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N Stebbing

Publications and source records attributed to N Stebbing.

16 recordsLinked to original sources
PubMed1979

Protection of mice against infection with wild-type Mengo virus and an interferon sensitive mutant (IS-1) by polynucleotides and interferons.

Single-stranded polynucleotide preparations [tRNA, poly(rI) plus poly(ho5C)-copolymer] which protect mice against picornavirus infections without inducing interferon, protected mice equally against infection with an interferon-sensitive mutant (IS-1) of Mengo virus and with wild-type virus (IS+). Poly(rI) . poly(rC), and mouse macrophage interferon [i.e. serum from mice treated with poly(rI) . poly(rC)] protected mice equally against infections with the two viruses, but fibroblast interferon protected better against infection with the interferon-sensitive mutant than with the wild-type virus. These and other results indicate that: Mengo virus had a genetic locus affecting sensitivity to fibroblast but not macrophage interferon; these two types of interferon have different mechanisms of action against Mengo virus infections in mice; Mengo virus genes controlling sensitivity to fibroblast interferon may modulate disease since infection in vivo induces only fibroblast interferon; the antiviral activity of the single-stranded polynucleotides is unlikely to be mediated by induction of either macrophage or fibroblast interferon.

Animals↗
PubMed1979

Absence of significant antiviral effects of beta-gamma-methylene GTP on encephalomyocarditis virus infection of L cells and mice.

The protein synthesis inhibitor beta-gamma-methylene guanosine triphosphate (Gpp-CH2p) is shown here to be ineffective as a 'leaky membrane' antiviral agent against encephalomyocarditis virus infection of L cells and mice. Studies with GppCH2p in encephalomyocarditis virus-infected L cells indicate that the cells only become permeable to the inhibitor late in infection because the compound significantly inhibits protein synthesis only when added at 4 h p.i. At this time 50 to 70% of the new infectious virus particles have already been synthesized, and this is reflected in maximum inhibition of virus yields of only about 40%. Moreover, comparison of inhibition of protein synthesis by GppCH2p in vitro and in cell cultures indicates that the intracellular concentration attained is only 0.25% of that in the medium. The lack of antiviral activity of GppCH2p in encephalomyocarditis virus-infected mice is probably due to leakiness of infected cells occurring too late for sufficient inhibition of virus synthesis to be obtained.

Animals↗
PubMed1978

Requirement for macrophages for interferon to be effective against encephalomyocarditis virus infection of mice.

Suppression of macrophages in mice by treatments with silica or auro-thiomalate (Myocrisin) reduced production of serum interferon by polyriboinosinic acid:polyribocytidylic acid by 85 to 90%, indicating that this double-stranded polynucleotide caused interferon production primarily in macrophages. Suppression of macrophages in mice by silica or Myocrisin treatment did not significantly affect the susceptibility of mice to encephalomyocarditis virus, although at virus doses around 20 times the 50% lethal dose they died about 48 h earlier. Macrophage interferon protected mice from encephalomyocarditis virus infection at much lower doses than fibroblast interferon, and treatment of mice with silica or Myocrisin abolished the protection conferred by macrophage interferon, whereas these treatments had a much smaller effect on the protection afforded by fibroblast interferon. The requirement for macrophages for interferon to be effective in mice can explain why macrophage suppression can cause normally nonlethal viruses to kill adult mice.

Animals↗
PubMed1977

Aminoacylation of encephalomyocarditis virus RNA.

RNA extracted from purified encephalomyocarditis (EMC) virus (EMC-RNA) can be aminoacylated with synthetase praparations from Escherichia coli, beef and rabbit liver. The extent of aminoacylation is between 0-024 and 0-080 moles per mole EMC-RNA and occurs only with serine. Either removal of possible low mol. wt. contaminants with 3 M-sodium acetate nor periodate oxidation of the virus RNA affects its aminoacylation capacity.

Amino Acids↗
PubMed1977

Protection of mice against encephalomyocarditis virus infection by preparations of transfer RNA.

Preparations of bacterial transfer RNA (tRNA), give dose-dependent protection of mice against encephalomyocarditis (EMC) virus infection at up to I mg tRNA per mouse with maximum response when the tRNA is administered around 6 h before infection. Protection occurs with intraperitoneally and intravenously administered tRNA against infections by both these routes. In some experiments significant protection occurs by single treatments of tRNA up to 24 h after infection with virus doses of I X LD100. Some tRNA preparations of eukaryotic origin do not give significant protection. Protection is not a feature of all species of bacterial tRNA; partially purified valine, tyrosine and phenylalanine tRNAs from Escherichia coli are not protective. tRNA treatment does not induce circulating interferon nor does it 'hypo-reactivate' the protective effect of poly (I).poly (C) treatment of mice. Humoral and cell mediated immune responses do not seem to be involved in tRNA mediated protection since first, cytosine arabinoside treatment does not affect protection by tRNA; second, serum from mice treated with tRNA and an EMC vaccine does not protect other mice against infection, and third, mice that survive normally lethal infections as a result of tRNA treatment are generally just as susceptible to re-infection as previously untreated, uninfected mice. Silica treatment abolishes protection of mice by tRNA implying that macrophages are necessary. However, tRNA does not seem to act by clearance of virus particles since vaccination of mice by inactivated EMC virus is not affected by tRNA treatment. These results are considered in relation to the presence of a tRNA-like structure in EMC virus RNA and protection of mice by other single stranded polynucleotides.

Animals↗
PubMed1977

Protection of mice against encephalomyocarditis virus infection by chemically modified transfer RNAs.

Periodate or nitrous acid treatment greatly decreases the ability of unfractionated Escherichia coli transfer RNA (tRNA) to be aminoacylated by tRNA-synthetases but these treatments do not affect their antiviral activity against encephalomyocarditis virus infection of mice. Bisulphite treatment of E. coli tRNA reduces its ability to be aminoacylated by 20% and has no effect on antiviral activity. Bromine water treatment of tRNA under conditions causing extensive base modifications eliminates aminoacylation and the antiviral activity of E. coli tRNA. Periodate treatment of yeast tRNA does not affect its antiviral activity and nitrous acid treatment increases its antiviral activity to that of E. coli tRNA. The ability to be aminoacylated does not therefore appear to be essential for antiviral activity of tRNA but extensive modification (bromine water treatment) does destroy antiviral activity.

Acylation↗
PubMed1976

Structural features of encephalomyocarditis virus RNA from analysis of reverse transcription products.

The presence in encephalomyocarditis (EMC) virus RNA of homonucleotide tracts 10 nucleotides or more in length has been investigated by testing the ability of homo-oligodeoxynucleotides to prime DNA synthesis in the reverse transcriptase from avian myeloblastosis virus. Neither (dC)10 nor (dA)10 promoted incorporation of [3H]deoxynucleotides into acid-insoluble material but (dG)10 and (dT)12-18 were effective primers and produced DNA products approximately 2000 nucleotides in length. We conclude that there are single-stranded oligo(rC) and oligo(rA) tracts in native EMC virus RNA at 37 degrees C. Kinetic analysis indicated that oligo(dT) priming is similar to priming on ovalbumin mRNA and that it gives rise to only one DNA product per template molecule. Oligo(dG) priming appears to be complicated by self-aggregation of the primer. Oligo(dT)-primed and oligo(dG)-primed DNA have both been separated on alkaline-sucrose gradients into two peaks of which only the 'heavier' will hybridise to EMC virus RNA. Competitive hybridisation experiments indicate that the 'heavy' oligo(dT)-primed and oligo(dG)-primed DNA fractions hybridise to overlapping sequences of EMC virus RNA and place the priming regions of EMC virus RNA approximately 500 nucleotides apart during reverse transcription.

Encephalomyocarditis virus↗
PubMed1976

Anti-viral activity against encephalomyocarditis virus and Semliki Forest virus and acute toxicity of poly I and poly C administered sequentially to mice.

Mice are protected against lethal intraperitoneal and intravenous infection by encephalomyocarditis virus and Semliki Forest virus by sequential treatment with poly I followed by either polyC or poly5-hydroxyC without production of interferon when the treatments are 4 or more hours apart and by the intraperitoneal or intravenous routes. Maximum protection occurs around 4 hours before infection and is still significant 20 hours after infection. Treatments with combinations of other homoribopolynucleotides were not found to be anti-viral. Protection by sequential polyI, polyC treatment of mice is relatively short-lived and does not 'hypo-reactivate' the protective effect of polyI:C and shows approximately half the protective effect of polyI:C. The toxicity of sequential polyI, polyC treatment is lower than that of polyI:C particularly if poly5-hydroxyC is substituted for polyC. Silica treatment of mice indicates that stationary macrophages are required for protection by polyI followed by polyC but an effect on humoral or cell mediated immune responses does not appear to be involved. The effect appears to be a synergism between the protection conferred by polyI or polyC alone.

Animals↗
PubMed1976

Anti-viral activity of single-stranded homopolynucleotides against encephalomyocarditis virus and Semliki Forest virus in adult mice without interferon induction.

Single administrations of poly C or poly I are anti-viral against infections of encephalomyocarditis (EMC) and Semliki Forest virus (SFV) in mice but poly U and poly A are not. The degree of protection is dose-dependent and mice which die do so at a later time when untreated controls even in a strain of mouse in which the time of death is not dependent on the dose of virus given. No circulating interferon is found after treating mice with poly C or poly I even at polynucleotide doses which give the same degree of protection as the interferon inducer, poly I:C. Several additional features distinguish the protection by poly C and poly I from interferon induction: the effect is low 24h before infection and maximal 6 h before infection, the effect is short-lived and mice do not show hypo-reactivation to repeated treatment. Limited treatment of mice with poly I:C, interferon or poly C before infection itself results in additional protection when poly C is also administered after infection, indicating that poly C has an effect after onset of virus replication. After infection poly C and poly I are both more effective by the intravenous route but before infection they are most effective when administered by the same route as the virus. Quantitative comparisons of the protective effects of poly C, poly I and the interferon inducer, poly I:C, are possible from dose response curves of the polynucleotides at different times relative to infection and by different routes of administration. The results are considered in relation to the presence of homopolyribonucleotide tracts in the viral genomes and effects on the reticulo-endothelial system of the mice.

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↗