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1.
J Gen Virol ; 96(9): 2806-2821, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26023150

RESUMO

We report here the complete genome sequence of raccoonpox virus (RCNV), a naturally occurring North American poxvirus. This is the first such North American sequence to the best of our knowledge, and the data showed that RCNV forms a new phylogenetic branch between orthopoxviruses and Yoka poxvirus. RCNV shared overall similarity in genome organization with orthopoxviruses, and the proteins in the central conserved region shared approximately 90  % amino acid identity with orthopoxviruses. RCNV proteins shared approximately 81  % amino acid identity with Yokapox virus proteins. RCNV is missing 10 genes normally conserved in orthopoxviruses, most of which are implicated in virulence. These gene deletions may explain the attenuated phenotype of RCNV in mammals. RCNV contained one unique genome region containing approximately 1 kb of DNA sequence that is not present in any reported poxvirus. It contained a unique ORF predicted to encode a protein with a transmembrane domain. RCNV replicates well in mammalian cells, is naturally attenuated and has been shown to be effective as a vaccine vector platform, so we further tested its safety. We showed here that RCNV is substantially more attenuated than even the highly attenuated VACV-A35Del mutant virus in pregnant, nude and severe combined immunodeficient (SCID) mouse models. RCNV was much safer in pregnant mice and was cleared rapidly from tissues, even in immunocompromised animals, whereas the VACV-A35Del mutant retains virulence and persists in tissues. Thus, RCNV is expected to be a superior vaccine vector for infectious diseases and cancer due to its excellent safety profile, reported vaccine efficacy and ability to replicate in mammalian cells.


Assuntos
Genoma Viral , Orthopoxvirus/genética , Orthopoxvirus/patogenicidade , Infecções por Poxviridae/virologia , Animais , Sequência de Bases , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Camundongos SCID , Dados de Sequência Molecular , América do Norte , Fases de Leitura Aberta , Orthopoxvirus/classificação , Orthopoxvirus/imunologia , Filogenia , Infecções por Poxviridae/imunologia , Gravidez , Linfócitos T/imunologia , Linfócitos T/virologia , Vaccinia virus/genética , Vaccinia virus/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologia , Virulência
2.
Virus Genes ; 50(2): 303-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25645905

RESUMO

Twelve complete African swine fever virus (ASFV) genome sequences are currently publicly available and these include only one sequence from East Africa. We describe genome sequencing and annotation of a recent pig-derived p72 genotype IX, and a tick-derived genotype X isolate from Kenya using the Illumina platform and comparison with the Kenya 1950 isolate. The three genomes constitute a cluster that was phylogenetically distinct from other ASFV genomes, but 98-99 % conserved within the group. Vector-based compositional analysis of the complete genomes produced a similar topology. Of the 125 previously identified 'core' ASFV genes, two ORFs of unassigned function were absent from the genotype IX sequence which was 184 kb in size as compared to 191 kb for the genotype X. There were multiple differences among East African genomes in the 360 and 110 multicopy gene families. The gene corresponding to 360-19R has transposed to the 5' variable region in both genotype X isolates. Additionally, there is a 110 ORF in the tick-derived genotype X isolate formed by fusion of 13L and 14L that is unique among ASFV genomes. In future, functional analysis based on the variations in the multicopy families may reveal whether they contribute to the observed differences in virulence between genotpye IX and X viruses.


Assuntos
Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/isolamento & purificação , Febre Suína Africana/virologia , Genoma Viral , Vírus da Febre Suína Africana/classificação , Animais , Sequência de Bases , Genótipo , Quênia , Dados de Sequência Molecular , Fases de Leitura Aberta , Filogenia , Suínos
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