RESUMO
In Venezuela, the isolation of hantaviruses from rodents and the detection, in 1999, of a clinically confirmed human case of hantavirus infection led to increased interest in these viruses. In an attempt to estimate the problem posed by such viruses in Venezuela, ELISA based on purified, recombinant, nucleoprotein were used to check 1380 human serum samples for the presence of IgG antibodies to hantavirus. The ELISA results, as confirmed by indirect immunofluorescence and Western-blot assays, indicated that 23 (1.7%) of the serum samples contained antibodies to hantaviruses. Seroprevalences were similar among all age-groups and for both genders and were no higher among rural populations with a relatively high risk of exposure to rodents than among the overall study population. Although the numbers of samples involved were small, the seroprevalence among the subjects who were residents of Carabobo state was much higher than the overall value (10.3% v. 1.7%; P < 0.01). Human infection with hantavirus appears uncommon but widely distributed in Venezuela.
Assuntos
Anticorpos Antivirais/análise , Infecções por Hantavirus/imunologia , Imunoglobulina G/análise , Orthohantavírus/imunologia , Adolescente , Adulto , Western Blotting/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Imunofluorescência/métodos , Orthohantavírus/isolamento & purificação , Infecções por Hantavirus/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Venezuela/epidemiologiaRESUMO
The rat oncogene neu, and its human homologue HER2, can both cause cell transformation in vitro and tumour formation in vivo, albeit by different mechanisms. 3T3 cells (B104.1.1) transfected with mutated neu (neu) grow as solid tumours in Swiss mice. The purpose of this study was to determine whether immunization with extracts of different 3T3 lines expressing these oncoproteins would lead to a cross-reactive response, and whether this response could alter B104. 1.1 tumour growth. Both humoral and cellular cross-reactive responses were observed, which were capable of inhibiting tumour growth in vivo. This cross-reactive response may be relevant to the immunotherapy of HER2-expressing tumours in humans.
Assuntos
Genes erbB-2 , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/terapia , Receptor ErbB-2/imunologia , Células 3T3 , Animais , Formação de Anticorpos , Divisão Celular , Linhagem Celular Transformada , Reações Cruzadas , Humanos , Imunoterapia , Camundongos , Camundongos Endogâmicos , Neoplasias Experimentais/patologia , Ratos , Receptor ErbB-2/biossíntese , TransfecçãoRESUMO
Internalization of rotavirus in MA104 cells was found to induce coentry of alpha-sarcin, a toxin that inhibits translation in cell-free systems and to which cells are normally impermeable. Entry of the toxin, measured by inhibition of protein synthesis at early times after infection, correlated with virus penetration leading to expression of infectivity, since toxin entry (1) was induced only by trypsin-treated triple-layered virions, to a degree dependent on the toxin and the virus concentration; (2) correlated with the degree of permissivity of different cell lines to rotavirus infection; (3) was inhibited to a similar extent as infectivity by treatment of cells with neuraminidase; and (4) was inhibited by pre- or postadsorption incubation of the virus with neutralizing monoclonal antibodies to VP7 and VP4 (VP8*). Neither the virus infectivity nor the toxin coentry was significantly affected by treatment of cells with bafilomycin A1, an inhibitor of the vacuolar proton ATPase, indicating that both events are independent of the endosomal acid pH. Virus-like particles (VLP), composed of rotavirus proteins 2/6/7/4, but not 2/6/7 or 2/6, were able to induce toxin entry as efficiently as virions. Use of genetically modified VLP in combination with the toxin coentry assay, which measures entry through a productive pathway, should allow identification of the regions of the outer capsid proteins essential for rotavirus penetration.
Assuntos
Endorribonucleases/fisiologia , Proteínas Fúngicas , Rotavirus/fisiologia , Replicação Viral , Animais , Linhagem Celular , Regulação Viral da Expressão Gênica , Humanos , Biossíntese de Proteínas , Inibidores da Síntese de ProteínasRESUMO
The neu proto-oncogene encodes a plasma membrane protein belonging to the epidermal growth factor receptor family. The cell line B104, derived from BDIX rat neuroblastoma, carries a point mutation in neu, and forms a tumor when injected into these rats. The human homologue of the neu oncogene (here called HER2) is overexpressed in certain types of cancer. Rats were immunized with HER2 protein (HER2) to investigate a possible cross-reaction between the homologous proteins which could protect them against subsequent inoculation with B104. Specific antibody in the serum was measured by cell-based enzyme-linked immunoabsorbent assay and fluorescence immunocytochemistry, and delayed-type hypersensitivity by an ear assay. Sera from animals immunized with the HER2 extracellular domain (HER2-ECD) reacted with both HER2- and neu-expressing cells. In the ear assay, a significant cellular response to both HER-ECD (P < 0.05) and neu protein (P < 0.001) was observed in HER2-ECD-immunized rats. However, the growth of B104 tumors in rats was not affected by preimmunization with HER2-ECD. The results indicate that an autoreactive immune response to neu was induced by immunization with HER2-ECD, but was too weak to affect the growth of the neu-bearing tumor.