[The blocking effects of small interfering RNAs on RS-1 gene functions of herpes simplex virus type 2: new perspectives for targeted antiviral exposure].

A new target has been revealed for therapy for herpes simplex type 2. The target is RS1 mRNA whose activation is a key stage in regulating the expression of the early genes of herpes simplex virus type 2 (HSV-2). The targeted knockdown of the function of this gene by small interfering RNAs (siRNAs) has been found to result in the complete suppression of HSV-2 infection. The designed interfering RNAs are able to interact with both HSV-1 and HSV-2. The findings suggest that siRNAs have protective properties against the cytopathic effect of HSV-2 and cause no toxicity to infected Vero cells.

[Comparative estimation of the indicators of interferon, immune, and cytokine states in the comprehensive study of patients with herpesvirus infections].

The paper provides the data of a comparative analysis of the indicators of immune and interferon states and cytokine profile and the results of virological studies in patients with different (acute and chronic) forms of mixed herpesvirus infection (with virus simplex herpes types 1 and 2, Epstein-Barr virus, human herpesvirus type 6, and others). Pronounced changes were found in immune responses in such patients. There were decreases in IFN-alpha and IFN-gamma values in 36 and 13%, respectively; 51% of the subjects showed a reduction in both IFN-alpha and IFN-gamma along with the high titers of antibodies to viruses of the Herpesviridae family and their infectious activity. There were changes in the cytokine profile, activation of IFN-alpha, IL-2, IL-8, IL-10, and IL-18 gene expression, and suppression of IL-2 gene transcription in the majority of the patients. Determination of IFN susceptibility revealed that 86% of the subjects responded to IFN-alpha therapy and only 11% of cases did to IFN-gamma one.

[Inhibitory effect of foscarnet and acyclovir on reproduction of human herpesvirus 6 in cell culture].

Two practically important antiviral agents, i.e. foscarnet (phosphonoformic acid, foscavir) and acyclovir, and their inhibitory effect on reproduction of human herpesvirus 6 (HHV-6) were investigated in an experiment with sensitive lymphoblastoic cell line HSB-2. Phosphonoformic acid (PFA) was shown advantageous vs. acyclovir. In a model of HHV-6 infection acyclovir was low active (chemotherapeutic index of 0.9) and its use in clinical practice is not useful, whereas PFA (chemoterapeutic index of 10) and similar agents showed significant antiviral activity that indicated the necessity of their further investigation.

[Etiotropic medicinal therapy of viral infections]. / Etiotropnaia lekarstvennaia terapiia virusnykh infektsii.

The paper contains a description of modern data on etiotropic therapy (chemotherapy) for widespread and socially-significant viral infections, like influenza, acute respiratory lesions, herpes-virus infections, hepatitis, AIDS and other extra dangerous viral infections. The survey focuses on the contribution of Russian researchers to creating antiviral chemopreparations.

[Laboratory diagnosis of human herpes virus infection]. / Laboratornaia diagnostika gerpesvirusnoi infektsii cheloveka.

Reviews modern data on laboratory diagnosis (virological, immunobiochemical, molecular biological methods) and differential diagnosis of herpesvirus infection induced by various Herpesviridae.

[Human type 6, 7, and 8 herpesviruses--new pathogens in the Herpesviridae family]. / Virusy gerpesa cheloveka 6, 7 i 8-go tipov--novye patogeny semeistva Herpesviridae.

Presents modern data on a group of novel viruses pathogenic for man: types 6, 7, and 8 human lymphotropic herpesviruses (HHV-6, HHV-7, and HHV-8). HHV-6 and HHV-8 are characterized by wide cell tropism, and HHV-7 is selectively tropic to CD4+ T-lymphocytes. HHV-6 and HHV-7 are etiological agents of exanthema subitum (roseoia infantum), a disease of infancy, and of many grave lymphoproliferative disorders, and HHV-8 is a herpesvirus associated with Kaposi's sarcoma. The morphology, immunobiology, pathogenesis, clinical picture, epidemiology, and therapy of HHV, HHV-7, and HHV-8 infection are characterized in brief.

[Isolation of acyclovir-resistant strains of herpes simplex virus from clinical material]. / Izoliatsiia iz klinicheskogo materiala shtammov virusa gerpesa prostogo, obladaiushchikh rezistentnost'iu k antsikloviru.

A total of 115 strains of herpes simplex virus were isolated from clinical material collected in patients with genital herpes. The majority (93%) of isolated strains were sensitive to acyclovir: ID50 varied from 0.15 to 0.80 microgram/ml acyclovir. Eleven (7%) strains from 4 patients were resistant to acyclovir: ID50 was 30-125 times higher in comparison with the reference HSV-1 strain L2.

[The development and testing of test systems for the determination of herpes simplex virus and cytomegalovirus antigens by lanthanide immunofluorescence analysis]. / Razrabotka i aprobatsiia test-sistem dlia opredeleniia antigenov virusa prostogo gerpesa i tsitomegalovirusa metodom lantanidnogo immunofliuorestsentnogo analiza.

On the basis of the lanthanide immunofluorescent assay (LIFA) test systems for the determination of herpes simplex virus (HSV-LIFA) and cytomegalovirus (CMV-LIFA) antigens have been developed. The test system HSV-LIFA includes the sandwich of monoclonal antibodies (McAb) HSV A.3.3. or B-11 to type 2 HSV, strain BH; the test system CMV-LIFA includes the sandwich of rabbit McAb to CMV, strain AD 169. The approbation of the test systems has revealed that they insure the specific detection of HSV and CMV antigens in clinical specimens (urine, blood, liquor, saliva), the LIFA results well correlating with the data on the isolation of viruses in cell cultures, with the results obtained by other diagnostic methods and with clinical manifestations of diseases. LIFA has been shown to be more sensitive than the enzyme immunoassay.

[Detection of viral-bacterial factors responsible for infertility in couples]. / Vyiavlenie spektra virusno-bakterial'nykh faktorov, indutsiruiushchikh besplodie u supruzheskikh par.

A high prevalence of genital infections was revealed in patients suffering for a long time from sterility. The inflammatory process was found to predominate in tubal sterility. In other forms of sterility with asymptomatic urogenital infections the couples are frequently unaware of the disease and are not properly examined. Genital inflammations not diagnosed for many years augment the endocrine disorders and stimulate the development of autoimmune states. Today, a mixed viral/bacterial urogenital infection is the principal cause of reproductive disorders.

[Antiviral activity of the natural immunostimulant "Vegetan" in murine herpetic meningoencephalitis, guinea pig genital herpes, and canine parvoviral enteritis]. / Antivirusnaia aktivnost' prirodnogo immunostimuliatora "Vegetan" pri gerpeticheskom meningoéntsefalite myshei, genital'nom gerpes morskikh svinok i parvovirusnom énterite sobak.

Antiviral activity of vegetan, a new natural immunostimulator, in herpetic meningoencephalitis of mice, genital herpes of guinea pigs, and parvoviral enteritis of dogs was compared to that of acylguanosine and phosphonoformic acid (PFA). Vegetan incorporated in liposomes or pure was the most active if used for prevention 5 days before intracerebral infection of mice with herpes simplex type 1 virus, whatever the dose of infective agent (10 to 100 LD50). Protective efficacy of vegetan was 57-63%, whereas for ara-A, acylguanosine, and PFA these values were, respectively, 20, 25, and 33%. Use of liposomal vegetan preparation ensured a 80% protective effect. Vegetan had a manifest antiviral effect in guinea pigs with genital herpes and in dogs with parvoviral enteritis.

[Activation of viral reproduction in a mixed infection with human immunodeficiency virus and herpes viruses]. / Aktivatsiia reproduktsii virusov pri smeshannoi infektsii virusom immunodefitsita cheloveka i gerpes-virusami.

Mutual activation of reproduction of type 1 HIV and herpes simplex types 1 and 2 viruses (HSV) was observed in simultaneous infection of continuous T-cellular lymphoblastoid lines (CEM, 119, Hut-78, MT-4, Jurkat-tat) and U-937 monocytic line. Syncytium formation and cytodestructive pattern of reproduction of viruses of both families in these cell lines necessitated the use of enzyme immunoassay (EIA) to detect the antigens of these viruses in order to assess the level of reproduction. The concentration of HIV antigens in EIA increased in mixed infection by 1.4 to 2.1 times in different cultures in comparison with the culture infected with HIV-1 alone, and concentrations of HSV-1 and HSV-2 increased by 1.3-1.8 times in mixed infection, in comparison with reproduction in lymphoblastoid cultures infected with HSV alone. EIA was alone used to examine the production of IgG and IgM antibodies to Epstein-Barr virus, another representative of Herpesviridae family, in the blood sera of patients with immunodeficiency states in whose sera antibodies to proteins produced by gag HIV gene (p15/17, p24, p55) were detected. Increased concentration of IgG antibodies were revealed in 36% of these patients, whereas in healthy donors the sera with elevated concentrations of IgG to Epstein-Barr virus were far less incident (12%). A hypothesis about mutual activation of HIV and herpes viruses is put forward.

[The isolation of the herpes virus from the white crane and a study of its properties]. / Vydelenie virusa gerpesa ot belogo zhuravlia i izuchenie nekotorykh ego svoistv.

Isolation of a virus agent from sick white cranes in National Oka Preserve is described. The results of virological and serological studies on specimens from the sick birds permitted a conclusion that the infection in the cranes could be induced by avian herpes virus.

[Human hybridoma neutralizing antibodies to the herpes simplex virus]. / Chelovecheskie gibridomnye neitralizuiushchie antitela k virusu prostogo gerpesa.

Human hybridoma cells producing monoclonal antibodies to human herpes simplex virus were generated. The antibody produced by the hybrid cells interacted with herpes virus types I and II in enzyme immunoassay and complement fixation test, had neutralizing activity both in vivo and in vitro. These human monoclonal antibodies may be used for immunotherapy of herpes virus infection.

[Severe forms of herpes simplex in newborn infants]. / Tiazhelye formy gerpes-virusnoi infektsii u novorozhdennykh.

Generalized herpetic infection in the newborn runs its course in association with cerebral lesions as well as with injuries to the lungs, heart and liver. The infection diagnosis should take into account the mother's epidemiological anamnesis, the clinical manifestations in the child and the results of the simultaneous use of several methods (fluorescent antibody test, IEA, virological test). Of paramount importance is the simultaneous examination of the mother. Of no less importance is echoencephalography, namely the detection of cysts in white matter of the frontal lobes.

[The effect of symptom-free genital herpes on the course and outcome of pregnancy]. / Vliianie bessimptomnogo genital'nogo gerpesa na techenie i iskhody beremennosti.

The incidence of primary genital herpes among women of the childbearing age in Khabarovsk is 2.6% or from 0 to 10.4 per 1000. Asymptomatic herpes simplex virus (HSV) carrier state in the genital tract was detected in 24.1 +/- 5.2% normal women. The virus-carrier state exerts untoward effects on the course of pregnancy and condition of the fetus. In women infected with HSV, the hazard of abortion is 1.8 times as frequent, premature delivery is 3.2 times as frequent, and children of such mothers have symptoms of intrauterine hypotrophy 4.5 times as frequently as normally.

[A comparison of the results of analyzing the clinical data from gynecological, ophthalmological and dental patients using a set of rapid methods for the diagnosis of herpesvirus infection]. / Sopostavlenie rezul'tatov analiza klinicheskikh materialov ginekologicheskogo, oftal'mologicheskogo i stomatologicheskogo profilei naborom ékspress-metodov diagnostiki gerpesvirusnoi infektsii.

Analysis of biological specimens from gynecological, ophthalmological, and stomatological patients was carried out using current express methods for diagnosis of herpes virus infection developed by the authors: enzyme immunoassay (EIA), time-resolved fluoroimmunoassay (tr-FIA), molecular hybridization and conventional immunofluorescence technique. Monoclonal antibodies (MCA) generated by us with epitope specificity for gpD HSV-2 were used in EIA and tr-FIA. F(ab')2-fragments of MCA used as sorbents and for preparation of conjugates were found to be by 250% more sensitive than intact IgG used for similar purposes. The employment of EIA based on MCA F(ab')2-fragments contributed to detection of 0.2-0.6 ng of virus-specific protein in a specimen. Comparison of the results of analysis of clinical specimens of broad spectrum (mucous secreta from the cervical canal of the uterus and posterior vault of the vagina, saliva, lacrimal fluid) by the above express methods for diagnosis of herpes virus infection revealed a high percentage of positive findings, none of the methods providing 100% diagnosis. The use of a set of methods makes the resultant information more objective. Therefore, in future the data obtained by a number of current express methods for herpes diagnosis should be compared.

Treatment of experimental genital herpes with liposomal interferon.

The therapeutic effect of genetically engineered interferon (reaferon) in the treatment of genital herpes in male guinea pigs was studied. The disease was induced in the animals by application of culture liquid containing herpes simplex virus type 2 (HSV-2) to the scarified skin of the penis. The affected sites were treated once daily, for 7 days, with different reaferon preparations 1-3 days after the symptoms of the disease had appeared. Reaferon preparations were most effective in the treatment of experimentally induced genital herpes when incorporated into liposomes, had a less pronounced therapeutic effect when mixed with 3% deoxymethylcellulose to form a hydrocolloid, and were least effective in aqueous solution. Incorporation of the antiviral agents acyclovir and Biolf-62 into liposomes also showed improved effectiveness, in comparison with the free compounds, in the treatment of genital herpes in guinea pigs.