[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. Anti-viral activity of MPP in vivo was studied in HSV-1 infected mice after administration of either prophylaxis or therapy regimens. RESULTS: MPP at the dose of 20 microg/mice during s/c administration exhibited a pronounced prophylactic-therapeutic effect. Effectiveness of MPP during clinically evident herpes against the background of developing neurologic symptoms was demonstrated for the first time. Visual observation of the mice, that had received MPP as the first clinical symptoms of the disease appeared, has shown that against the background of preparation injection the clinical signs have ceased after 2 - 3 days and did not registered at least for the whole duration of the observation period (14 days). CONCLUSION: Active herpes infection is accompanied by the increase of FoxP3 expression in-thymus was shown. Possible mechanisms of anti-viral effect of MPP are discussed.

[The preparation phosprenyl suppresses diarrhea and cattle infectious rhinotracheitis virus multiplication in sensitive cell cultures]. / Preparat fosprenyl podavliaet razmnozhenie virusov diarei i infektsionnogo rinotrakheita krupnogo rogatogo skota v chuvstvitel'nykh kul'turakh kletok.

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. Moreover, the cytopathogenic effects of the viruses in infected cultures were 24-48 h delayed under the effect of fosprenil in comparison with infected control cultures. These results recommend fosprenil for the treatment of cattle viral diseases.

[Protective effect of a new antiviral preparation of phosprenyl in experimental tick-borne encephalitis]. / Zashchitnoe deistvie novogo protivovirusnogo preparata fosprenil pri éksperimental'nom kleshchevom éntsefalite.

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%. Direct antiviral effect of phosprenyl was studied in sensitive SPEV cells infected with TBE virus. The titer of the virus decreased 10-fold in the cells treated with the drug vs. untreated control cells. Phosprenyl stimulates some interleukins: gamma-interferon, tumor necrosis factor-alpha, and interleukin-6. The stimulating effect of the drug manifests in intact animals and in those infected with TBE virus and treated with phosprenyl. The prospects of further trials of the drug as a therapeutic and prophylactic agent in TBE are discussed.

[The effect of Mycoplasma arthritidis superantigen on immunogenesis in transplacental infection]. / Vliianie superantigena Mycoplasma arthritidis na immunogenez pri transplatsentarnom infitsirovanii.

The immune responsiveness of the progeny of BALB/c mice, responsive to M. arthritidis superantigen (MAS), and C57BL/6 mice, nonresponsive to MAS, infected with M. arthritidis during the second half of pregnancy was studied. The investigation revealed that in responsive animals the proliferative response of spleen cells to MAS was suppressed with the level of response to concanavalin A remaining unchanged. The spleen cells of the test mice reacted to syngenic intact cells as to xenogenic ones and suppressed reaction to MAS and the production of interleukin 1 in the culture of spleen cells taken from the intact syngenic animals. The data obtained in this study suggest that after the infection of pregnant BALB/c mice with M. arthritidis immune tolerance to MAS developed in their progeny, which was accompanied by the induction of suppressor cells inhibiting the production of interleukin 1.

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 protective immune response against a lethal virus challenge can also be induced by the passive transfer of antibodies, B cells or T cells from animals vaccinated with Rad51. Raised levels of non-neutralizing antibodies and cytokines associated with a T helper cell-type 1 immune response are also observed. These data demonstrate the importance of non-structural viral proteins in the protective immune response against flaviviruses and support the use of non-structural viral proteins as vaccine components.

[The immunological consequences of congenital infections]. / Immunologicheskie posledstviia vrozhdennykh infekstii.

Mice of different strains were inoculated with type A influenza virus or Mycoplasma arthritidis in the second half of pregnancy. A part of the animals born after this inoculation were characterized by a sharp retardation of growth. The study of the immune status of such animals revealed that their proliferative response to mitogenic/superantigenic factors of the infective agents introduced during pregnancy was suppressed or absent, and the cells of their immune system began to recognize syngeneic intact stimulators in the mixed lymphocytes culture as heterogeneous ones. The spleen of the experimental animals was found to contain suppressor cells, both specific and nonspecific with respect to the infective agent. After inoculation with M. arthritidis areactivity was observed only in mice, sensitive to mycoplasmal superantigen. The data thus obtained suggest that the penetration of infecting agents producing mitogenic/superantigenic factors induced changes in the immune system, contributing to the persistence of the infective agent in the host body.

The Possible Immunological Mechanisms of Pathology in Mice with Congenitally Acquired Influenza Infection.

The fact that congenitally acquired viral infection often strongly influences specific and non-specific immunoreactivity is well documented. Viral infection of pregnant female may lead to serious of pathological consequences for the offspring, namely, to mortality, developmental disorders and in less severe cases to body growth retardation, wasting syndrome and immunodeficiency. In this connection, we have studied congenitally acquired influenza infection in CII mice. The progeny of C57BL/6 female mice, which were infected with influenza virus (A/WSN) by the 3rd week of pregnancy, exhibited a profound growth retardation and major morphological lesions of central nervous system, lymphoid and other organs. We have found out that mice with congenitally acquired influenza infection had autoreactive killer T cells in their lymphoid organs. CII mice exhibited some features of chronic immune activation, namely elevated spontaneous proliferation, spontaneous development of plaque forming cells, and spontaneous inhibition of migration activity. Lymphoid cells from mice with congenitally acquired influenza infection induced an enlargement of regional lymph nodes after they had been injected into syngeneic non-infected recipient in popleteal node assay. The level of this reaction depended on the level of virus-bearing cells in donor cell population and correlated with the increase of gammadelta and CD4(+) T cells. The role of these interactions in pathology is discussed herein.

[The effect of immunomodulating doses of purified staphylococcal anatoxin on the spontaneous and mitogen-induced proliferation of mouse splenocytes]. / Vliianie immunomoduliruiushchikh doz anatoksina stafilokokkovogo ochishchennogo na spontannuiu i mitogenindutsirovannuiu proliferatsiiu splenotsitov myshei.

Purified staphylococcal toxoid (PST) was shown to alter the spontaneous and mitogen-induced proliferation of mouse spleen cells. In vitro, PST inhibited spontaneous proliferation, as well as proliferation induced by the optimal dose of Con A (2 micrograms/ml) and the optimal and suboptimal doses of lipopolysaccharide (LPS) (100 and 50 micrograms/ml). At the same time the dose of 1.5 binding units (BU) of PST, inhibiting spontaneous proliferation in vitro, induced strong proliferative response in combination with the suboptimal dose of Con A (1 microgram/ml). Our experiments demonstrated that the spontaneous proliferation of mouse spleen cells, immunized with the toxoid, remained unchanged (0, 15 or 15 BU/mouse) or increased (1.5 BU/mouse) the response of spleen cells of immune animals to ConA and LPS also changed in comparison with the control, depending on the conditions of the experiment. After the use of the combination of 2 micrograms of Con A and 1.5 BU of PST or 100 (50) micrograms of LPS and 1.5 BU of PST the inhibition of proliferative response was observed. The summation of the signals of the suboptimal dose of Con A (1 microgram) 1.5 BU of PST was demonstrated.

[A recombinant adenovirus expressing the NS1 nonstructural protein of tick-borne encephalitis virus: some characteristics of the immunologic basis of antiviral action]. / Rekombinantnyi adenovirus, ékspressiruiushchii nestrukturnyi belok virusa kleshchevogo éntsefalita NS1: nekotorye kharakteristiki immunologicheskikh osnov protivovirusnogo deistviia.

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. NS1 protein expressed by adenovirus increased the level of the key interleukins (IL) interferon, tumor necrosis factor, IL-1 beta, IL-2, and, probably, IL-4. Vaccination of mice with Rad 51 resulted in the appearance of antibodies to NS1 protein in rather high titers. The prospects of using Rad 51 as a vaccine against TBE are discussed.

[The immunogenic and protective properties of the cell wall proteins of Listeria monocytogenes]. / Immunogennye i protektivnye svoistva belkov keltochnoi stenki Listeria monocytogenes.

Two protein antigens with molecular weights of 58 kD (antigen Lm58) and 79/39 kD (antigen Lm79/ 39) were isolated from Listeria monocytogenes cell wall. Only Lm79/39 was shown to protect mice from L. monocytogenes infection, increasing their LD50 and survival time. The protective activity of Lm79/39 correlated (r = 0.64) with its mitogenic properties and its capacity for activating the production of interleukin-1- and interleukin-2-like factors. More over Lm79/ 39 induced more strong than Lm58 specific lymphocyte proliferation. The two antigens had practically no difference in their capacity for cytotoxic cell activation. The protective activity of Lm79/39 is probably linked with its immunomodulating properties, which opens a perspective for its use as a component of an antilisteriosis vaccine.

[The use of T-activin for the prevention of congenital influenzal infection in mice and the correction of the immune deficiency]. / Ispol'zovanie T-aktivina dlia profilaktiki vrozhdennoi grippoznoi infektsii u myshei i korrektsii immunodefitsita.

Viremia accompanying influenza infection and the possibility of transplacental passage of the virus into the fetus make it expedient to develop measures for the prophylaxis of intrauterine infection of the fetus in case of influenza during pregnancy. The work presents the optimum scheme of administration of T-activin for prophylactic purposes to pregnant mice with acute influenza infection. Besides, the use of T-activin for immunocorrection in case of established congenital influenza infection in mice is proposed.

[The role of suppressor cells in congenital influenza infection in mice]. / Rol' supressornykh kletok pri vrozhdennoi gippoznoi infektsii u myshei.

Young mice with congenital influenza infection have lower immune responsiveness of lymphocytes to nonspecific mitogens and influenza virus antigens. Lymphocytes of such animals inhibit proliferation of normal lymphoid cells activated with concanavalin A and immune lymphocytes activated with influenza virus antigens. It is assumed that in congenital influenza infection one of the possible mechanisms of immunosuppression in mice is the activation of suppressor T-cells.