[Real-time PCR assay development for the control of vaccine against hemorrhagic fever with renal syndrome].

Introduction: Hemorrhagic fever with renal syndrome (HFRS) holds a leading place among natural focal human diseases in Russian Federation. There is no etiotropic therapy for the disease now. The vaccine prophylaxis is the most effective method to control this infection.

Human Diploid Fibroblast Cell Lines - a Model System for Studying Immunodulatory Properties of Modern Immunobiological Drugs and Viruses.

The immunomodulatory properties of immunobiological drugs Glutoxim and Phosprenyl we well as vesicular stomatitis virus and inactivated tick-borne encephalitis vaccine virus were studied using human diploid fibroblast cell line from the collection of M. P. Chumakov Federal Research Center for Research and Development of Immunobiological Products.

Selection of Domestic Cell Lines for the Creation of Diagnostic and Preventive Preparations against Enterovirus 71.

We studied the sensitivity of domestic proprietary human and animal cell lines from the collection of M. P. Chumakov Federal Scientific Center for Research and Development of Immuneand-Biological Products to infection with different enterovirus 71 strains.

[Antiviral activity and possible mechanisms of action of moraprenil phosphates during experimental infection caused by herpes simplex type 1 virus].

Aim: Study of antiviral activity of moraprenil phosphates (MPP) against herpes simplex type 1 virus (HSV1) in vitro and during experimental infection caused by HSV1 in mice.

Materials And Methods: Activity of MPP in vitro was tested by the ability to suppress formation of symplasts in VERO cells infected with HSV1, strain VR-3. A series of MPP that suppress virus-induced symplast-formation by 30 times was selected for in vivo experiments.

[Adjuvants in modern medicine and veterinary].

The review is dedicated to immunologic adjuvants--various natural and synthetics substances that are added to vaccines for stimulation of specific immune response, but they do not induce specific response themselves. Critically important is the selection of the correct adjuvants, for which mechanisms of effect on immune system are studied the most. The majority of these mechanisms as well as physical-chemical and biological features of modern adjuvants are analyzed in the review.

[Multidirectional effect of MIF and sodium polyprenyl phosphate on the course of experimental flavivirus infection in mice].

Aim: Study of macrophage migration inhibiting factor (MIF) effect after intracerebral administration on the course of experimental infection induced in mice by tick borne encephalitis virus (TEV), and study of sodium polyprenyl phosphate (PPP) and/or antibodies against MIF on the course of this infection against the background of MIF administration.

Materials And Methods: Phosprenil preparation was used as a source of PPP. PPP was administered intracerebrally.

[Experimental study of the phenomenon of antibody dependent tick-borne encephalitis virus infectivity enhancement in vitro].

Phenomenon of antibody dependent tick-borne encephalitis virus (TBEV) infectivity enhancement in the human monocytic cell culture J-96 has been studied. Three specific commercial sera that are generally used for therapy and prevention of TBE in humans were used. Results showed that enhancement of TBEV infectivity was markedly apparent following use of 2 out of 3 studied sera.

[Antiviral and immunomodulating activity of polyprenyl phosphates in viral infections].

Expressed antiviral activity of Fortepren (FP) and Gamapren (GP), polyprenyl phosphate (PPP)-contaning agents, was demonstrated in experiments on mice infected with the human herpes simplex virus, type 1 (HSV1) or the vernal encephalitis virus (VEV). Since both the viral infections are of great social significance, the PPP-containing agents should be considered prospective for the medical practice. The experimental data suggested that both the drugs considerably inhibited the VEV infectiousness in the susceptible cell culture.

Serum levels of interleukin 6 in recently hospitalized tick-borne encephalitis patients correlate with age, but not with disease outcome.

Infection with many encephalitic viruses is associated with the induction of the proinflammatory cytokine interleukin (IL)-6. In some situations, induction of high levels of this cytokine is associated with a protective response, but in others it can be linked to tissue damage and disease. In the studies reported here, levels of serum IL-6 and virus-specific antibodies were measured on admission to hospital and correlated with clinical outcomes.

[Moraprenylphosphates suppress reproduction of Taylor murine encephalomyelitis virus and accumulation of VP3 viral protein in susceptible cell cultures BHK-21 and P388D1].

Influence of moraprenylphosphates (phosphorylated polyprenol of plant origin) upon the accumulation of Taylor murine encephalomyelitis virus VP3 protein in the susceptible cell cultures was studied. It has been shown that moraprenylphosphates inhibited the accumulation of VP3 at early stages of infectious process. Moraprenylphosphates were found to decrease infectivity of the virus as well as virus-induced cellular apoptosis.

[Synthetic fragments of the NS1 protein of the tick-borne encephalitis virus exhibiting a protective effect].

Potentially immunoactive regions of the NS1 nonstructural protein of the tick-borne encephalitis virus that can stimulate the antibody formation in vivo and protect animals from this disease were chosen on the basis of theoretical calculations. Eleven 16- to 27-aa peptides containing the chosen regions were synthesized. The ability of the free peptides (without any high-molecular-mass carrier) to stimulate the production of antipeptide antibodies in mice of three lines and ensure the formation of protective immunity was studied.

[The correction action of Phosprenyl and Gamavit on the functional activity of mouse peritoneal macrophages in response to high doses of Staphylococcus aureus alpha-toxin].

The study of the functional activity of peritoneal macrophages of BALB/c mice at different stages of the toxic action caused by S. aureus alpha-toxin (ST) was carried out. The analysis of the dynamics of toxic reaction revealed the main critical points of triggering necrotic processes: the first hour and day 2.

A synthetic peptide based on the NS1 non-structural protein of tick-borne encephalitis virus induces a protective immune response against fatal encephalitis in an experimental animal model.

Linear immunogenic peptides corresponding to amino acid sequences from the NS1 non-structural protein from tick-borne encephalitis virus (strain Sophyin) were predicted using established algorithms and synthesized. Of the 12 peptides predicted, 11 were able to induce peptide-specific antibodies in BALB/c mice but only 1 of these 11 was able to induce antibodies, which reacted with the native protein in a radio-immune precipitation assay. This peptide corresponds to amino acids 37--55, and forms one of the predicted structurally conserved alpha helices of the virus NS1 protein.

Polyprenols as possible factors that determine an instructive role of the innate immunity in the acquired immune response.

Polyprenols are an integral part of all living cells including prokaryotic and eukaryotic ones. These compounds take part in biosynthesis of glycoproteins. We have found that phosphates of polyprenols may act as effective antiviral agents with a wide spectrum of activity.

Role of Cytokines in Immunomodulatory Effects of Polyprenyl Phosphate: New Generation of Antiviral Drugs.

Immunomodulatory properties of sodium polyprenyl phosphate (PP) were studied in vivo and in vitro. After injection to mice, PP was shown to increase serum levels of TNF-alpha, IL-6, and IFN-gamma. The simultaneous inoculation of tick-born encephalitis virus (TBEV) and PP to mice resulted in earlier serum appearance of IL-6, TNF-alpha and IFN-gamma (at days 1, 2 and 3, respectively) compared with mice which have received PP only.

[The preparation phosprenyl suppresses diarrhea and cattle infectious rhinotracheitis virus multiplication in sensitive cell cultures].

Fosprenil suppressed the multiplication of cattle diarrhea virus in calf coronary vessel cell culture. Added to the culture of infected cells in a dose of 200 mg, the drug decreased the virus titer 30-fold in comparison with infected control cultures. Antiviral activity of fosprenil towards infective rhinotracheitis virus multiplication was still higher: in a dose of 100 mg it decreased the virus titer in fetal calf lung culture 100-fold in comparison with the control.

[Protective effect of a new antiviral preparation of phosprenyl in experimental tick-borne encephalitis].

Antiviral activity of phosprenyl was studied in BALB/c mice infected with tick-borne encephalitis (TBE) virus. Up to 60% animals infected with TBE virus survived after 1-3 intramuscular injections of phosprenyl. The mortality in the untreated group infected with the virus was 100%.

[Stress increases the population of splenic macrophages, permissive for Langat virus, in mice].

As shown in experiments on BALB/c mice, stress caused by hypokinesia is associated with a 3- to 8-fold increase in the number of splenic macrophages, permissive to Langat virus. No changes in the proportion of T and B lymphocytes in the spleen of the animals occur under the influence of the stress. Simultaneously with an increase in the subpopulation of permissive splenic macrophages, the stressed mice have exhibited an increase in sensitivity to intraperitoneal infection with Langat virus.

Immunological basis for protection in a murine model of tick-borne encephalitis by a recombinant adenovirus carrying the gene encoding the NS1 non-structural protein.

The humoral immune response to flaviviruses is mainly directed to the major envelope protein, E, and a glycosylated non-structural protein, NS1. Cell-mediated immune responses, however, appear to be directed mainly against non-structural proteins. Experiments described here show that a defective recombinant adenovirus (Rad51) containing the gene encoding the NS1 protein of tick-borne encephalitis virus can induce a strong protective immune response against several pathogenic tick-borne flaviviruses in an experimental animal model, and can enhance the efficacy of conventional vaccine preparations.

[A recombinant adenovirus expressing the NS1 nonstructural protein of tick-borne encephalitis virus: some characteristics of the immunologic basis of antiviral action].

Recombinant adenovirus expressing NS1 nonstructural protein of trick-borne encephalitis (TBE) virus (Rad 51) protected mice from many strains of TBE and Omsk hemorhagic fever (OHF) viruses, but virtually did not protect them from Negishi virus. During combined use of whole-virion inactivated TBE vaccine and Rad 51 the recombinant adenovirus notably potentiated the protective effect of the traditional vaccine. The results of adaptive transfer of immunological material from mice infected with Rad 51 showed that both the vaccinated animals' sera and the pool of T and B cells partially protected the recipient mice from lethal TBE infection.

[An immunomodifier--staphylococcal anatoxin--prevents the development of immunosuppression caused by informational stress in mice].

The action of information stress for 14 days leads to the development of immunosuppression, which is manifested by the suppression of humoral response to sheep red blood cells (SRBC) and the decrease of resistance to Langat virus having low pathogenicity. As shown in this investigation, an immunomodifier, purified staphylococcal toxoid (PST), protects experimental animals from the immunosuppressive effect of information stress. After the injection of PST to stress-affected mice in doses of 15 or 1.

Phosprenyl: a novel drug with antiviral and immunomodulatory activity.

A novel antiviral drug with immunomodulatory activity (Phosprenyl) is presented. The main active ingredient of the preparation is polyprenyl phosphates. This medicine is highly efficient against a number of viruses, including HIV in vitro, and tick-borne encephalitis and rabies viruses in the experimental models in vivo.

[The effect of a persistent viral infection on natural antitumor resistance].

The influence of persistent infection with Tahyna virus on the natural antitumor resistance of the hosts was studied in mature mice. The infection was shown to suppress the host natural antitumor resistance. The development of infection was accompanied by a decrease of natural killer cell cytotoxicity against YAC-1 cell line within 7 days after virus inoculation.

Replication of Langat virus in immunocompetent cells of mice subjected to immobilization stress.

Immobilization stress (hypokinesis) in Balb/c mice may aggravate asymptomatic infection with Langat virus (strain TP-21) as evidenced by 4-fold increased lethality in comparison with control animals. The virus levels in the spleen and brain of stressed and infected mice and the in vitro yield of the virus in immunocompetent cells derived from stressed mice were significantly higher than in controls. Enhanced virus replication in latter cells may contribute to increased accumulation of the infectious agent in lymphatic tissues, which would facilitate virus invasion into CNS followed with acute disease and death of animals.

[Role of antigen-nonspecific suppressors occurring in stress in the pathogenesis of Langat virus infection in mice].

Stress factors of different nature activate antigen-nonspecific suppressors inhibiting different mechanisms of immune response in mice. The adoptive transfer of the population of immunocompetent cells containing stress-induced suppressors to mice infected with Langat virus has been found to lead to the activation of asymptomatic infection. The data obtained in this investigation indicate that the above-mentioned mechanism of the development of antigen-nonspecific immune deficiency is of importance in the pathogenesis of viral infections in man and it explains the onset of diseases (or their aggravation) under the conditions of stress.