyroid cells are also more sensitive to mouse interferon (10-fold) with respect to 2',5'-polyadenylate (An) synthetase activity or to 125I-thyrotropin binding to membrane preparations than are nonfunctioning FRT cells. Antiviral protection in FRTL cells is evident as early as 1 h after exposure to mouse interferon, and is accompanied by a nearly 100-fold increase in the measurable titer of 2'5'-An synthetase activity. Actinomycin D blocks the antiviral effect of interferon, but not its effect on iodide uptake. The results are discussed with respect to the unusually sensitive response of heterologous (rat) cells to mouse interferon: a possible relationship between thyrotropin and interferon receptors; and, the difference in interferon sensitivity exhibited by differentiated (functioning) as opposed to undifferentiated (nonfunctioning) thyroid cells.

2',5'-Oligoadenylate Synthetase↗
PubMed1982

Interferon-mediated inhibition of adenylate cyclase in mouse cells.

Adenylate cyclase activity was measured in mouse cell plasma membrane after 30 units/ml of interferon (IFN) treatment. The basal and Gpp(NH)p stimulated enzyme activity in LB cell was inhibited by 20%-40% throughout the time course of treatment (30 min to 18 h). The reduced enzyme activity was not associated with enhanced breakdown of cAMP, but was related to alteration in the catalytic component of the enzyme. Moreover, there was no change in the affinity for guanine-nucleotide regulatory unit and 1 X 10(-7) M Gpp(NH)p was required to obtain half-maximal activation with either type of membrane. Interferon action on adenylate cyclase was biphasic, at 10 u/ml it was stimulatory and between 30 and 1000 u/ml it inhibited the enzyme activity to a great extent; but IFN did not exert its effect directly on the enzyme. The reduction in enzyme activity was comparable to a reduction in the intracellular level of cAMP in most of the interferon-sensitive cell lines studied. We propose, therefore, that the inhibitory effect on adenylate cyclase is related to a step in the development of antiviral activity.

1-Methyl-3-isobutylxanthine↗