[Herpesvirus type 8 and its implication in human pathology].

Herpesvirus type 8 or Kaposi's sarcoma-associated virus has been recently discovered and it is an etiologic agent of several known diseases. It has common features that link it with other representatives of the family Herpesviridae: similar structural elements and genomic organization, and the common mechanisms of replication. Nevertheless, this virus has a number of unique features that make it an interesting matter for investigations and currently central in modern medicine and biology. This overview is to draw attention to this representative of herpesviruses and to outline some epidemiological, pathogenetic, and molecular aspects of this problem.

[Combined use of killed vaccines and immunomodulator ridostin for urgent prevention of epidemic stomatitis, Aujeszky disease and carnivore plague in experiment]. / Sochetannoe ispol'zovanie ubitykh vaktsin i immunomoduliatora ridostina dlia ékstrennoi profilaktiki iashchura, bolezni Aueski i chumy plotoiadnykh v éksperimente.

Results of experimental studies of mice and pigs infected with foot-and-mouth disease virus, minks infected with Aujeszky's disease virus, and dogs infected with canine distemper virus are described. In animals with foot-and-mouth disease and Aujeszky's disease, combined treatment with killed vaccine and immunomodulator Ridostin by the scheme of urgent prophylaxis (3 days before infection) caused 75% (foot-and-mouth disease) and 100% (Aujeszky's disease) prevention of animal death and development of generalized infection. The use of Ridostin by the scheme of urgent prophylaxis in a canine distemper infection focus arrested clinical symptoms of the disease in 50% of animals received immunomodulator. Clinical symptoms of canine distemper in the other dogs treated with immunomodulator were manifested in a mild form, and their appearance was delayed to 23-25 days after contact with infected animal.

[Development of a suppository form of the interferon inducer poludan and potentiation of its action by hyaluronic acid]. / Razrobotka svechevoi formy induktora interferona poludan i potentsirovanie ego deistviia gialuronovoi kislotoi.

A promising dosage form of interferon inductor poludan has been developed for the treatment of patients with genital herpes and ophthalmic herpes: suppositoria. High interferon-producing and antiviral activity of poludan in suppositoria is potentiated by hyaluronic acid and antioxidants.

[The antitumor action of double-stranded interferon inducers (larifan, ridostin) and reaferon in an experiment]. / Protivoopukholevoe deistvie dvuspiral'nykh induktorov interferona (larifana, ridostina) i reaferona v éksperimente.

Interferon inducers larifan and rhidostin, and reaferon were shown to exert an inhibiting antitumor effect manifested in the prolongation of the incubation period, decrease of the size of tumors, and longer survival of the animals. The maximal anti-tumor and immunomodulating effect was obtained by combined use of preimmunization with tumor cells and simultaneous administration of reaferon or interferon inducers, larifan and rhidostin. Larifan was also shown to have a greater antitumor activity than rhidostin. Larifan, however, was maximally active only in combination combination with vaccination using syngeneic cells of the virus-induced tumor. In this case levels of alpha and gamma interferons were 2-4 times higher than normally.

[Anti-idiotypic antibodies against antibodies to the herpes simplex virus and its early antigens]. / Antiidiotipicheskie antitela protiv antitel k virusu prostogo gerpesa i ego rannim antigenam.

Polyclonal anti-idiotypic antibodies (anti-Id-AT or AT2) were produced to AT idiotopes of virion antigens--structural proteins of herpes simplex virus (HSV) and of early virus-induced antigens (VIA). The method of SPRIA established that anti-Id-AT seemed to be associated with AT active centers. Besides, immunization with anti-Id-AT produced anti-anti-Id-AT (AT3) similar in their specificity with antiviral AT or anti-VIA. It was shown that AT2 could be used as a diagnostic preparation instead of specific antigen for the detection of antibody to HSV or VIA in human sera by indirect RIA.

[Immunity to tumors induced by herpes simplex virus in hamsters]. / Immunitet k opukholiam, indutsirovannym virusom prostogo gerpesa u khomiakov.

Preparations of early herpes simplex virus antigen (VIA) and specific antibodies to it were used to induce active and passive immunity to herpes virus-induced tumors in experimental animals. The results demonstrated the increased resistance of animals to transplantation of tumor cells due to vaccination with VIA-containing preparations. Thus, in VIA-vaccinated animals there was a delay in the development of tumors and the survival time was significantly higher than in the controls. The sera of these animals contained antibodies to VIA in high titres. Experiments with passive immunization also gave encouraging results.

[Early antigens induced by cytomegalovirus in human tumor and leukemia cells]. / Rannie antigeny, indutsirovannye tsitomegalovirusom, v opukholevykh i leikoznykh kletkakh cheloveka.

Immunological methods (complement fixation test, immunofluorescence) demonstrated that the antigen associated with cytomegalovirus can be detected in some malignant and benign tumors and lymphoid cells in human leukemia. No antigen of the same specificity was found in tissues from the same patients and in normal donor lymphocytes.

[Determination of the early antigens induced by herpes simplex virus in human tumors by a radioimmunological binding method]. / Opredelenie rannikh antigenov, indutsirovannykh virusom prostogo gerpesa, v opukholiakh cheloveka metodom radioimmunologicheskogo sviazyvaniia.

It is very difficult to produce specific antibody to individual antigens comprising the multicomponent antigenic system of a cell. It is particularly true of the antigens present in the cell in small amounts and characterized by low immunogenic potency, among them early antigens of herpes simplex virus (HSV). To overcome these difficulties the authors propose a method of preparation of a specific serum using specific immune complexes as immunogens. The use of the radioimmune binding method and a new specific serum to early HSV antigen has proved that HSV could be associated not only with cervical carcinoma, as believed by many research workers, but also with tumors of other localization, in particular, lung carcinoma and malignant melanomas.

[Herpes simplex virus-associated antigen in leukemic cells]. / Antigen, assotsiirovannyi s virusom prostogo gerpesa v leikoznykh kletkakh.

Immunological methods (CFT, indirect IF) detected herpes simplex virus-associated antigen in leukocytes of 21 out of 56 leukemia patients. The antigen was more frequently found in leukocytes of patients with chronic lympho- and myeloleukemias, less frequently in acute forms of these diseases. No antigen was detectable in leukocytes of normal donors.

[Virus-induced antigens in human tumors]. / Virusindutsirovannye antigeny v opukholiakh cheloveka.

Solid-phase radioimmunoassay (SPRIA) was used for examinations of human malignant tumors for the presence of retrovirus D-induced antigen and of blood sera from cancer patients for the presence of antibody to this antigen. Various tumor specimens differently reacted to anti-HEp-2 serum, the background values of binding of this serum with normal tissues (liver, lung, spleen) and leukemic cells from leukemia patients being low. The majority of the sera from cancer patients were found to contain antibody to HEp-2 antigen. No correlation was established between high levels of the antigen in tumors and high antibody titres in the blood sera of the same patients.

[Association of retrovirus D with human malignant neoplasms]. / Assotsiatsiia retrovirusa D so zlokachestvennymi novoobrazovaniiami cheloveka.

Immunological methods of investigation (CFT, immunofluorescence and radioimmunoassay) showed that the antigen induced by retrovirus D was discovered in some malignant and benign human tumors of various localizations. No association of retrovirus D with human hemoblastoses could be established.

[Antigens associated with herpes simplex viruses in human and animal tumors]. / Antigeny, assotsiirovannye s virusami prostogo gerpesa v opukholiakh cheloveka i zhivotnykh.

The paper deals with the mechanism of emergence of early virus-induced antigens in animal tumors and their association with carcinogenesis. Problems of the specificity of the antigens of tumors induced by herpes simplex virus in different animal species and their immunogenicity for the tumor carriers are discussed.

[DNA from retrovirus D-infected cells and from human tumors: an inducer of the synthesis of a new nonvirion antigen]. / DNK iz infitsirovannykh retrovirusom D kletok i iz opukholei cheloveka--induktor sinteza novogo nevirionnogo antigena.

The role of intracellular DNA from HEp-2 cell culture chronically infected with retrovirus D in generation of new non-virion antigen associated with this virus was studied. In transfection experiments, 23 DNA samples obtained from cells of variously localized human tumors were studied for the capacity to induce a new antigen of the same specificity. The DNA obtained from HEp-2 cells was found to be capable of inducing the new antigen production in a number of cells systems. The original cells contained no such antigen before inoculation. DNAs from 14 cancer tumors of the mammary glands, lungs, and gastrointestinal tract induced the synthesis of the new antigen in vitro and other cells indicating the presence of these tumor cells of at least a portion of viral genome responsible for the synthesis of the new retrovirus D-associated antigen. No production of this antigen was induced by any of the 6 specimens of normal tissues.

[New antigen induced by herpes simplex virus in human tumors]. / Novyi antigen, indutsirovannyi virusom prostogo gerpesa, v opukholiakh cheloveka.

The study showed the new antigen induced by herpes simplex virus type 2 (HSV-2) to be present not only in cancer tumors of the cervix and corpus uteri, and ovaries but also in malignant tumors of the mammary glands, kidneys, urinary bladder, as well as in tissues of fibrous-cystic mastopathy and fibroadenoma of the mammary glands. In malignant tumors of the cervix, however, the HSV-2-induced antigen was found more frequently and had a higher serological activity than in other tumors. In contrast to tumors, this antigen was not detected in normal tissues. Among 25 specimens of malignant cervical tumors containing the virus-induced antigen, 8 specimens contained virus antigen and 4 yielded biologically active virus. The virus-induced antigen is found in the tumors much more frequently then viral antigen or virus. Detection in the tumors of this new antigen demonstrates the presence in them of viral genetic information coding for the synthesis of this antigen as confirmed by transfection experiments.

[Retrovirus D-induced antigen in human tumors]. / Antigen, indutsirovannyi retrovirusom D, v opukholiakh cheloveka.

Tissues of malignant and benign tumors from 254 patients were examined for the presence in them of a new, retrovirus D-associated antigen. Most frequently, the virus-induced antigen was present in pulmonary carcinomas (54.5%) and in large intestine tumors (25%). This antigen was detected almost with the same frequency (11%-12.5%) in fibroadenomas and mammary carcinomas, only in 8% of gastric tumors and very rarely in fibrous-cystic mastopathies (2.6%). No virus-induced antigen was found in tissues not involved in the cancer process or in tissues of normal subjects. Detection of the retrovirus D-associated antigen in tumor cells indicates the presence in them of this virus or its genome.

[New antigens induced by herpes simplex virus in human tumors]. / Novye antigeny, indutsirovannye virusom prostogo gerpesa, v opukholiakh cheloveka.

Tissues of malignant tumors of the genitalia (cervix, uterus body, ovary) contain a specific antigen associated with herpes simplex virus type 2 (HSV-2) identical with the antigen of the infected cells. The virus-induced antigen was detected in tissues of cervical carcinoma in 35% of cases, in 15% of tumors of the corpus uteri and in 13% of ovary tumors. HSV-2 was isolated from pathologically altered cervical carcinoma cells in 2 out of 56 cases examined. These facts indicate the presence of HSV-2 genetic information in cells of some tumors. No virus-induced antigen was found in any of the 7 specimens of normal nontumorous tissue examined.

[DNA from cells infected with herpes simplex virus and from human tumors as an inducer of synthesis of a new nonvirion antigen]. / DNK iz infitsirovannykh virusom prostogo gerpesa kletok i opukholei cheloveka kak induktor sinteza novogo nervirionnogo antigena.

DNA from herpes simplex virus type II (HSV-II)-infected cells isolated by using SDS, phenol, and pronase as well as by a new method of Pignatti et al. from triton X-100-NaCl-supernatant was shown to be capable to induce production of an early nonvirion (new) antigen in sensitive systems of Vero, RS-537 cells and others. It was also established that as a result of transfection of DNA recovered from 13 speciment of cancer tumors of the cervix and ovaries (9 tumors contained the new antigen and 4 were free from it), the new antigen associated with HSV-II was synthesized in 8 cases in the sensitive cells as early as 6 hours postinoculation whereas no viral antigens could be detected by this time. No viral antigens could be detected within 24 hours either, with the exception of 3 cases where CPE also developed by 24 hours indicating the appearance of the virus. DNA recovered from normal tissues of the cervix was incapable of inducing the new antigen.

[Detection of new antigens, induced by retrovirus D, by a quantitative complement fixation micromethod using radioactive chromium]. / Vyiavlenie novykh antigenov, indutsiruemykh retrovirusom D, kolichestvennym mikrometodov fiksatsii komplementa s ispol'zovaniem radioaktivnogo khroma.

The additional evidence of the existence of antigenic differences between the early virus-induced antigen and structural retrovirus D antigens as well as antigens from human fetus normal tissues was obtained by quantitative complement fixation micromethod using radioactive chromium (51Cr-CFT). In examinations of 13 specimens of cancer tumours and fibroadenomas of the female mammary glands the new antigen was found in 8 cases, including 4 cancer tumours where this antigen could not be detected by the conventional CFT.

[Virus-induced antigen in cells infected with the herpes simplex virus]. / Virusindutsirovannyi antigen v kletkakh, infitsirovannykh virusom obychnogo gerpesa.

A new antigen differing from those of mature virion and noninfected cell was shown to appear in herpes simplex (HSV) virus-infected cells. It is virus-specified since the nonvirion antigen had a similar determinant in cells of different species origin. Nonvirion antigens induced by HSV types 1 and 2 were serologically similar. Differences in the specific activity of sera to the new nonvirion antigen and mature virus antigens were established by three different methods: complement fixation test, mixed hemadsorption, and biological neutralization. The early virus-induced antigen found in HSV-infected cells differed by many properties from the antigen previously described by Tarro and Sabin (1970).