[Combined antiviral effect of synthetic polyribonucleotide interferonogens and specific antiviral antibodies in arbovirus infections]. / Kombinirovannyi protivovirusnyi éffekt sinteticheskikh poliribonukleotidnykh interferonogenov i spetsificheskikh protivovirusnykh antitel pri arbovirusnykh infektsiiakh.

A model of tick-borne encephalitis in BALB/c mice was used to investigate the protective anti-viral effect of an interferon inducer, poly(G).poly(C), and specific gamma-globulin administered to the animals together or separately in small doses 24 hours before or after virus inoculation. Administration to the animals of poly(G).poly(C) alone or gamma-globulin alone was shown to produce a poor protective effect. Simultaneous administration of both preparations resulted in a significant decrease of mouse mortality after infection. As a result of the pretreatment of chick embryo cell cultures with poly(G).poly(C) before inoculation and the addition of specific immune serum to the agar overlay after the Sindbis virus inoculation, its multiplication was inhibited much more than after treatment of the cells with interferon inducer alone or antibody alone. Possible mechanisms of the observed additive antiviral effects of the interferon inducer and antibody, including those associated with the influence on the virus-induced interferon production, as well as the possibility of their combined use for the prevention and treatment of viral infections are discussed.

[Modification of the poly G-poly C complex by incorporation of adenosine in the purine chain]. / O modifikatsii kompleksa poli(G)-poli(Ts) vkliucheniem adenozina v purinovuiu nit'.

Antiviral and interferonogenic activity of the complexes of poly(G,A) . poly(C) and poly(G) . poly(C) was studied in mice and cell cultures. Three out of 4 complexes of poly(G,A) . poly(C) had insignificant antiviral and interferonogenic activity in chick embryo cells. One of the complexes induced low levels of interferon production in mice and decreased the rate of their death from experimental forest-spring encephalitis. The activity of poly(G) . poly(C) in the above cell systems was much more pronounced. Unlike this complex, some complexes of poly(G,A) . poly(C) showed a noticeable activity in the cells of Primates. The effect of the noncomplementary base in the purine thread of poly(G) . poly(C) on its biological activity and nucleotide composition is discussed.

[Induction of plant resistance to the tobacco mosaic virus with a double-stranded poly(G)-poly(C) complex]. / Induktsiia ustoichivosti rastenii k virusu tabachnoi mozaiki dvunitevym kompleksom poli(G)-poli(Ts).

Inoculation of double-stranded polyribonucleotide poly(G) . poly(C) complex in a concentration of 50-200 micrograms/mg into tobacco and thornapple leaves was found to produce resistance of the plants to subsequent infection with tobacco mosaic virus (TMV) manifested in decreased number and size of local virus lesions. The induced resistance may spread over the plant and be found in the upper untreated leaves. The level of systemic resistance, however, is much lower than that of the resistance demonstrated in the injected leaves. Actinomycin D (5 micrograms/ml) had no significant effect on the number but stimulated the growth of lesions developing in leaves injected with poly(G) . poly(C) as well as increased their number in the upper leaves of the same plants proximal to the treated ones. Development of tobacco resistance to TMV was accompanied by changes in the activity of terminal oxidases, particularly peroxidase. Possible mechanisms of formation of induced resistance are discussed.

[Comparison of reactivities or uridine- and cytidine-2',3'-cyclophosphates as donors and uridine and cytidine as acceptors of phosphate under dinucleoside monophosphate synthesis catalyzed by RNAase A]. / Sravenenie reaktsionnoi sposobnosti uridini tsitidin-2',3'-tsiklofosfata kakdonorov, uridina i tsitidina kak aktseptorov fosfata v sinteze dinukleozidmonofosfatov, kataliziruemom RNKazoi A.

In order to determine the relative activity of pyrimidine nucleoside-2',3'-cyclophosphates as donors and nucleosides as acceptors of phosphate in the reaction of the internucleotide bond formation catalyzed by RNAase A (EC 3.4.1.22), a comparative synthesis of dinucleoside monophosphates UpU, UpC, CpU and CpC at three different enzyme concentrations (20, 40 and 70 mkg/ml) and two temperatures (0 degrees and -15 degrees) was carried out. The conversion rate of donor (U greater than p and C greater than p) during the synthesis and in the competitive reaction of hydrolysis strongly depends on the type of acceptor activity as compared to uridine. Based on the data of synthesis and simultaneous hydrolysis of U greater than p and C greater than p it may be concluded that in the both cases the latter donor is more reactive. The approaches to the determination of the substrate activity of the donors and acceptors for the evaluation of optimal conditions of the dinucleoside monophosphate synthesis depending on the donor--acceptor combination are discussed.

[Acceptor activity of 4-N-acetylcytidine in the synthesis of (3'-5')-internucleotide bond catalyzed by pancreatic nuclease]. / Aktseptornaia aktivnost' 4-N-atsetiltsitidina v sinteze (3'-5')-mezhnykleotidnoi sviazi, kataliziruemom pankreaticheskoi ribonukleazoi

Cytidine and 4-N-acetylcytidine were compared as phosphate acceptors in dinucleoside monophosphate synthesis catalyzed by pancreatic ribonuclease with uridine-2',3'-cyclophosphate and cytidine-2',3'-cyclo phosphate as phosphate donors. Because of low solubility of 4-N-acetylcytidine in water, the synthesis was carried out in aqueus-organic media. The results obtained indicate that acetylation of the exoaminogroup of cytidine decreases its acceptor activity. For the first time uridilyl-(3'-5')-4-N-acetylcytidine and cytidilyl-(3'-5')-4-N-acetylcytidine are prepared enzymatically by pancreatic ribonuclease.

[Effect of interferon inducers on the development of specific resistance to tick-borne encephalitis]. / Vliianie induktorov interferona na formirovanie spetsificheskoi rezistentnosti k kleshchevomu éntsefalitu

Various natural and synthetic interferon inducers stimulate postvaccination immunity to tick-borne encephalitis virus in mice. This capacity was found not only in macromolecular synthetic polyribonucleotides such as (poly I)-(poly C), (poly G)-(poly C), (poly A)-(poly U) and substances with much lower molecular weight such as copolymers of vinylpyrrolidone with maleic anhydride, crotonic acid or metacrylic acid but also in a low molecular interferon inducer tiloron. These and other interferon inducers examined (endotoxin S-typhi, statolon) exhibited no parallelism between the intensity of their stimulating effect of immunogenesis and levels of interferon production induced in mice and the associated resistance to tick-borne encephalitis. The results indicate a possibliity of using various interferon inducers for stimulation of post-vaccination immunity to tick-borne encephalitis.

[Effect of temperature and concentrations of initial components on synthesis of internucleotide bond catalyzed by pancreatic ribonuclease]. / Vliianie temperatury i kontsentratsil iskhodnykh komponentov na sintez mezhnukleotidnoi sviazi, kataliziruemi pankreaticheskoi ribonukeazoi

The synthesis of cytidylyu-(3,-5,)-cytidine (CpC) catalyzed by pancreatic ribonuclease at 23 degrees, 0 degrees, and -15 degrees C in Tris-HCl-buffer was compared with that in aqueous propan-2-0. The data obtained show that the increase in the yield of oligonucleotides in aqueous buffer at -15 degrees, observed earlier is rather a result of the concentration change in the reaction mixture caused by the freezing of water than by a temperature fall from 0 to -15 degrees. A 4-fold increase in the initial concentrations of the substrates and ribonuclease with respect to the concentrations used earlier leads to the yield of CC in a homogeneous solution at 0 degrees close to is yield found in the frozen mixture at -15 degrees.

[Modification of pancreatic ribonuclease activity in complexes with polyanions].

Carboxymethylcellulose, carboxymethylchitin, sulfoethylcellulose and dextrane sulfate interact with pancreatic ribonuclease. In comparison with ribonuclease activity the activity of formed complexes changes differently at the stages of transesterification and hydrolysis, and at each stage the effect of polymers on ribonuclease activity essentially differs. The use of ribonuclease-dextrane sulfate complex in the reaction of uridylyl-(3' leads to 5')-cytidine synthesis demonstrated that the protein synthetic activity completely retained when hydrolytic activity was considerably suppressed.

Double-stranded complex of polyguanylic and polycytidylic acids and its antiviral activity in tissue culture.

The antiviral activity and conditions of formation of the most active double-stranded complexes of synthetic homopolynucleotides, polyriboguanylic and polyribocytidylic acids, were studied on the model of primary trypsinized chick embryo cells and RNA-containing viruses. The (poly G).(poly C) complex was very active against the viruses tested; their replication in cell cultures was inhibited completely. The antiviral activity of the (poly G).(poly C) complex increased markedly in the presence of diethylaminoethyl- (DEAE-) dextran. After treatment with 1 mug/ml of (poly G). (poly C) for 1 hour in the presence of 100 mug/ml DEAE-dextran, the cell sheet remained protected for 5-7 days. Preparations of (poly G).(poly C) obtained under optimal conditions were as active as (poly I).(poly C) complexes and exceeded them markedly in the level of the therapeutic index which under the present experimental conditions was 5-10 times 10(3) for (poly G).(poly C). Highly purified homopolymers with sufficiently high molecular weight must be used for production of active and stable (poly G).(poly C) complexes.