RESUMO
A class of secreted poxvirus tumor necrosis factor (TNF)-binding proteins has been isolated from Tanapox-infected cell supernatants. The inhibitor bound to a TNF-affinity column and was identified as the product of the 2L gene. Sequence analysis of 2L family members from other yatapoxviruses and swinepox virus yielded no sequence homology to any known cellular gene. The expressed Tanapox virus 2L protein bound to human TNF with high affinity (K(d) = 43 pM) and exhibits an unusually slow off-rate. However, 2L is unable to bind to a wide range of human TNF family members. The 2L protein can inhibit human TNF from binding to TNF receptors I and II as well as block TNF-induced cytolysis. Thus, Tanapox virus 2L represents an inhibitor of human TNF and offers a unique strategy with which to modulate TNF activity.
Assuntos
Proteínas de Transporte/fisiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Proteínas Virais/fisiologia , Yatapoxvirus/fisiologia , Sequência de Aminoácidos , Animais , Antígenos CD/metabolismo , Sequência de Bases , Proteínas de Transporte/genética , Proteínas de Transporte/farmacologia , DNA Viral/genética , Genes Virais , Humanos , Camundongos , Dados de Sequência Molecular , Receptores do Fator de Necrose Tumoral/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral , Receptores Tipo II do Fator de Necrose Tumoral , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Homologia de Sequência de Aminoácidos , Receptores Chamariz do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Virais/genética , Proteínas Virais/farmacologia , Vírus do Tumor do Macaco de Yaba/genética , Vírus do Tumor do Macaco de Yaba/fisiologia , Yatapoxvirus/genéticaRESUMO
The effect of Yaba virus preinfection on DNA synthesis in SV40-infected Jinet cells was studied. Time-course synthesis studies were conducted using the incorporation of labeled thymidine. Yaba virus preinfection resulted in the inhibition of SV40 DNA synthesis when the elapsed time between Yaba virus and SV40 infections was three days. This inhibition was demonstrated by hybridization studies and sedimentation analysis. In addition, the usual stimulation of cellular DNA synthesis induced by SV40 infection was inhibited. This inhibition occurred at a time in Yaba virus infection when no cytoplasmic Yaba virus-specific DNA synthesis occurred.
