RESUMO
Adenoviruses can cause infectious diarrheal disease or respiratory infections in humans; 2 recent reports have indicated probable human infection with simian adenoviruses (SAdVs). To assess the possibility of animal-to-human transmission of SAdVs, we tested fecal samples from asymptomatic rhesus macaques housed in 5 primate facilities in the United States and cultured 23 SAdV isolates. Of these, 9 were purified and completely sequenced; 3 SAdV samples from the American Type Culture Collection (SAdV-6, SAdV-18, and SAdV-20) were also completely sequenced. The sequence of SAdV-18 was closely related to that of human adenovirus F across the whole genome, and the new isolates were found to harbor 2 fiber genes similar to those of human adenovirus (HAdV) strains HAdV-40 and HAdV-41, which can cause infectious diarrhea. The high prevalence of adenoviruses in fecal samples from asymptomatic rhesus macaques and the similarity of the isolates to human strains indicates the possibility of animal-to-human transmission of SAdVs.
Assuntos
Infecções por Adenoviridae/veterinária , Adenovirus dos Símios/isolamento & purificação , Fezes/virologia , Macaca mulatta/virologia , Doenças dos Macacos/transmissão , Zoonoses/transmissão , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/transmissão , Infecções por Adenoviridae/virologia , Adenovirus dos Símios/classificação , Adenovirus dos Símios/genética , Sequência de Aminoácidos , Animais , DNA Viral/genética , DNA Viral/isolamento & purificação , Humanos , Dados de Sequência Molecular , Doenças dos Macacos/epidemiologia , Doenças dos Macacos/virologia , Filogenia , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNA , Estados Unidos/epidemiologia , Zoonoses/epidemiologia , Zoonoses/virologiaRESUMO
The complete nucleotide sequence of an isolate of simian adenovirus 7 (SAdV-7) was determined. The genome organization of this isolate was found to be similar to that of other primate adenoviruses with two principal notable points: severe truncation of the E1A and E1B 19K proteins and an E3 region encoding only the 12.5K homologue. The viral gene products of SAdV-7 are most closely related to simian adenovirus 1 (SAdV-1), and like SAdV-1, are related to the human adenovirus species HAdV-F, such as the enteric adenoviruses HAdV-40 and HAdV-41 and the recently defined HAdV-G (HAdV-52). Two kinds of gene transfer vectors were made: a replication-competent SAdV-7-based vector with no genomic deletion, and a standard replication-incompetent vector deleted for E1. Importantly, the E1-deleted vector could be propagated to high titre by trans-complementation in human HEK 293 cells.
Assuntos
Adenovirus dos Símios/genética , Técnicas de Transferência de Genes/instrumentação , Vetores Genéticos/genética , Adenovirus dos Símios/fisiologia , Sequência de Aminoácidos , Animais , Linhagem Celular , Vetores Genéticos/fisiologia , Humanos , Dados de Sequência Molecular , Replicação ViralRESUMO
The successful use of any adenoviral vectors is predicated upon the use of a serotype that is not neutralized by circulating antibodies. However, efforts to develop a diverse repertoire of serologically distinct adenovirus vectors may be hindered by the necessity to generate cell lines to allow for the successful propagation of vectors deleted of essential genes. A strategy to construct chimeric adenoviruses whereby the rescue and propagation of an E1-deleted HAdV-B-derived adenoviral vector can be achieved using existing cell lines such as HEK 293 is reported. It is further shown that this strategy may be more widely applicable.
Assuntos
Adenovirus dos Símios/genética , DNA Viral/genética , Vetores Genéticos , Genoma Viral , Proteínas E1 de Adenovirus/genética , Proteínas E1 de Adenovirus/imunologia , Proteínas E4 de Adenovirus/genética , Proteínas E4 de Adenovirus/imunologia , Adenovirus dos Símios/classificação , Adenovirus dos Símios/imunologia , Animais , Linhagem Celular , Estudos de Viabilidade , Humanos , Modelos Genéticos , Testes de Neutralização , Pan troglodytes/virologia , Plasmídeos , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Mapeamento por Restrição , Sorotipagem , TransfecçãoRESUMO
In order to elucidate the relative importance of neutralizing determinants on each of the three major adenoviral capsid components, we have generated chimeric vectors where the hexon protein, or the fiber protein, or both hexon and fiber proteins of one serotype (Simian Adenovirus 24/Pan 7) have been replaced by those of another (Simian Adenovirus 23/Pan 6). The effect of each replacement was evaluated by neutralization assays and by attempted vector re-administration into mice. Both hexon and fiber were found to harbor neutralization epitopes although in vivo transduction was more severely affected by anti-hexon antibodies.
Assuntos
Adenovirus dos Símios/genética , Adenovirus dos Símios/imunologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Vetores Genéticos , Animais , Anticorpos Antivirais , Antígenos Virais/genética , Quimera/genética , Quimera/imunologia , Epitopos/genética , Imunização , Técnicas In Vitro , Óperon Lac , Camundongos , Camundongos Endogâmicos BALB C , Testes de NeutralizaçãoRESUMO
The complete nucleotide sequences for four adenoviruses-Simian Adenoviruses 21, 22, 23, and 24, originally isolated from chimpanzees, were determined. The genome organization of the chimpanzee adenoviruses was found to be similar to that of other adenoviruses. The viral gene products of the adenoviruses Simian Adenoviruses 22, 23, and 24 are very closely related to those of the (previously sequenced) chimpanzee adenovirus Simian Adenovirus 25. Simian Adenovirus 21 is most similar to human subgroup B adenoviruses HAdV-3, HAdV-7, and HAdV-35. Analysis of the capsid proteins hexon and fiber of the chimpanzee adenoviruses also supports the placement of Simian Adenovirus 21 in subgroup B and Simian Adenoviruses 22, 23, and 24 in subgroup E.
