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Título:
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Antiviral chemotherapy facilitates control of poxvirus infections through inhibition of cellular signal transduction
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Autores:
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Yang, Hailin ;
Kim, Sung-Kwon ;
Kim, Mikyung ;
Reche, Pedro A ;
Morehead, Tiara J ;
Damon, Inger K ;
Welsh, Raymond M ;
Reinherz, Ellis L
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Tipo de documento:
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texto impreso
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Editorial:
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American Society for Clinical Investigation, 2005
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Dimensiones:
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application/pdf
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Nota general:
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info:eu-repo/semantics/openAccess
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Idiomas:
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Palabras clave:
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Estado = Publicado
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Materia = Ciencias Biomédicas: Medicina: Inmunología
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Materia = Ciencias Biomédicas: Biología: Microbiología
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Materia = Ciencias: Informática: Bioinformática
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Materia = Ciencias Biomédicas: Biología: Biología molecular
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Tipo = Artículo
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Resumen:
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The EGF-like domain of smallpox growth factor (SPGF) targets human ErbB-1, inducing tyrosine phosphorylation of certain host cellular substrates via activation of the receptor's kinase domain and thereby facilitating viral replication. Given these findings, low molecular weight organic inhibitors of ErbB-1 kinases might function as antiviral agents against smallpox. Here we show that CI-1033 and related 4-anilinoquinazolines inhibit SPGF-induced human cellular DNA synthesis, protein tyrosine kinase activation, and c-Cbl association with ErbB-1 and resultant internalization. Infection of monkey kidney BSC-40 and VERO-E6 cells in vitro by variola strain Solaimen is blocked by CI-1033, primarily at the level of secondary viral spreading. In an in vivo lethal vaccinia virus pneumonia model, CI-1033 alone promotes survival of animals, augments systemic T cell immunity and, in conjunction with a single dose of anti-L1R intracellular mature virus particle-specific mAb, fosters virtually complete viral clearance of the lungs of infected mice by the eighth day after infection. Collectively, these findings show that chemical inhibitors of host-signaling pathways exploited by viral pathogens may represent potent antiviral therapies.
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En línea:
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https://eprints.ucm.es/id/eprint/9333/1/25.YangReche_etal_JCI_2005.pdf
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