RESUMO
Cowpox virus effectively inhibits inflammatory responses against viral infection in the chick embryo. This study demonstrates that one of the viral genes necessary for this inhibition, the crmA gene (a cytokine response modifier gene), encodes a serpin that is a specific inhibitor of the interleukin-1 beta converting enzyme. This serpin can prevent the proteolytic activation of interleukin-1 beta, thereby suppressing an interleukin-1 beta response to infection. However, the modification of this single cytokine response is not sufficient to inhibit inflammatory responses. This suggests that cowpox virus encodes several cytokine response modifiers that act together to inhibit the release of pro-inflammatory cytokines in response to infection. These viral countermeasures to host defenses against infection may contribute significantly to the pathology associated with poxvirus infections.
Assuntos
Vírus da Varíola Bovina/enzimologia , Interleucina-1/metabolismo , Metaloendopeptidases/antagonistas & inibidores , Serina Endopeptidases/metabolismo , Serpinas/genética , Proteínas Virais , Sequência de Aminoácidos , Animais , Sítios de Ligação , Caspase 1 , Embrião de Galinha , Vírus da Varíola Bovina/genética , Vírus da Varíola Bovina/imunologia , Genes Virais , Inflamação/enzimologia , Dados de Sequência Molecular , Processamento de Proteína Pós-Traducional , Proteínas Estruturais Virais/genéticaRESUMO
Interleukin-1 beta (IL-1 beta) mediates a wide range of immune and inflammatory responses. The active cytokine is generated by proteolytic cleavage of an inactive precursor. A complementary DNA encoding a protease that carries out this cleavage has been cloned. Recombinant expression in COS-7 cells enabled the cells to process precursor IL-1 beta to the mature form. Sequence analysis indicated that the enzyme itself may undergo proteolytic processing. The gene encoding the protease was mapped to chromosomal band 11q23, a site frequently involved in rearrangement in human cancers.
