RESUMEN
The investigation was undertaken to study the molecular characteristics of Epstein-Barr virus (EBV) LMP1 gene samples amplified from the tumor and intact tissues of patients with EBV-negative forms of gastric carcinoma (GC). The genetic structure of these samples determined by their sequencing was compared with that of the gene samples isolated from the cells of oropharyngeal washing specimens from the same patients with GC, as well as peripheral blood lymphocytes of patients with infectious mononucleosis (IM) and blood donors. The findings suggest that the samples of tumor tissue LMP1 from patients with GC have higher divergence than those from patients with IM and blood donors although no specific variants of the gene for GC were found. Comparison of LMP1 sequences from tumor tissue and cells of oropharyngeal washing specimens from the same patients with EBV-negative GC revealed the common LMP1 variant in 2 cases while they differed in 3 cases. The findings are an initial step in studying the role of EBV in the carcinogenesis of EBV-negative GC that is likely to be established by investigations on representative clinical material, by applying the up-to-date technologies.
Asunto(s)
Carcinoma/virología , Herpesvirus Humano 4/genética , Neoplasias Gástricas/virología , Proteínas de la Matriz Viral/genética , Adulto , Anciano , Carcinoma/química , Femenino , Técnica del Anticuerpo Fluorescente , Genes Virales/genética , Herpesvirus Humano 4/química , Humanos , Masculino , Persona de Mediana Edad , Faringe/virología , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Estómago/virología , Neoplasias Gástricas/química , Proteínas de la Matriz Viral/metabolismoRESUMEN
Epstein-Barr virus (EBV) is an etiological agent of a number of benign and malignant human diseases, such as infectious mononucleosis (IM), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). EBV latent membrane protein 1 (LMP1) gene (recognized as a viral oncoprotein) of various clinical and geographical origin was found to have different types of amino acid mutations affecting its biological activity. Since there was no information on the strain differences in LMP1 of EBV persisting in Russia, the authors made a sequence analysis of LMP1 samples amplified from the biological materials of Russian patients with IM, HL, and NHL and healthy individuals. The studies have shown that LMP1 variants of Russian origin are a mixed heterogeneous group containing both the earlier characterized and presumably new genetic variants. Among the point amino avid substitutions, the mutations S366T, F106Y, 185L, and E328Q associated with the enhanced transforming activity of a LMP1 molecule and its reduced cytotoxicity. There was no specific association between the certain Russian variants of LMP1 and the specific forms of the disease (IM, HL, and NHL).
Asunto(s)
Infecciones por Virus de Epstein-Barr/virología , Genes Virales , Herpesvirus Humano 4/genética , Proteínas de la Matriz Viral/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Portador Sano/virología , Variación Genética , Herpesvirus Humano 4/química , Herpesvirus Humano 4/patogenicidad , Enfermedad de Hodgkin/virología , Humanos , Mononucleosis Infecciosa/virología , Linfoma no Hodgkin/virología , Datos de Secuencia Molecular , Proteínas Oncogénicas Virales/genética , Mutación Puntual , Reacción en Cadena de la Polimerasa , Federación de Rusia , Alineación de Secuencia , VirulenciaRESUMEN
The samples of tumor biopsy, blood, and saliva from 10 patients with Hodgkin's disease, 10 patients with non-Hodgkin's lymphoma, and the blood samples of 20 donors were tested by polymerase chain reaction (PCR) for standard (wild) B95-8 and Cao-like (deleted) variants of the LMP1 gene. The paraffin sections of most PCR-tested tumors were also investigated by immunohistochemistry using the monoclonal antibodies S12 or 7D7 to detect the expression of the standard or Cao-like variants of LMP1 protein, respectively. It is suggested that Eptein-Barr virus (EBV) that contains the above deletion is not crucial for the development of the study lymphoproliferative malignancies. The fact that in some cases there is the Cao-like variant of LMP1 in the tumor biopsy specimen and its standard variant LMP1-B95-8 in the biological fluids of the same patient is very likely to suggest that the patient is infected with both types of the virus or there is genetic mutation(s) of EBV during viral carcinogenesis preceding or accompanying the development of a tumor.
Asunto(s)
Genes Virales , Herpesvirus Humano 4/genética , Enfermedad de Hodgkin/metabolismo , Linfoma no Hodgkin/metabolismo , Proteínas de la Matriz Viral/genética , Biopsia , Células Sanguíneas/metabolismo , Eliminación de Gen , Variación Genética , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/virología , Humanos , Inmunohistoquímica , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/virología , Reacción en Cadena de la Polimerasa , Saliva/metabolismo , Especificidad de la Especie , Proteínas de la Matriz Viral/biosíntesisRESUMEN
The paper presents the results of the studies of gastric cancer (GC) associated with Epstein-Barr virus (EBV) among the patients residing in 4 geographical regions. In situ hybridization (ISH) techniques revealed that 49(11.4%) of the 430 examinees were EBV positive (EBV+), the virus-specific marker mRNA-1 of EBV, EBER-1) was found to be present in 80-100) of tumor cells. The proportion of EBV(+)-associated GC cases in different geographic regions ranged from 7.3 to 15%. These tumors were predominant in males (15%) as opposite to females (5.5%). Histological types most common among EBV+ tumors and their location in the stomach are also described. Serological findings indicated that the increased anti-EDV antibody response in 70% of GC cases coincided with the presence of the viral genetic information detected by ISH. In contrast to a humoral response to EBV, a humoral response to Helicobacter pylori was equal both in patients with EBV(+)- and EBV(-)-associated gastric tumors. Further molecular biological analysis of EBV isolates from virus positive and virus negative GC may answer the question whether there are really the so-called tumor and non-tumor variants of EBV.
Asunto(s)
Adenocarcinoma/complicaciones , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/inmunología , Neoplasias Gástricas/complicaciones , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adenocarcinoma Mucinoso/epidemiología , Adenocarcinoma Mucinoso/etiología , Adenocarcinoma Mucinoso/patología , Adulto , Anticuerpos Antivirales/análisis , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/inmunología , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/inmunología , Herpesvirus Humano 4/genética , Humanos , Hibridación in Situ , Masculino , Persona de Mediana Edad , Moscú/epidemiología , ARN Mensajero/análisis , ARN Viral/análisis , Federación de Rusia/epidemiología , Factores Sexuales , Siberia/epidemiología , Estómago/patología , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/patologíaRESUMEN
Phylogenetic analysis of HTLV-I variants persisting among population of Turkmenistan and the Republic of Georgia (situated on both sides of the Caspian Sea, not far from a known HTLV-I cluster in Northern Iran) has been carried out. HTLV-I isolates from the above countries were obtained in the course of seroepidemiological investigations. In all, 1,510 blood-donor samples from Turkmenistan and 47 blood samples from hematological patients from Georgia, were tested with different screening and confirmatory assays, including commercial ones. As a result, 7 infected individuals (3 blood donors and 4 relatives of one blood donor) from Turkmenistan and 3 infected individuals (one ATL patient and 2 of his relatives) from Georgia were found. In addition, 4 HTLV-I isolates from Turkmenistan and one from Georgia were cloned and part of their LTR was sequenced. Phylogenetic analysis of sequenced isolates allowed us to conclude that these isolates belonged to sub-type A, one of 3 sub-types of the "Cosmopolitan" type. We found that most of the Turkmenian isolates formed a tight cluster and shared common nucleotide substitutions with isolates originating from Northern Iran (Mashhad). The data obtained suggest that there is a new endemic focus of HTLV-I infection in the Caspian Sea region. Further investigations are required to confirm this hypothesis.
Asunto(s)
Infecciones por HTLV-I/epidemiología , Virus Linfotrópico T Tipo 1 Humano , Adolescente , Adulto , Donantes de Sangre , Femenino , Georgia (República)/epidemiología , Virus Linfotrópico T Tipo 1 Humano/clasificación , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Masculino , Persona de Mediana Edad , Linaje , Filogenia , Turkmenistán/epidemiologíaRESUMEN
Seroepidemiological and molecular-biological screening of 1510 donor blood samples, collected from the residents of the town of Ashgabat (Turkmenistan), for lymphotropic virus of human T-cellular leukemia (HTLV) virus revealed one donor with a high level of immune response to a wide spectrum of viral proteins. Three donors were serologically assessed as dubious, for their sera contained antibodies to gag gene protein but no antibodies to env gene protein. Screening of family members of the donor infected with HTLV-1 revealed four more highly reactive carriers of HTLV-1 virus. The presence of proviral sequences of HTLV-1 in the lymphocyte DNA of infected donor and her relatives was confirmed by polymerase chain reaction and subsequent Southern-blot hybridization of specific amplification products. Proviral sequences of gag, pol, and LTR genes were detected in all the cases. Short-term culturing of peripheral blood lymphocytes of all seropositive subjects was associated with expression of HTLV-1 structural proteins. Analysis of the possible routes of transmission of HTLV-1 isolated in Turkmenistan permits us to hypothesize an Iranian origin of the isolated virus strain.
Asunto(s)
Infecciones por HTLV-I/epidemiología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Adolescente , Adulto , Anciano , Southern Blotting , ADN Viral/análisis , Femenino , Infecciones por HTLV-I/genética , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Masculino , Persona de Mediana Edad , Linaje , Reacción en Cadena de la Polimerasa , Turkmenistán/epidemiologíaAsunto(s)
Anticuerpos Anti-HTLV-I/sangre , Infecciones por HTLV-I/etnología , Anticuerpos Anti-HTLV-II/sangre , Infecciones por HTLV-II/etnología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Infecciones por HTLV-I/inmunología , Humanos , Masculino , Persona de Mediana Edad , Siberia/epidemiologíaAsunto(s)
Infecciones por HTLV-I/epidemiología , Virus Linfotrópico T Tipo 1 Humano/genética , Filogenia , Adulto , Anciano , Secuencia de Bases , ADN Viral , Femenino , Genes Virales , Genes gag/inmunología , Humanos , Inmunoensayo , Japón/epidemiología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Nativos de Hawái y Otras Islas del Pacífico , Reacción en Cadena de la Polimerasa , Grupos Raciales , Federación de Rusia/epidemiología , MigrantesAsunto(s)
Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/inmunología , Secuencias Repetitivas de Ácidos Nucleicos , Proteínas Virales/inmunología , Diferenciación Celular , Herpesvirus Humano 4/metabolismo , Humanos , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/virología , Proteínas Virales/genéticaAsunto(s)
Infecciones por Deltaretrovirus/epidemiología , Adulto , Anciano , Pueblo Asiatico , Etnicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Federación de RusiaRESUMEN
An HTLV-I-associated case of adult T-cell leukemia (ATL) was described in a 51-year-old white man, native from Georgia, the former U.S.S.R. Clinical manifestation of the disease (enlarged lymph nodes, bone marrow and peripheral blood changes, CNS-involvement, cutaneous lesions and hypercalcemia) as well as laboratory findings were recognized to be very similar to those frequently observed in ATL patients from endemic regions. Mature T-helper surface phenotype detected on peripheral blood lymphocytes of the patient (OKT3-, OKT4+ and OKT8-) and aggressive course of the disease were also in favour of classical type ATL developed in the patient. The HTLV-I antibody presence in an ATL patient was repeatedly confirmed by serological tests (Abbott HTLV-I EIA and Serodia HTLV-I), immunofluorescence and Western blot assay. The latter revealed the presence of a large spectrum of HTLV-I-specific antibodies (to p19, p24, p26, p28, p32, p36, pr53, gp21, gp46, gp62 and gp68 of HTLV-1). The HTLV-I-specific antibodies have also been detected in serum samples of the patient's wife and son. The presence of HTLV-I provirus in the primary ATL patient's PBL was clearly demonstrated by PCR and Southern blot analysis. This case, with the HTLV-I infections detected in two other family members, suggests that in Europe, HTLV-I-positive cases of ATL can occur in virus-infected local people with much wider distribution than that hitherto supposed.
Asunto(s)
Seropositividad para VIH/complicaciones , Virus Linfotrópico T Tipo 1 Humano , Leucemia de Células T/microbiología , Leucemia de Células T/patología , Anticuerpos Antivirales/análisis , Antígenos CD/análisis , Western Blotting , Productos del Gen env/genética , Productos del Gen env/inmunología , Genes Virales/genética , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 1 Humano/inmunología , Humanos , Leucemia de Células T/sangre , Masculino , Persona de Mediana Edad , Fenotipo , Reacción en Cadena de la Polimerasa , Provirus/genética , Proteínas Oncogénicas de Retroviridae/genética , Proteínas Oncogénicas de Retroviridae/inmunologíaRESUMEN
This is the first presentation of information on the circulation of human herpes virus type 6 (HHV-6) in the population of the mid-European part of this country. The results of the study indicate that HHV-6 is widely spread both among apparently normal people and among patients with different pathologies. The studies using immunofluorescence test showed that the percentage of HHV-6-infected subjects was practically similar among blood donors, patients with nasopharyngeal cancer, rheumatoid arthritis, hemophilia, and patients with transplanted kidney, varying from 34% to 49%. A significantly higher per cent (66%) and higher antibody titres to HHV-6 were detected in sera from patients with hemoblastoses. A high level of HHV-6 infection among patients with hemoblastoses was also confirmed by the results of immunoblotting showing a wider spectrum and higher intensity of the detectable proteins. It should be noted that the amounts of virus-specific proteins detectable by some sera showed individual variations indicating different levels of expression of viral proteins in different individuals.
Asunto(s)
Herpesvirus Humano 6/aislamiento & purificación , Anticuerpos Antivirales/sangre , Especificidad de Anticuerpos , Artritis Reumatoide/inmunología , Donantes de Sangre/estadística & datos numéricos , Hemofilia A/inmunología , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/microbiología , Herpesvirus Humano 6/inmunología , Humanos , Trasplante de Riñón/inmunología , Leucemia/inmunología , Neoplasias Nasofaríngeas/inmunología , Prevalencia , Federación de Rusia/epidemiología , Estudios SeroepidemiológicosAsunto(s)
Donantes de Sangre , Anticuerpos Anti-HTLV-I/sangre , Electroforesis en Gel de Poliacrilamida , Reacciones Falso Negativas , Reacciones Falso Positivas , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-I/etnología , Humanos , Immunoblotting , Kazajstán/epidemiología , Kirguistán/epidemiología , Estudios Seroepidemiológicos , Tayikistán/epidemiología , Uzbekistán/epidemiologíaAsunto(s)
Infecciones por HTLV-I/epidemiología , Leucemia/epidemiología , Linfoma no Hodgkin/epidemiología , Anticuerpos Anti-HTLV-I/sangre , Infecciones por HTLV-I/diagnóstico , Humanos , Immunoblotting , Leucemia/diagnóstico , Linfoma no Hodgkin/diagnóstico , Juego de Reactivos para Diagnóstico , Estudios Seroepidemiológicos , Pruebas Serológicas , U.R.S.S./epidemiologíaRESUMEN
The first of case of adult T-cell prolymphocytic lymphosarcoma is reported which according to the natural course, cell composition of tumor, cell surface markers as well as expressed immune response to a wide spectrum of HTLV-1 gag an env encoded proteins can be classified as HTLV-associated adult T-cell leukemia. Diagnosis of the tumor alongside with identification of HTLV-1-infected individuals in the USSR emphasizes the need to stimulate research in HTLV-1-associated carcinogenesis in this country.
Asunto(s)
Anticuerpos Anti-HTLV-I/análisis , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto/epidemiología , Regulación Viral de la Expresión Génica , Productos del Gen gag/análisis , Anticuerpos Anti-HTLV-I/genética , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 1 Humano/inmunología , Humanos , Immunoblotting , Leucemia-Linfoma de Células T del Adulto/inmunología , Masculino , Persona de Mediana Edad , U.R.S.S./epidemiologíaRESUMEN
The results of serologic survey of 4118 residents of the USSR Far East from 16 to 82 years of age and 1037 blood donors for antibody to HTLV-I by the method of passive agglutination of gelatin particles coated with viral proteins are summarized. The portion of HTLV-1 seropositive subjects in the Khabarovsk Territory was 1.79% (25 out of 1391), in the Maritime Territory 2.2% (18 out of 801), in the Sakhalin Island 1.6% (26 out of 1557), and in Kamchatka 1.6% (6 out of 369). A discrete area of a higher number of positive cases was found among Nivkhi national group in the village of Nogliki in the Sakhalin Island: 6.4% (10 out of 155). In women, antibody to HTLV-1 was found twice as frequently as in men. Seropositives to HTLV-1 among blood donors in Moscow, the town of Komsomol'sk-na-Amure, and the town of Yuzhno-Sakhalinsk comprised 1.4%, 1.6%, and 5.45%, respectively. The occurrence of HTLV-1 infection among the normal population of the Far East and especially among blood donors attests to the expedience of wider seroepidemiological surveys of the population and especially donors for HTLV-I infection in other regions of the USSR as well.
Asunto(s)
Anticuerpos Anti-HTLV-I/sangre , Infecciones por HTLV-I/prevención & control , Tamizaje Masivo , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Pruebas de Aglutinación , Especificidad de Anticuerpos , Donantes de Sangre , Femenino , Infecciones por HTLV-I/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Factores Sexuales , Siberia/epidemiología , Siberia/etnologíaRESUMEN
As many as 97 patients with myocardial lesions: congestive and hypertrophic cardiomyopathy (CMP), postmyocarditis CMP (PM CMP), myocarditis (MC), alcoholic heart injury (AHI), coronary heart disease (CHD), vegetodysovarian myocardiodystrophy were examined by means of a complex of the virological tests (for Coxsackie B, Epstein-Barr and hepatitis B viruses) and immunoassays (for antibodies to different components of the myocardium, leukocyte migration inhibition test, antibody-dependent cellular cytotoxicity test, measurements of T and B lymphocytes and their subpopulations, and so forth). Virus infection was shown to be of a role for the onset of acute MC (usually reversible) and congestive CMP. At the same time the autoimmune mechanisms of the lesions were conclusively ascertained in MC associated with heart failure and in PM CMP. In patients with congestive CMP and AHI coupled with heart failure, antibodies to nerve fibers of the myocardium could be demonstrated in the presence of T-lymphocyte deficiency and high titers of antibodies to Epstein-Barr virus. This does not allow excluding myocardial denervation leading to refractory heart failure. Some immunological parameters made use of in the study provide an opportunity of an objective evaluation of the effect glucocorticoid treatment produces on patients suffering from MC and PM CMP.
Asunto(s)
Cardiomiopatías/diagnóstico , Miocarditis/diagnóstico , Virosis/diagnóstico , Anticuerpos Antivirales/sangre , Formación de Anticuerpos , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/inmunología , Cardiomiopatías/etiología , Cardiomiopatías/inmunología , Cardiomiopatía Alcohólica/diagnóstico , Cardiomiopatía Alcohólica/etiología , Cardiomiopatía Alcohólica/inmunología , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/etiología , Cardiomiopatía Dilatada/inmunología , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/etiología , Cardiomiopatía Hipertrófica/inmunología , Femenino , Humanos , Inmunidad Celular , Masculino , Miocarditis/etiología , Miocarditis/inmunología , Virosis/complicaciones , Virosis/inmunologíaRESUMEN
Sera from 867 donors were tested for antibodies to the virus of T-lymphocyte leukemia of adults (HTLV-I) in parallel by indirect immunofluorescence on acetone-fixed cells of HUT-102 culture producing HTLV-I and by agglutination test using a commercial set ("Serodia-ATLA", Japan). Twelve (1.38%) out of 867 sera were positive in the agglutination test and only 7 of them in immunofluorescence test. The specificity of the results was verified by absorption experiments. The activity of the sera in the agglutination test disappeared completely after their absorption with HUT-102 culture cells but did not change after absorption with LLU cells producing no HTLV-I despite a low percent of virus infection, donor blood control for HTLV-I infection becomes mandatory.
Asunto(s)
Donantes de Sangre , Anticuerpos Anti-HTLV-I/análisis , Adulto , Pruebas de Aglutinación , Especificidad de Anticuerpos , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Masculino , Persona de Mediana Edad , Moscú , Población UrbanaRESUMEN
Antibodies to Epstein-Barr virus have been detected in sera from 1538 healthy adult persons living in the south of Siberia and Far East. It has been shown that the virus infectivity varied from 77% in Russians of the Yakutsk ASSR to 100% in Orochi and Russians residing in the territory of the Gorno-Altai Autonomous Province. Antibody levels to the Epstein-Barr virus for inhabitants of the south regions were higher than those for inhabitants of the north regions.