RESUMO
A regional epidemic of aseptic meningitis caused by echovirus 30 (E30) occurred in Hokkaido, Japan, during the period of August-December 2017. To investigate their phylogenetic relationship to other human enteroviruses, we determined the complete genomic nucleotide sequences of isolates from this outbreak. Phylogenetic analysis of the viral capsid protein 1 gene showed that the strains were most closely related to E30 strains detected in Germany, France, and Russia in 2013. In contrast, the region encoding the viral protease and the RNA-dependent RNA polymerase had a close phylogenetic relationship to non-E30 enteroviruses detected in the United Kingdom and Switzerland in 2015-2017, suggesting that a recombination event had occurred.
Assuntos
Infecções por Echovirus/virologia , Enterovirus Humano B/genética , Meningite Asséptica/virologia , Proteínas do Capsídeo/genética , Surtos de Doenças , Infecções por Enterovirus/virologia , Epidemias , França , Genótipo , Alemanha , Humanos , Japão , Epidemiologia Molecular/métodos , Filogenia , RNA Viral/genética , Federação Russa , Análise de Sequência de DNA/métodos , Suíça , Reino UnidoRESUMO
Strains of measles virus of genotypes D5, H1, D4, D8, and B3 were detected among epidemic, endemic, imported and import-associated cases in Hokkaido district, Japan, during 2006-2015. In the present study, their antigenic features were evaluated by determining the complete nucleotide sequences of their hemagglutinin proteins, which are a major target for neutralizing antibodies, and their amino acid sequences deduced. It was found that the hemagglutinin proteins of these strains had several novel amino acid changes in some functional regions. Although these strains have not caused further infections thus far, these antigenic changes should continue to be monitored to maintain their elimination status.
Assuntos
Variação Genética/genética , Hemaglutininas Virais/genética , Hemaglutininas Virais/imunologia , Vírus do Sarampo/genética , Sarampo/imunologia , Sarampo/virologia , Sequência de Aminoácidos , Anticorpos Neutralizantes , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos Virais/genética , Antígenos Virais/imunologia , Evolução Molecular , Genótipo , Humanos , Japão/epidemiologia , Sarampo/epidemiologia , Vírus do Sarampo/classificação , Epidemiologia Molecular , Testes de Neutralização , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/imunologia , Filogenia , Análise de Sequência de DNA , Proteínas Virais/genéticaRESUMO
We determined four complete nucleotide sequences of echovirus 6 (E6) isolated from an epidemic of aseptic meningitis (AM) in Hokkaido, Japan, in 2011. Phylogenetic analysis of the genes encoding viral capsid protein 1 revealed that the strains were closely related to E6 strains isolated in China in recent years, but they were distantly related to E6 strains isolated from patients with AM in Osaka Prefecture, Japan, in 2011. The genes encoding the viral protease and RNA-dependent RNA polymerase (3CD) were closely related to those of several non-E6 strains of the species Human enterovirus B isolated in China, South Korea, and Australia from 1999 to 2010, resulting in a novel cluster in the phylogenetic tree. These results suggest that the incidence of AM in Japan in 2011 was caused by at least two lineages of E6 strains, and a lineage of the 3CD gene was interspersed among different serotypic strains isolated in Western Pacific countries.
Assuntos
Echovirus 6 Humano/genética , Infecções por Echovirus/virologia , Genoma Viral , Meningite Asséptica/virologia , Meningite Viral/virologia , Sequência de Aminoácidos , Sequência de Bases , Pré-Escolar , Sequência Conservada , Echovirus 6 Humano/classificação , Echovirus 6 Humano/isolamento & purificação , Infecções por Echovirus/epidemiologia , Humanos , Japão/epidemiologia , Meningite Asséptica/epidemiologia , Meningite Viral/epidemiologia , Dados de Sequência Molecular , Filogenia , RNA Viral/química , RNA Viral/isolamento & purificação , Proteínas não Estruturais Virais/genéticaRESUMO
Putative animal reservoirs and environmental samples were studied to investigate potential routes of transmission for indigenous hepatitis E virus (HEV) infection in Hokkaido, Japan. A total of 468 liver samples and 954 environmental samples were collected from 2003 to 2011 for this study. Four swine livers (1 %) were positive for HEV RNA; two strains belonged to genotype 3 and the other two strains were genotype 4. Genotype 3 HEV was detected in a sewage sample and a seawater sample. HEV strains derived from swine liver, seawater and raw sewage samples shared 93-100 % sequence similarity with human HEV strains.
Assuntos
Variação Genética , Vírus da Hepatite E/genética , Hepatite E/veterinária , Doenças dos Suínos/virologia , Animais , Sequência de Bases , Cervos , Reservatórios de Doenças/virologia , Microbiologia de Alimentos , Genótipo , Hepatite E/epidemiologia , Hepatite E/virologia , Vírus da Hepatite E/classificação , Humanos , Japão/epidemiologia , Fígado/virologia , Dados de Sequência Molecular , Norgestrel/análogos & derivados , Ostreidae/virologia , Filogenia , RNA Viral/isolamento & purificação , Rios/virologia , Água do Mar/virologia , Esgotos/virologia , Suínos , Doenças dos Suínos/epidemiologiaRESUMO
Hepatitis E virus (HEV) infection is a global public health concern. Although HEV infection is usually asymptomatic and self-limiting, extrahepatic manifestations and chronic infections in immunocompromised patients have been described. HEV strains infecting humans have been classified into four main genotypes. In this study we have developed and validated a novel sensitive real-time RT-PCR assay for the detection of all four HEV genotypes. Simultaneous discrimination of genotypes 1, 2, and 4 from genotype 3 by single nucleotide polymorphism (SNP) analysis was possible. In all, 201 serum samples from cases and carriers previously tested for HEV by nested RT-PCR were analyzed. Twenty-seven HEV-positive samples could not be typed by the nested RT-PCR and nucleotide sequencing, but were newly typed by SNP analysis. As polymorphisms were present at the primer or probe binding site, we adopted a degenerate primer and mixed probes. When a mixed probe was added, the fluorescence intensity increased, facilitating genotype determination. IMPORTANCE The distribution of HEV-3 and HEV-4 has been changing. HEV-4, which had been predominantly found in Asia, is now being detected in other parts of the world, and there are now reports of chronic infections. Additionally, neurological disorders have frequently been reported in patients with acute or chronic HEV infections. HEV-4 has also been shown to lead to a higher severity in terms of acute hepatitis than does HEV-3. Early typing can provide useful information regarding the route of infection and for tailoring treatment to the expected course of the disease. The present method afforded a good detection rate even when polymorphisms were present within the target region for viral gene detection. We believe that this method can be applied to the analysis of mutation-prone viral genes in the future.
Assuntos
Genótipo , Vírus da Hepatite E/genética , Hepatite E/diagnóstico , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real/métodos , Ásia , Sequência de Bases , Técnicas de Genotipagem , Hepatite E/virologia , Humanos , RNA Viral/análiseRESUMO
BACKGROUND: Infection with hepatitis E virus (HEV) genotypes 3 and 4 are usually asymptomatic but can occasionally result in life-threatening acute hepatitis. To date, only sporadic cases together with a few outbreaks have been documented. Seroprevalence studies with assays for the detection of HEV IgG antibodies, suggest that HEV is more prevalent than previously thought, even in non-endemic regions. OBJECTIVES: The aim of this study was to characterize an outbreak of hepatitis E (HE) in a nursing home for aged people between February and March 2016. STUDY DESIGN: After the identification of two cases living in the same nursing home, the presence of antibodies against HEV and HEV RNA were examined in serum samples collected from the other residents and staff members to identify any additional cases. An epidemiological investigation was also carried out. RESULTS: Only 4 patients showed mild symptoms such as anorexia, abdominal pain and fatigue. Among the 125 persons tested, 28 residents and one dietitian were confirmed positive for anti-HEV IgA or IgM antibodies, and/or HEV RNA. Eight samples had only IgG antibodies. Finally, 22 cases were notified with HE on the basis of the presence of IgA antibodies. All HEV isolates obtained were 99.8-100% identical and belonged to genotype 3. CONCLUSION: HEV infections seem to be under-reported or underestimated possibly due to cases being generally asymptomatic. Testing for the presence of both anti-HEV antibodies and HEV RNA would be beneficial for both the comprehensive diagnosis of HE infections and the prevention of further infections.
Assuntos
Surtos de Doenças , Vírus da Hepatite E/isolamento & purificação , Hepatite E/epidemiologia , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Casas de Saúde/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Notificação de Doenças , Feminino , Genótipo , Anticorpos Anti-Hepatite/sangue , Hepatite E/diagnóstico , Vírus da Hepatite E/classificação , Vírus da Hepatite E/genética , Vírus da Hepatite E/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Japão/epidemiologia , Masculino , Prevalência , RNA Viral/sangue , RNA Viral/genética , Estudos SoroepidemiológicosRESUMO
Measles is an acute and highly contagious disease caused by measles virus (MeV). The government of Japan, following the last epidemic in 2007 and 2008, which was caused by genotype D5 strains, introduced a catch-up-vaccination program for teenagers during Japan fiscal years 2008-2012 and a mandatory case-based reporting system for the nationwide elimination. Furthermore, laboratory confirmation of measles cases by genotyping of isolates has been performed to clarify the source of infection and support the interruption of measles cases. Owing to these preventive measures, the number of measles cases has been steadily decreasing after the last epidemic. In March 2015, Japan was internationally verified as having achieved measles elimination by the World Health Organization Regional Office for the Western Pacific. The continuous elimination of measles and high levels of vaccination coverage for MeV have been maintained nationally. However, imported or import-associated cases of measles have sporadically occurred during this time. After the last nationwide epidemic, 17 imported or import-associated measles cases (MeV strains identified as genotypes H1, D4, D8, and B3) were reported in Hokkaido, the northern islands of Japan. In this study, we present the occurrence of measles and surveillance activities in Hokkaido during 2006-2015.
Assuntos
Controle de Doenças Transmissíveis/métodos , Genótipo , Vírus do Sarampo/classificação , Vírus do Sarampo/isolamento & purificação , Sarampo/epidemiologia , Sarampo/virologia , Criança , Pré-Escolar , Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/virologia , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Japão/epidemiologia , Masculino , Vírus do Sarampo/genéticaRESUMO
p73 has a high degree of structural homology to p53 and can activate transcription of p53-responsive genes. However, analysis of p73-deficient mice revealed a marked divergence in the physiological activities of p53 family genes and distinguishes p73 from p53. Mice deficient for p73 exhibit profound defects, including hippocampal dysgenesis, chronic infection, and inflammation, as well as abnormalities in pheromone sensory pathways. p73 plays important roles in neurogenesis, sensory pathways, and homeostatic regulation. Here, we found that the interleukin 4 receptor alpha (IL-4Ralpha) gene is up-regulated by p73 but not significantly by p53 in several human cancer cell lines. IL-4Ralphatranscription is also activated in response to cisplatin, a DNA-damaging agent known to induce p73. By using small interference RNA designed to target p73, we demonstrated that silencing endogenous p73 abrogates the induction of the IL-4Ralpha gene after cisplatin treatment. Furthermore, we identified a p73-binding site in the first intron of the IL-4Ralpha gene that can directly interact with the p73 protein in vivo. This p73-binding site consists of eight copies of a 10-bp consensus p53-binding motif and is a functional response element that is relatively specific for p73 among the p53 family. p73beta promoted localized nucleosomal acetylation through recruitment of coactivator p300, indicating that p73 regulates transcription of IL-4Ralpha through the unique p73-binding site. We also found that p73beta-transfected tumor cells are sensitive to IL-4-mediated apoptosis. Our data suggest that IL-4Ralpha could mediate, in part, certain immune responses and p73-dependent cell death.
Assuntos
Proteínas de Ligação a DNA/fisiologia , Proteínas Nucleares/fisiologia , Receptores de Interleucina-4/genética , Acetilação , Apoptose/efeitos dos fármacos , Apoptose/genética , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Cisplatino/farmacologia , Sequência Consenso , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Genes Supressores de Tumor , Histonas/metabolismo , Humanos , Interleucina-4/farmacologia , Íntrons , Dados de Sequência Molecular , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Regiões Promotoras Genéticas , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores de Interleucina-4/biossíntese , Transativadores/metabolismo , Ativação Transcricional , Transfecção , Proteína Tumoral p73 , Proteínas Supressoras de TumorRESUMO
Tumor suppressor p53 is a transcription factor that induces growth arrest and/or apoptosis in response to cellular stress. To identify novel p53-inducible genes, we compared the expression of genes in normal mouse embryo fibroblasts (MEFs) to p53-null cells by cDNA representational difference analysis. We report here that expression of endogenous sodium channel subunit beta 3 (SCN3B) is upregulated in mouse embryonic fibroblasts by DNA damage in a p53-dependent manner. In addition, we found that SCN3B levels are upregulated in human cancer cell lines by DNA damaging agents, as well as by overexpression of p53, but not significantly by p63 or p73. Furthermore, we identified two putative p53-binding sites upstream of the first exon (RE1) and in the third intron (RE2). The p53 protein can directly interact with the putative p53-binding sites in vivo, as assessed by chromatin immunoprecipitation. A reporter gene assay revealed that these two p53-binding sites are functional response elements. The SCN3B protein appears to be localized to the endoplasmic reticulum (ER). Introduction of the SCN3B gene into T98G and Saos2 cells potently suppressed colony formation. Furthermore, we found that adenovirus-mediated transfer of SCN3B induced apoptosis when combined with anticancer agents. The results presented here suggest that SCN3B mediates a p53-dependent apoptotic pathway and may be a candidate for gene therapy combined with anticancer drugs.
Assuntos
Apoptose/genética , Canais de Sódio/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Éxons/genética , Fibroblastos , Terapia Genética , Humanos , Íntrons/genética , Camundongos , Camundongos Knockout , Canais de Sódio/metabolismo , Proteína Supressora de Tumor p53/deficiência , Proteína Supressora de Tumor p53/genética , Subunidade beta-3 do Canal de Sódio Disparado por VoltagemRESUMO
We report the epidemiology and laboratory diagnostic results of rubella cases from 2011 to 2013 in Hokkaido district, Japan. A total of 150 cases were officially reported as rubella; 102 (68%) involved males and 48 (32%) involved females. The highest proportion of cases were notified in 40-49-year-old age group among males and the 20-29-years-old age group among females. Forty-six cases (25 males and 21 females) had not been vaccinated, and 17 had been vaccinated, whereas 87 had the unknown vaccination status. Eighty-three cases (55.3%) showed the 3 typical principal rubella symptoms (fever, rash, and lymphadenopathy). Seven, 11, 92, and 40 cases were identified in the northern, eastern, central, and southern areas of Hokkaido district, respectively. In the central and southern areas of Hokkaido district, endemic rubella transmissions were indicated by both the epidemiological survey and molecular analyses. However, these outbreaks terminated spontaneously and did not expand to other areas of Hokkaido district. Fortunately, no congenital rubella syndrome (CRS) cases were reported during this observation period. However, to control virus transmission, prevent CRS, and maintain the routine vaccination program, the immediate introduction of an immunization strategy is required for susceptible individuals, particularly young adults.
Assuntos
Técnicas de Laboratório Clínico/métodos , Surtos de Doenças , Rubéola (Sarampo Alemão)/diagnóstico , Rubéola (Sarampo Alemão)/epidemiologia , Adolescente , Adulto , Anticorpos Antivirais/sangue , Sangue/virologia , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Técnicas Imunoenzimáticas , Imunoglobulina M/sangue , Lactente , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Faringe/virologia , Filogenia , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rubéola (Sarampo Alemão)/patologia , Vírus da Rubéola/genética , Vírus da Rubéola/isolamento & purificação , Análise de Sequência de DNA , Homologia de Sequência , Urina/virologia , Adulto JovemRESUMO
Laboratory diagnoses for measles were performed in a total of 97 cases in Hokkaido, Japan, during 2011-2012. Two patients were confirmed to be positive for measles virus (MV), both of whom lived in the Iburi district of Hokkaido. Molecular analysis of the nucleotide sequences of the nucleoprotein (N) gene revealed that these 2 strains had high homology with each other and belonged to the genotype D8. The onset interval of these cases and epidemiological data suggested that MV transmission had occurred between them and then terminated. Phylogenetic analysis of the N gene revealed that the strains identified in Hokkaido were classified into a cluster that contained many genotype D8 strains that were detected within a large area of Japan. Eventually, 9 cases were officially reported as measles. However, other than the abovementioned 2 cases, no genetic information regarding MV was obtained. In future, further active surveillance combined with the genetic investigation should be required in all suspected measles cases to verify the elimination status.
Assuntos
Sarampo , Adulto , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina M/sangue , Lactente , Japão/epidemiologia , Masculino , Sarampo/diagnóstico , Sarampo/epidemiologia , Sarampo/prevenção & controle , Sarampo/virologia , Vacina contra Sarampo , Vírus do Sarampo/classificação , Vírus do Sarampo/genética , Pessoa de Meia-Idade , FilogeniaAssuntos
Infecções por Caliciviridae , Surtos de Doenças , Gastroenterite , Sapovirus , Adolescente , Adulto , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Proteínas do Capsídeo/genética , Pessoas com Deficiência , Gastroenterite/epidemiologia , Gastroenterite/virologia , Instalações de Saúde , Humanos , Japão/epidemiologia , Filogenia , Sapovirus/classificação , Sapovirus/genética , Sapovirus/isolamento & purificação , Análise de Sequência de DNA , Adulto JovemAssuntos
Abate de Animais , Vírus da Influenza A/patogenicidade , Influenza Aviária/epidemiologia , Influenza Humana/etiologia , Laboratórios/estatística & dados numéricos , Aves Domésticas/virologia , Animais , Galinhas/virologia , Humanos , Vírus da Influenza A/classificação , Influenza Aviária/transmissão , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Japão/epidemiologia , Vírus ReordenadosRESUMO
The rapid determination system of viral genome sequences (the RDV method) consists of detecting and determining the nucleotide sequences of viral genomes without using specific primers. To evaluate the usefulness of the RDV method, the detection of human norovirus (NV) genomes in stool specimens was investigated. In addition, the effect of nuclease treatment of the process was examined. A total of 23 human stool specimens were used, all of which were collected from patients with acute viral gastroenteritis, and were shown to contain NV genomes and also determined the cDNA copy numbers by the real-time reverse transcriptase-polymerase chain reaction. NV genomes were detected by the RDV method with nuclease treatment in nine specimens containing cDNA copies ranging between 6.2×10(9) and 9.8×10(11)/g stool. In contrast, NV genome was found by the method in 15 specimens without nuclease treatment and the number of NV cDNA copies ranged between 1.2×10(6) and 9.8×10(11)/g stool. These results suggest that the RDV method has potential for detecting viral genomes in stool specimens. The procedure without a step of nuclease treatment appears to be sensitive.
Assuntos
Infecções por Caliciviridae/diagnóstico , Fezes/virologia , Gastroenterite/virologia , Genoma Viral , Norovirus/isolamento & purificação , Análise de Sequência de DNA/métodos , Infecções por Caliciviridae/virologia , Humanos , Dados de Sequência Molecular , Norovirus/genética , RNA Viral/genética , Carga ViralRESUMO
Noroviruses are important human pathogens which cause epidemic acute viral gastroenteritis. Current techniques used for detection of noroviruses in fecal specimens involve multi-step viral RNA extraction and purification followed by reverse transcriptase-polymerase chain reaction (RT-PCR). This study demonstrates a method for easy detection of norovirus in fecal specimens, involving one-step RNA release and direct use of the released RNA for RT-PCR (direct RT-PCR). For one-step RNA release, a simple method was adopted based on addition of the sample treatment reagent from a commercialized Norovirus GI and GII RNA Detection Kit to suspended fecal specimens, followed by a brief heat treatment. The released RNA was then added directly to the RT mixture from the same kit. After reverse transcription and PCR, the product was detected by agarose gel electrophoresis. Direct RT-PCR was evaluated with 275 fecal specimens comprising 230 norovirus-positive and 45 norovirus-negative samples as assessed by real-time RT-PCR, considered to be the "gold standard" for norovirus detection. Direct RT-PCR was sufficiently specific and sensitive for norovirus detection, and eliminated the RNA extraction and purification step. Use of this method should facilitate detection of norovirus in fecal specimens and provide valuable information regarding the incidence of the virus. In addition, this method should be applicable for other RNA viruses.
Assuntos
Infecções por Caliciviridae/diagnóstico , Fezes/virologia , Gastroenterite/virologia , Norovirus/isolamento & purificação , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Eletroforese em Gel de Ágar , Humanos , Norovirus/genética , RNA Viral/isolamento & purificação , Sensibilidade e EspecificidadeAssuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/transmissão , Surtos de Doenças/estatística & dados numéricos , Sarampo/epidemiologia , Sarampo/transmissão , Adolescente , Adulto , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Conventional reverse transcription-polymerase chain reaction (RT-PCR) to detect norovirus (NV) is a complex of multi-step procedure that requires gel electrophoresis as well as hybridization or sequencing to confirm the final diagnosis. A duplex TaqMan RT-PCR was developed to detect and classify genogroup (G) I and GII of NV. The primers and TaqMan probes for this assay were selected from the region of open reading frame (ORF) 1-ORF2 junction. A total of 796 stool specimens from 103 outbreaks of gastroenteritis, and a series of 46 stool specimens containing most NV genotypes was used for this study. For these specimens from 103 outbreaks, NV was detected and classified by the duplex TaqMan RT-PCR in 536 of the 541 specimens tested previously to be positive using the conventional RT-PCR. Two hundred fifty-one of the 255 specimens that were negative by the conventional RT-PCR were also negative by the TaqMan RT-PCR. No false positive result was observed for other enteric RNA viruses such as rotavirus and sapovirus. This is the first report on the development of a duplex TaqMan RT-PCR end-point assay for detection and differentiation of GI and GII of NV strains simultaneously followed by genotyping. These results suggest the practical application of this duplex TaqMan RT-PCR is useful for the detection of NV in clinical specimens.
Assuntos
Infecções por Caliciviridae/diagnóstico , Gastroenterite/virologia , Norovirus/classificação , Norovirus/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sequência de Bases , Infecções por Caliciviridae/epidemiologia , Primers do DNA/genética , Surtos de Doenças , Fezes/virologia , Gastroenterite/epidemiologia , Genótipo , Humanos , Dados de Sequência Molecular , Norovirus/genética , RNA Viral/genética , Sensibilidade e Especificidade , Alinhamento de SequênciaRESUMO
E1AF was first identified as a transcription factor that binds to enhancer motifs of the adenovirus E1A gene and is thought to be a human homologue of mouse PEA3, one of the ets oncoprotein families. Here we show the effect of E1A on the gene expression and function of E1AF. E1A repressed the activity of E1AF promoter, and the N-terminal region of E1A, which is involved in the oncogenic activity of E1A, was essential for this repression. The ability as a transcription factor of E1AF, as well as those of the other PEA3 subfamily members ER81 and ERM, was also repressed by E1A via the same oncogenic domain. Furthermore, E1AF repressed the transformation activity of E1A cooperating with E1B, whereas the other ets family Ets-1 enhanced this activity. These results suggest that E1AF is one of the targets of E1A.