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Introduction: The persistence of immune dysfunction during therapy has serious consequences for the health of HIV-infected people. Therefore, an important direction is the search for drugs that can reduce the inflammatory potential of the immune system and serve as an additional component of antiviral therapy. Aim ‒ to study the effect of the immunomodulatory drug Sodium deoxyribonucleate with iron complex (DNA-Na-Fe) on the expression of activation markers in MT-4 cells infected with HIV-1., Materials and Methods: Expression levels of CD4, CD28, CD38, CD62L and HLA-DR proteins on the plasma membrane were measured in cells. To assess viral activity, the p24 protein was quantified by ELISA., Results and Discussion: The two cell variants with different replicative activity were analyzed. Control cells, cells with DNA-Na-Fe, infected cells and infected cells with DNA-Na-Fe were tested. Based on the results obtained, it can be concluded that antiviral activity of the drug in MT-4 cells infected with HIV-1 is associated with immunomodulatory activity that enhances the expression of membrane proteins CD4, CD28, CD38 and CD62L. Diversity in the effect of DNA-Na-Fe on the studied surface proteins expression in two cell lines indicates that they depend on the characteristics of the combined molecular biological processes occurring in cells. And the increased effects observed in a system with changes in replicative activity assumes its active participation in virus replication at the stages of virus penetration and budding., Conclusion: Studies have shown that DNA-Na-Fe has antiviral and immunomodulatory activity.

Introduction: The urgent problem of modern medicine is the fight against acute respiratory viral infections (ARVI). To combat ARVI, drugs of wide antiviral potency are needed, as well as immunomodulating drugs. Such antiviral and immunomodulatory effects has sodium deoxyribonucleate (DNA-Na) and its complex with iron (DNA-Na-Fe) developed on the basis of double-stranded DNA of natural origin., Aim of the Study: To assess antiviral and virucidal activity of DNA-Na and DNA-Na-Fe against viruses of different kingdoms and families., Materials and Methods: Antiviral and virucidal activity of DNA-Na and DNA-Na-Fe was assessed in cell cultures infected with viruses., Results and Discussion: DNA-Na and DNA-Na-Fe had antiviral activity against adenovirus at concentrations of 2501000 mcg/ml. Antiviral effect of both drugs was not detected in case of poliovirus. DNA-Na and DNA-Na-Fe had antiviral activity against coronavirus in all administration schemes. EC50 for DNA-Na ~ 2500 mcg/ml, for DNA-Na-Fe ~ 1000 mcg/ml. In cells treated with DNA-Na-Fe, secretion of following proinflammatory cytokines was detected: Interleukin (IL) 1, IL-2, IL-6, IL-18, interferon- (IFN-), IFN-, as well as anti-inflammatory cytokines: IL-4, IL-10, antagonist of IL-1 receptor. Evidently, DNA-Na and DNA-Na-Fe have antiviral effect, but mechanism of action does not seem to be associated with specific effect on viral replication. Presence of virucidal activity of drugs against representatives of Coronaviridae, Adenoviridae, Picornaviridae, Retroviridae, Herpesviridae in vitro test in range of 1.03.0 lg TCID50 was identified., Conclusion: Presence of simultaneous antiviral and virucidal activity of DNA-Na and DNA-Na-Fe against adeno- and coronaviruses shows their prospects for prevention and treatment of ARVI.

Introduction: The important role of integrins (IG) in the initiation and development of cancer processes makes these structures convenient targets for the development of immunomodulatory therapeutic drugs that have an effect directly on these molecules. Among the latter, IG β1, α4 and cell adhesion receptor ICAM-1 (intercellular adhesion molecule 1) are of particular interest. Immunomodulators are capable of changing the IG activity through non-specific mechanisms, which, however, in some cases can cause a decrease in the protective functions of the immune system and health deterioration.The aim of the study was to determine the effect on the levels of cellular expression and the nature of IG metabolism of the drug sodium deoxyribonucleate with ferrum complex, DNA-Na-Fe, which is having been used in the Russian Federation as an immunomodulatory agent, but whose action has not been studied in details so far., Material and Methods: We used 2 variants of the neoplastic CD4+ T-lymphocyte cell line transformed with human T-lymphotropic virus type 1 (HTLV-1) of the Retroviridae family, MT-4 (MT-4/1 and MT-4/2). The indicated variants were characterized by different levels of expression of the protein activation markers CD28 and CD38. After cell culture in the presence of 500 μg/ml DNA-Na-Fe, the expression levels of IG β1 (CD29), α4 (CD49d), and ICAM-1 (CD54) were studied by flow cytometry., Results: The cells of the both lines contained many membrane proteins CD29+ (90.4% ± 4.5) and CD54+ (97.9% ± 1.4), while small percentage of cells contained protein CD49d+ (1.9% ± 1.0). No changes in the expression of the studied proteins were observed in the presence of the drug., Discussion: The levels of IG β1, α4 and ICAM-1 expression may serve as one of the phenotypic characteristics of MT-4 cells. The obtained data are of great importance because the peculiarities of CD4+ T-lymphocytes transformation and their metabolism during HTLV-1 infection have not been sufficiently studied so far., Conclusion: The results of this work may be helpful in determining the pathogenesis of HTLV-1-induced diseases, some types of malignancies, and in searching for new specific pharmacological agents, including molecularly targeted ones. The results of the study will help to expand the existing knowledge on the markers of MT-4 cell line.

The combined action of the immunostimulatory drug Stimforte and the basic etiotropic drug acyclovir commonly used to treat herpes infections was studied using the model of lethal experimental infection of mice BALB/c with herpes simplex virus type 1. It was found that the interaction of these drugs is additive. In addition, Stimforte inhibits infection caused by a strain of virus, which is highly resistant to acyclovir. When administered 24 hours prior to HIV-1 infection of human lymphoblastoid cells MT-4, Stimforte exhibited reliable antiretroviral activity best expressed during the early period of infection (the 3rd day). On the 6th day of observation the effect was almost completely lost. Combined use of Stimforte at a dose of 50-100 µg/ml with a subthreshold dose of retrovir (0.03 µg/ml) had a synergistic antiviral effect. Thus, Stimforte, which exhibits, on the one hand, antiviral activity against viruses of different families and, on the other hand, the immunomodulatory properties, could be promising as an etiopathogenic tool in helping to normalize both nonspecific and specific immunity. It may be used simultaneously with etiotropic antiviral chemotherapy in treatment of generalized herpes infection in patients with immunodeficiency. Furthermore, Stimforte can be used in the case of development of drug resistance in HSV, in particular, in HIV-infected patients.

In this work the proinflammatory (IL-1β, IFN-γ, TNF-α, IL-2) and anti-inflammatory (IL-4, IL-10) plasma cytokine levels were evaluated in HIV-infected patients with or without antiretroviral treatment (ART). IFN-γ was detected in 94% samples with and without ART, TNF-α in 88% and IL-2 in 38% samples without ART, as well as in 12% and 30% samples with ART, respectively. Positive correlation was detected between viral RNA and IFN-γ levels (rs = 0.13) and negative correlation (rs = -0.242) in the patients without or with ART. Cosecretion of three cytokines (IFN-γ, TNF-α, IL-2) was detected in 31% samples and two cytokines (IFN-γ, TNF-α) in 35% samples of persons without ART. Cosecretion of three cytokines (IFN-γ, TNF-α, IL-2) was detected in 20% samples with ART; cosecretion of IFN-γ and IL-2 was detected in 10% samples. The higher percentage of the proinflammatory cytokines with cosecretion was detected in plasma HIV-infected patients without ART in the course of 6 and more years, which suggests that their immune system is able to provide disease control.

Fractions of aqueous and water-alcohol extracts of the birch fungus Inonotus obliquus have antiviral effect against the human immunodeficiency virus type 1 (HIV-1). Antiviral properties of low toxic extracts were manifested in the concentration of 5.0 μg/ml upon simultaneous application with the virus in the lymphoblastoid cells culture MT-4. The extract of the birch fungus can be used for development of new antiviral drugs, inhibitors of HIV-replication when used both in the form of individual drugs and as a part of complex therapy.

The antiretroviral properties of Fullevir (sodium salt of fullerenepolyhydropolyaminocaproic acid) manufactured by IntelFarm Co.) were studied in the human cell culture infected with human immunodeficiency virus (HIV). The agent was ascertained to be able to protect the cell from the cytopathic action of HIV. The 90% effective concentration (EF90) was 5 microg/ml. The 50% average toxic concentration was 400 microg/ml. Testing of different (preventive and therapeutic) Fullevir dosage regimens has shown that the drug is effective when used both an hour before and an hour after infection and when administered simultaneously with cell infection. The longer contact time for the agent with the cells increased the degree of antiviral defense. Co-administration of Fullevir and the HIV reverse transcriptase inhibitor Retrovir (azidothymidine) showed a synergistic antiretroviral effect. Thus, Fullevir may be regarded as a new promising antiretroviral drug for the treatment of HIV infection.

Two groups of the antiviral agents: 1) adamantane- and norbornen-containing compounds with in-built cholesterol to potentiate the membranotropic properties and 2) synthetic matrix protein peptides (peptides A and B) were found to have effects on HIV replication. The agents of the former group produced antiviral activity only when added in combination with the virus. Peptide A (matrix protein 43-60 amino acids) inhibited viral replication when added in both the early and late periods. Fluorescein-labeled peptide A was detectable in the cytoplasm and nucleus (although adsorption of a portion of the peptides cannot be excluded onto the cell surface). Peptide A was shown to inhibit Gag precursor p55 transport from the nuclei to the plasma membrane, the site of virus assembly. Peptide B had no antiviral activity.

Ferrovir (trivalent iron in complex with native sturgeon milt DNA) is nontoxic, its 50% inhibiting concentration (IC50) is at least 4000 micrograms/ml, 90% effective concentration (EC90) towards HIV-1 is 800 micrograms/ml. These effects do not depend on the cell culture or individual biological characteristics and subtypes of 7 strains of HIV-1 used in our study. The chemotherapeutic index of the drug is more than 20. Combined therapy with ferrovir and retrovir had an additive antiviral effect. Ferrovir reduced the titer of human CMV in fibroblast culture by 1-2 Ig TCD50. Ferrovir protected mice after intracerebral inoculation with lethal herpes simplex virus (type 1) (survival 33.7%, protection 27.1%, which is close to the reference group treated with zovirax). These facts evidence antiviral activity of ferrovir towards RNA and DNA viruses and prompt further study of this drug with the aim of its clinical application.

Cell systems infected with 63 strains of types 1 and 2 HIV virus (HIV-1 and HIV-2) were examined under electron microscope. HIV virions were most frequently detected near the cell membrane or budding from it. In the cytoplasm HIV occurred only in vacuole-like formations. Accumulations of mature virions were seen in the cell-to-cell space. Mature particles of HIV-1 and HIV-2 differed by their morphology from oncoviral C particles and were similar rater to the Visna/Medi type Lentiviruses. Morphological analysis of HIV strains isolated in Russia demonstrated their similarity to be foreign HIV strains.

The anti-HIV activity of an antiseptic miramistin in the presence of fetal calf serum (FCS) was studied. It has been recently shown that cation detergent miramistin at a concentration of 100 micrograms/ml prevented HIV-1 replication in MT-4 cells when these cells were cocultivated with MT-4 cells previously infected and treated with the detergent in a protein-free medium. Under such conditions 50 micrograms of miramistin per ml delayed HIV propagation in MT-4 cells by 14 days. Detergent-dependent arrest of HIV development was abolished by addition of FCS at a final concentration of 50%. Miramistin in a dose of 100 micrograms/ml prevents HIV-1 replication in Jurkat-tat cells when they are cocultivated with the cells of the same line previously infected and treated by the detergent in the presence of 5% FCS. FCS in concentrations from 12.5 to 75% prevents the anti-HIV activity of miramistin in a dose of 100 micrograms/ml.

The anti-HIV activity of a cationic detergent myramistin and nonionic detergent dezintegron-0 (d-0) was studied using HIV-1 strains III B/H9 and BRU in lymphoblastoid cells MT-4 and Jurkat-tat. Myramistin in a concentration of 0.075 mg/ml was shown to prevent HIV-1 replication in MT-4 when these cells were cocultivated with the cells preinfected and treated with the detergent. Myramistin in concentrations from 0.030 to 0.050 mg/ml delayed the accumulation of virus antigens in the cells by 4 and 14 days, respectively, without preventing the infection of intact cells. Nonionic d-0 prevented HIV-1 infection of intact Jurkat-tat cells at a concentration of 12.5 mg/ml.

Fifty-seven HIV-1 strains were isolated from peripheral blood lymphocytes of 102 HIV-infected persons involved in epidemic outbreaks in different cities of the USSR. The effectiveness of isolation was 29.1% in asymptomatic infection, 51.7% in cases with generalized lymphadenopathy, and 82.6% in persons with severe clinical manifestations. Identification of the isolates by indirect immunofluorescence, ELISA, reverse transcriptase activity, Western blot, electron microscopy, and polymerase chain reaction showed them to belong to HIV-1 type. Reproduction of the isolates in cell cultures was accompanied by cytopathic effect and syncytium formation. The isolated strains can be divided into two groups: (1) the poorly growing isolates with low or negative RT and ELISA results and (2) the isolates with high infectivity, broad spectrum of cell tropism, and high levels of RT and ELISA. These data show the correlation of biological properties of HIV-1 strains isolated in the USSR with those of HIV strains previously isolated in Europe, USA, and Africa.

The paper deals with further search for substances modifying metabolic processes, changing the conditions of virus existence in the host cell and, consequently, possessing a certain antiviral activity. The antiviral effects of aromatic carbonic acids amides including trisubstituted benzamides and nicotinamide were tested. Five out of 8 substances tested possessed antiviral activity which might be due to their capacity to inhibit the activity of the enzymes of ADP-ribosylation. By blocking cellular processes of ADP-ribosylation, the substances under study depressed DNA capacity for reparation, inhibited differentiation and transformation of cells, i.e. had an indirect effect on reproduction of viruses. The universal nature of the processes coursing with participation of NAD(+)-dependent ADP-ribosylation suggests that the range of antiviral activity of inhibitors of mono- and poly-ADP-ribosylation would not be limited to HIV infection but would be rather wide.