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PubMed1976

The binding of poly(rA) and poly(rU) to denatured DNA. I. Model studies with homopolymers.

We have compared the properties of the poly(rA).oligo(dT) complex with those of the poly(rU).oligo(dA)n complex. Three main differences were found. First, poly(rA) and oligo(dT)n do not form a complex in concentrations of CsCl exceeding 2 M because the poly(rA) is insoluble in high salt. If the complex is made in low salt, it is destabilized if the CsCl concentration is raised. Complexes between poly(rU) and oligo(dA)n, on the other hand, can be formed in CsCl concentrations up to 6.6 M. Second, complexes between poly(rA) and oligo(dT)n are more rapidly destabilized with decreasing chain length than complexes between poly(rU) and oligo(dA)n. Third, the density of the complex between poly(rA) and poly(dT) in CsCl is slightly lower than that of poly(dT), whereas the density of the complex between poly(rU) and poly(dA) in CsCl is at least 300 g/cm3 higher than that of poly(dA). These results explain why denatured natural DNAs that bind poly(rU) in a CsCl gradient usually do not bind poly(rA).

Binding Sites↗
PubMed2002

Poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly (D,L-lactic acid-co-glycolic acid) triblock copolymer and thermoreversible phase transition in water.

Novel thermoreversible gelation behavior of aqueous solutions of ABA-type triblock copolymers composed of the central polyethylene oxide (PEG) block and two poly(D,L-lactic acid-co-glycolic acid) side blocks was found. Phase transition characteristics, such as critical gel concentration (CGC) and lower and upper critical gel temperature (CGT), are closely related to the molecular structure of the triblock copolymers. The CGC and the lower CGT both increases with increasing PEG/PLGA molecular weight ratio. Increasing the GA content in PLGA block induces a somewhat higher CGC. The copolymer forms micelles with a PLGA loop core and a PEG shell in water. Also grouped micelles are identified seemingly due to the bridging of two micelles sharing two PLGA blocks of a block copolymer chain. As the temperature increases the association of micelles increases, which results in gelation. The ABA-type copolymers exhibit a relatively low CGC (<10%) and low sol-gel transition temperatures compared to BAB-type copolymers. As the temperature increases further gel-sol transition is observed, which would result from the shrinkage of micelles with temperature increase. The hydrodynamic size of the micelles is monitored by dynamic laser scattering, and a possible gelation mechanism was suggested.

Gels↗
PubMed2006

Release characteristics of diclofenac sodium from poly(vinyl alcohol)/sodium alginate and poly(vinyl alcohol)-grafted-poly(acrylamide)/sodium alginate blend beads.

In this study, acrylamide (AAm) was grafted onto poly(vinyl alcohol) (PVA) with UV radiation at ambient temperature. The graft copolymer (PVA-g-PAAm) was characterized by using Fourier transform infrared spectroscopy (FTIR), elemental analysis and differential scanning calorimetry (DSC). Polymeric blend beads of PVA-g-PAAm and PVA with sodium alginate (NaAlg) were prepared by cross-linking with glutaraldehyde (GA) and used to deliver a model anti-inflammatory drug, diclofenac sodium (DS). Preparation condition of the beads was optimized by considering the percentage entrapment efficiency, particle size, swelling capacity of beads and their release data. Effects of variables such as PVA/NaAlg ratio, acrylamide content, exposure time to GA and drug/polymer ratio on the release of DS were discussed at three different pH values (1.2, 6.8, 7.4). It was observed that, DS release from the beads decreased with increasing PVA/NaAlg (m/m) ratio, drug/polymer ratio (d/p) and extent of cross-linking. However, DS release increased with increasing acrylamide content of the PVA-g-PAAm polymer. The highest DS release was obtained to be 92% for 1/1 PVA-g-PAAm/NaAlg ratio beads. It was also observed from release results that DS release from the beads through the external medium is much higher at high pH (6.8 and 7.4) than that at low pH (1.2). The drug release from the beads mostly followed Case II transport.

Acrylamides↗
PubMed1999

Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic)/poly(epsilon-caprolactone) (PCL) amphiphilic block copolymeric nanospheres. I. Preparation and characterization.

Amphiphilic block copolymers based on PEO-PPO-PEO block copolymer (Pluronic) and poly(epsilon-caprolactone) were synthesized by bulk polymerization. The structural analysis of Pluronic/PCL block copolymer was carried out using FT-IR, 1H NMR, GPC, WAXD, DSC and TGA measurements. To prepare copolymeric nanospheres with a micellar structure, Pluronic/PCL amphiphilic block copolymers were dialyzed against water. The size and size distribution of Pluronic/PCL block copolymeric nanospheres were examined by dynamic light scattering measurement. They showed an average diameter of 116 to 196 nm depending on the type of copolymer. All the nanosphere samples exhibited a narrow size distribution. The critical micelle concentrations of Pluronic/PCL amphiphilic block copolymers determined by fluorescence spectroscopy were lower than that of common low molecular weight surfactants. We confirmed the formation of stable copolymeric nanospheres through the solution behavior of amphiphilic block copolymer in selective solvents.

Drug Delivery Systems↗
PubMed2000

Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)/poly(epsilon-caprolactone) (PCL) amphiphilic block copolymeric nanospheres. II. Thermo-responsive drug release behaviors.

Amphiphilic block copolymers composed of relatively hydrophilic PEO-PPO-PEO block copolymer (Pluronic) and poly (epsilon-caprolactone) with hydrophobic character were synthesized by ring-opening polymerization of epsilon-caprolactone in the presence of PEO-PPO-PEO block copolymer using stannous octoate as a catalyst. Pluronic/PCL block copolymeric nanospheres with core-shell structure were prepared by dialysis method. They showed the average diameter of 116-196 nm depending on the type of copolymer. All the nanosphere samples exhibited a narrow size distribution. The critical micelle concentrations of Pluronic/PCL amphiphilic block copolymers determined by fluorescence spectroscopy were lower than that of the common low molecular weight surfactant. Their core-shell structure was confirmed by 1H NMR spectroscopy. Pluronic/PCL block copolymeric nanospheres exhibited the reversible change of size depending on the temperature. Release behaviors of indomethacin from Pluronic/PCL block copolymeric nanospheres also showed temperature dependence and a sustained release pattern. In addition, cytotoxicity test using an MTT assay method revealed that these indomethacin-loaded Pluronic/PCL nanospheres could remarkably reduce the cell damage compared with the unloaded free indomethacin.

Algorithms↗
PubMed2001

Surface morphology of poly(caprolactone)-b-poly(dimethylsiloxane)-b-poly(caprolactone) copolymers: effects on protein adsorption.

Certain triblock copolymer surfaces have beneficial blood contacting properties that remain unexplained from a mechanistic perspective. In this study, poly(caprolactone-block-dimethylsiloxane-block-caprolactone) (PCL-b-PDMS-b-PCL) surfaces are characterized by dynamic contact angle analysis, angle-resolved X-ray photoelectron spectroscopy (XPS), and phase detection imaging atomic force microscopy (AFM). Surface morphology of films cast from 10 wt % MEK solutions are found to be semicrystalline possessing spherulites on the micron scale and alternating semicrystalline PCL-rich and amorphous PDMS-rich lamellae on the nanometer scale. Surface enrichment of the lower surface free energy block, PDMS, is observed using angle-resolved XPS but the surface composition still consists of both copolymer blocks. Films cast from 1 wt % solutions showed similar morphologies but incomplete surface coverage. Different textural features of adsorbed fibrinogen layers on coated and uncoated polypropylene are observed. The hypothesis that patterned block copolymer surfaces can affect protein adsorption and thus influence compatibility is partially supported by the findings of this study.

Adsorption↗
PubMedDate not supplied

Enhanced bone marrow stromal cell adhesion and growth on segmented poly(ether ester)s based on poly(ethylene oxide) and poly(butylene terephthalate).

In previous studies in rats and goats, hydrophilic compositions of the PEOT/PBT block copolymer family have shown in vivo calcification and bone bonding. These copolymers are therefore interesting candidates as scaffolding materials in bone tissue engineering applications. Model studies using goat bone marrow stromal cells, however, showed that it was not possible to culture bone marrow stromal cells in vitro on these hydrophilic copolymers. In this paper two ways of surface modifying these materials to improve in vitro bone marrow stromal cell attachment and growth are discussed. Two different approaches are described: (1) blending of hydroxyapatite (HA) followed by CO(2) gas plasma etching; (2) surface modification using CO(2) gas plasma treatments. It was observed that not only HA but also the CO(2) plasma treatment by itself has a positive effect on bone marrow stromal cell attachment and growth. Gas plasma treatment appeared to be the most successful approach, resulting in a large increase in the amount of bone marrow stromal cells present on the surface (determined by a DNA assay). The amount of DNA present on the plasma-treated copolymer 1000/70/30 PEOT/PBT, based on poly(ethylene oxide, M(w) = 1000, 70 m% soft segment), was comparable to the amount present on PDLLA and significantly higher than the amount present on PCL after 7 days of cell culturing. The fact that after gas plasma treatment bone marrow stromal cells do attach to PEOT/PBT copolymers, enables in vitro bone marrow stromal cell culturing, making bone tissue engineering applications of these materials possible.

Animals↗
PubMed2001

Effects of ethylene oxide gas sterilization on physical properties of poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) microspheres.

The aggregation of poly(alpha-hydroxy acid) microspheres during ethylene oxide (EO) gas sterilization makes it difficult for the microspheres to be used in clinical applications. In this study, six kinds of PLLA-PEG-PLLA triblock copolymers (TriPLE) were synthesized with various composition ratios of PEG/PLLA in the range of 0.012 to 0.103. TriPLE microspheres were prepared by the oil-in-water emulsion method. TriPLE microspheres were characterized by using 1H-NMR, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). After sterilization by EO gas at 55 degrees C, the microspheres were analyzed by scanning electron microscope (SEM), laser diffractometry, standard sieves, X-ray diffraction (XRD), GPC, and DSC. When the composition ratio of PEG/PLLA was above 0.02, the initial crystallinity of TriPLE in microspheres was as high as 50%, and the microspheres were suitable to be sterilized by EO gas. On the other hand, TriPLE microspheres, which had composition ratios of PEG/PLLA below 0.02, had low initial crystallinities of about 30%, and aggregated during EO gas sterilization. For these microspheres, crystallinity increased up to 50% during the sterilization, whereas other TriPLE microspheres did not show any changes in crystallinity. Therefore, the aggregation of TriPLE microspheres during EO gas sterilization was markedly reduced as the initial crystallinity of TriPLE in the microspheres was increased.

Calorimetry, Differential Scanning↗
PubMed1974

Interferon induction by poly (I): poly (C) enclosed in phospholipid particles.

Liposomes were prepared with phospholipids (sphingomyelin, lecithin, and phosphatidylethanolamine) in combination with cholesterol and charged lipids (dicetyl phosphate and stearylamine) and contained either poly(I):poly(C) or poly(I). Neutral and positively charged liposomes attached much better to L-929 cells in tissue culture than did negatively charged particles. Liposomes were toxic to L cells at relatively low concentrations, making the determination of antiviral activity induced by particles containing poly(I):poly(C) difficult to measure by the plaque reduction assay. When injected into mice, all of the liposomes containing poly(I):poly(C), except phosphatidylethanolamine liposomes, greatly potentiated and extended the serum interferon response of poly(I):poly(C). Lecithin and sphingomyelin liposomes given intravenously were ten times more effective than free poly(I):poly(C) in stimulating production of serum interferon. Sphingomyelin liposomes containing [(14)C]poly(I):poly(C) were 88% cleared from the bloodstream of mice by 3 min after intravenous injection. Most of the radioactivity (70%) was captured by the liver and remained there for at least 4 h. By 2 h, 7% of the radioactivity could be found in the spleen. Five percent of the radioactivity was found in the lungs at 30 min, with decreasing amounts thereafter. Small amounts of radioactivity were found in the muscle and kidneys. The spleen was shown to contain appreciable levels of interferon at 4 h, and low levels were found in the liver. Radioactivity accumulated slowly in the liver following an intraperitoneal injection of sphingomyelin liposomes containing [(14)C]poly(I):poly(C). By 4 h, 26% of the dose was recovered from the liver and 4.9% from the spleen, with small amounts in the lung, kidney, and omentum.

Animals↗
PubMed1982

Poly(dT) inhibition of globin synthesis in the rabbit reticulocyte lysate system. Reversal of the inhibition by poly(dT)-binding protein.

The mechanism of inhibition of globin synthesis by poly(dT) was studied in the rabbit reticulocyte lysate system. When the lysate was incubated with [14C]poly(dT), poly(dT) was found to bind with the native 40S ribosomal subunit and the "supernatant factor." But the binding to the native 40S ribosomal subunits was not directly related to the poly(dT) inhibition. Ribosomal subunits were prepared from rabbit reticulocytes and tested for their binding with poly(dT) and their effect on the poly(dT) inhibition. Poly(dT) was found to bind with the derived 40S ribosomal subunit, but not with the derived 60S subunit, and the poly(dT) inhibition was slightly reversed by the derived 40S ribosomal subunit. Under conditions such that the elongation of nascent chains was inhibited by sparsomycin, the formation of the 80S/Met-tRNAf complex was inhibited by poly(dT) and the inhibition was greater at high concentration of KOAc. However, the formation of the 40S/Met-tRNAf complex was inhibited to the same extent at 70 mM and 200 mM KOAc in the presence of GMPPCP. A factor (TF) that reverses the poly(dT) inhibition was partially purified from the KCl-wash of rabbit reticulocyte ribosomes by ammonium sulfate fractionation, and Sephadex G-150 and DEAE-cellulose column chromatographies. From the Sephadex G-150 and DEAE-cellulose column chromatography of TF, the molecular weight of TF was estimated to be 81,000-102,000. TF reversed the poly(dT) inhibition of 80S/[3H]mRNA/Met-tRNAf complex or that of 40S/[3H]mRNA/Met-tRNAf complex. TF bound to [14C]poly(dT) or 3H-labeled globin mRNA. SDS/polyacrylamide slab gel electrophoresis of the complexes between the factor and [14C]poly(dT) or [3H]mRNA showed common polypeptide bands of 22,500, 25,000, and 49,000 daltons. These data can be explained by assuming that poly(dT) binds to a factor which is required for the binding of 40S/Met-tRNAf complex with mRNA to form inactive complexes, and thus inhibits globin synthesis. The relationship between the poly(dT)-binding protein and known initiation factors is discussed.

Animals↗
PubMed1995

Comparison of base inclination of ribo-GC and deoxyribo-GC polymers, and synthesis of poly(rGrC)-poly(rGrC).

The inclination angle between the base normal and the helix axis, and the axes around which the bases incline, are measured for ribo-GC polymers in buffer by using flow linear dichroism (LD), and compared to measurements for deoxyribo-GC polymers in buffer and under dehydrating conditions. A new method is designed to synthesize poly(rGrC)-poly(rGrC), which is not available commercially, in large quantities. The LD of this RNA reveals inclination angles that are similar to the B-form DNA in buffer, although the axes are different. The CD of poly(dGdC)-poly(dGdC) under the dehydrating conditions is similar to poly(rGrC)-poly(rGrC), indicating it is in the A form, and the LD gives larger inclination angles than either the B form or the corresponding RNA. Poly(dG)-poly(dC) is in the A form in buffer. Comparison among poly(rG)-poly(rC) in buffer, and poly(dG)-poly(dC) in buffer under dehydrating conditions, reveals similar inclination angles and axes, although the LD shows that the DNA has the largest inclination angles. Except for poly(rGrC)-poly(rGrC), which has a unique reduced dichroism, all the axes for G are similar, as are the axes for C.

Circular Dichroism↗
PubMed1980

Demonstrations of the production of specific antibodies to poly(I).poly(C) in rabbits.

The rabbit antiserum against poly(I).poly(C) purified by hydroxyapatite column chromatography contained three distinct antibodies. They were fractionated into three antibody populations by a series of precipitations (with poly(A).poly(U), poly(I), and poly(I).poly(C)) and their specificities were examined by quantitative complement fixation, double diffusion tests and radioimmunoassay. The first population was common to the double helical structure of double-stranded RNAs. The second was specific for poly(I) and the third was specific for poly(I).poly(C). These studies demonstrated that specific antibodies exclusively reactive with poly(I).poly(C) existed in the rabbit antiserum against poly(I).poly(C).

Animals↗
PubMed1989

The roles of protein kinase C and cyclic nucleotide dependent kinase in signal transduction in human interferon gamma induction by poly I:poly C.

The signal transduction mechanisms involved in interferon (IFN) gamma induction in human peripheral mononuclear lymphocyte nylon-nonadherent cells (NNA cells) by stimulation with poly(I):poly(C) are investigated. Significant enhancement of IFN gamma production by poly(I):poly(C) is observed in the presence of the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA, a protein kinase C (PKC) activator). Our study shows that in NNA cells, poly(I):poly(C) with or without TPA causes prolonged activation of cytosolic PKC of NNA cells for at least 120 min. The level of activation of PKC is quite remarkable in the case of the combined stimulation by poly(I):poly(C) and TPA as compared to poly(I):poly(C) alone. This demonstrates that prolonged activation of cytosolic PKC for at least 120 min is essential for high levels of production of IFN gamma. Moreover, inhibition experiments using the PKC inhibitor H-7 and cAMP-dependent protein kinase inhibitor H-8 suggest that the mechanism of signal transduction with regard to PKC is involved in stimulation of IFN gamma production in NNA cells by poly(I):poly(C) in the presence of TPA and that along with PKC, cAMP-dependent protein kinase is probably involved in induction of IFN gamma by stimulation with poly(I):poly(C) alone.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1986

1H two-dimensional nuclear Overhauser effect and relaxation studies of poly(dA).poly(dT)

The structure of poly(dA).poly(dT) in aqueous solution has been studied by using 1H two-dimensional nuclear Overhauser effect (2D NOE) spectroscopy and relaxation rate measurements on the imino and nonexchangeable protons. The assignments of the 1H resonances are determined from the observed cross-relaxation patterns in the 2D NOE experiments. The cross-peak intensities together with the measured relaxation rates show that the purine and pyrimidine strands in poly(dA).poly(dT) are equivalent in aqueous solution. The results are consistent with a right-handed B-form helix where the sugars on both strands are in the C2'-endo/anti configuration. These observations are inconsistent with a proposed heteronomous structure for poly(dA).poly(dT) [Arnott, S., Chandrasekaran, R., Hall, I. H., & Puigjaner, L. C. (1983) Nucleic Acids Res. 11, 4141-4155]. The measured relaxation rates also show that poly(dA).poly(dT) has fast, large-amplitude local internal motions (+/- 20-25 degrees) in solution and that the amplitudes of the base and sugar motions are similar. The motion of the bases in poly(dA).poly(dT) is also similar to that previously reported for poly(dA-dT).poly(dA-dT) and poly(dG-dC).poly(dG-dC) [Assa-Munt, N., Granot, J., Behling, R. W., & Kearns, D. R. (1984) Biochemistry 23, 944-955; Mirau, P. A., Behling, R. W., & Kearns, D. R. (1985) Biochemistry 24, 6200-6211].

Kinetics↗
PubMed1987

Infrared and Raman studies show that poly(dA).poly(dT) and d(AAAAATTTTT)2 exhibit a heteronomous conformation in films at 75% relative humidity and a B-type conformation at high humidities and in solution.

The decadeoxynucleotide d(AAAAATTTTT)2 in duplex form and the double-helical polynucleotide poly(dA).poly(dT) have been studied by Raman and infrared (IR) spectroscopy under a variety of environmental conditions. The IR spectra have been taken of cast films and compared to the IR spectra of the alternating poly(dA-dT), which shows clear B-genus and A-genus vibrational spectra under conditions of high (greater than 92%) and low (75%) relative humidity (RH). From the IR data, it is shown that d-(AAAAATTTTT)2 and poly(dA).poly(dT) adopt a B-genus conformation in films with high water content. When the relative humidity of the film is decreased, the IR spectra reflect a gradual evolution of the geometry of both d(AAAAATTTTT)2 and poly(dA).poly(dT) into a form intermediate between the B genus and A genus, but the IR spectrum of a pure A genus has not been obtained. In these DNAs at 75% RH, the IR bands of adenosine have the same frequencies as those found in poly(dA-dT) at 75% RH where the local furanose conformation is C3' endo/anti, but the thymidine frequencies do not resemble those of poly(dA-dT) at 75% RH but rather those of poly(dA-dT) at high humidities. It is concluded that both poly(dA).poly(dT) and d(AAAAATTTTT)2 adopt a fully heteronomous duplex geometry in cast films at low humidity. For studies in aqueous solution the Raman effect was employed. As a model for the heteronomous conformation in solution, the duplex poly(rA).poly(dT) was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1987

fd gene 5 protein binds to double-stranded polydeoxyribonucleotides poly(dA.dT) and poly[d(A-T).d(A-T)].

Circular dichroism (CD) data indicated that fd gene 5 protein (G5P) formed complexes with double-stranded poly(dA.dT) and poly[d(A-T).d(A-T)]. CD spectra of both polymers at wavelengths above 255 nm were altered upon protein binding. These spectral changes differed from those caused by strand separation. In addition, the tyrosyl 228-nm CD band of G5P decreased more than 65% upon binding of the protein to these double-stranded polymers. This reduction was significantly greater than that observed for binding to single-stranded poly(dA), poly(dT), and poly[d(A-T)] but was similar to that observed for binding of the protein to double-stranded RNA [Gray, C.W., Page, G.A., & Gray, D.M. (1984) J. Mol. Biol. 175, 553-559]. The decrease in melting temperature caused by the protein was twice as great for poly[d(A-T).d(A-T)] as for poly(dA.dT) in 5 mM tris(hydroxymethyl)aminomethane hydrochloride (Tris-HCl), pH 7. Upon heat denaturation of the poly(dA.dT)-G5P complex, CD spectra showed that single-stranded poly(dA) and poly(dT) formed complexes with the protein. The binding of gene 5 protein lowered the melting temperature of poly(dA.dT) by 10 degrees C in 5 mM Tris-HCl, pH 7, but after reducing the binding to the double-stranded form of the polymer by the addition of 0.1 M Na+, the melting temperature was lowered by approximately 30 degrees C. Since increasing the salt concentration decreases the affinity of G5P for the poly(dA) and poly(dT) single strands and increases the stability of the double-stranded polymer, the ability of the gene 5 protein to destabilize poly(dA.dT) appeared to be significantly affected by its binding to the double-stranded form of the polymer.

Circular Dichroism↗
PubMed1975

Are cytotoxicity and interferon inducing activity of poly(I).poly(C) invariably linked in interferon-treated L cells.

Interferon-treated L cells exhibit a specific enhanced susceptibility to the cytotoxic and interferon inducing activities of double-stranded RNAs such as poly(1). poly(C). These activities remained closely linked through widely varying assay conditions, involving, for example, different time anddosage schedules of poly(1). poly (C),suggesting that there is at least one common step in the mechanisms leading to interferon formation and toxicity in interferon-primed cells exposed to poly(1).poly(C). However, some procedures such as addition of metabolic inhibitors (actinomycin D, cycloheximide) and repeated administration of poly(1).poly(C) suppressed the interferon inducing capacity of poly(1).poly(C) without a concomitant decrease of toxicity. Other procedures such as brief treatment of the cells with interferon or DEAE-dextran permitted full expression of the interferon inducing activity of poly(1).poly(C) without any sign of toxicity. The latter results suggest that the mechanisms underlying interferon production and toxicity of poly(1).poly(C) in interferon-treated L cells diverge from a certain point onward.

Animals↗
PubMed1976

Investigation of the anti-viral mechanism of poly I and poly C against encephalomyocarditis virus infection in the absence of interferon induction in mice.

Protection of mice against EMC virus infection by poly C and poly I has already been distinguished from interferon mediated protection in several ways. Transfer of serum from EMC virus infected and poly C or poly I treated mice to donor mice that were then infected shows that the anti-viral effect of the single-stranded polynucleotides is not due to boosting interferon produced by infection itself in the way that inferferon can be 'primed' in vitro. Mice surviving infections of more than I X LD100 as a result of poly C or poly I treatment show no protection against re-infection 15 days after the first infection, indicating no long-term stimulation of immune responses to the virus. Mice treated with an immunosuppressive regime of cytosine arabinoside can be protected against EMC virus infection with poly C and poly I treatment and athymic 'nude' mice can also be protected. The possibility of IgM stimulation by poly C and poly I seems unlikely from experiments in which serum was transferred from mice treated with the polynucleotides and an inactivated EMC 'vaccine' to recipient mice which were then challenged with infectious virus. Protection of mice against EMC virus by the single-stranded polynucleotides is abolished by administration of silica to the mice, implying an involvement of macrophages in the protective effects of poly C and poly I. The possibility that the polynucleotides stimulate clearance of virus particles, at least from immunologically responsive regions of the mouse, has been discounted by the inability of polynucleotide treatment to suppress 'vaccine' mediated protection of mice. These results indicate that macrophages are involved in the anti-viral effects of poly C and poly I either because they inhibit replication of the virus in macrophages or because direct anti-viral properties of macrophages are activated by the polynucleotides.

Animals↗