Assuntos
Proteínas de Bactérias , Proteínas de Membrana/genética , Metiltransferases/genética , Streptococcus/genética , Antibacterianos/farmacologia , Sangue/microbiologia , Resistência Microbiana a Medicamentos/genética , Genótipo , Humanos , Macrolídeos , Fenótipo , Streptococcus/efeitos dos fármacos , Streptococcus/isolamento & purificaçãoRESUMO
Certain viruses have evolved mechanisms to counteract innate immunity, a host response in which nuclear factor kappaB (NF-kappaB) transcription factors play a central role. African swine fever virus encodes a protein of 28.2 kDa containing ankyrin repeats similar to those of cellular IkappaB proteins, which are inhibitors of NF-kappaB. Transfection of the African swine fever virus IkappaB gene inhibited tumor necrosis factor- or phorbol ester-induced activation of kappaB- but not AP-1-driven reporter genes. Moreover, African swine fever virus IkappaB co-immunoprecipitated with p65 NF-kappaB, and the purified recombinant protein prevented the binding of p65-p50 NF-kappaB proteins to their target sequences in the DNA. NF-kappaB activation induced by tumor necrosis factor, as detected by mobility shift assays or by transfection of kappaB-driven reporter genes, is impaired in African swine fever virus-infected cells. These results indicate that the African swine fever virus IkappaB gene homologue interferes with NF-kappaB activation, likely representing a new mechanism to evade the immune response during viral infection.
Assuntos
Vírus da Febre Suína Africana/genética , Proteínas de Ligação a DNA/genética , Genes Virais , Proteínas I-kappa B , NF-kappa B/antagonistas & inibidores , Proteínas Virais/genética , Vírus da Febre Suína Africana/crescimento & desenvolvimento , Sequência de Aminoácidos , Animais , Chlorocebus aethiops , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/farmacologia , Regulação da Expressão Gênica , Genes Reporter , Dados de Sequência Molecular , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Ligação Proteica , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Homologia de Sequência de Aminoácidos , Células Vero/virologia , Proteínas Virais/metabolismo , Proteínas Virais/farmacologiaRESUMO
The tylosin producer Streptomyces fradiae contains four known resistance genes, two of which (tlrA and tlrD) encode methyltransferases that act on ribosomal RNA at a common site. Expression of tlrA is regulated via transcriptional attenuation. A short transcript, only 411 nucleotides long, terminates 27 nucleotides into the methylase-coding sequence in the uninduced state. Induction of tlrA is proposed to involve a ribosome-mediated conformational change within the mRNA leader that allows transcription to continue beyond the attenuation site, resulting in a transcript about 1450 nucleotides long. Transplantation of tlrD and/or tlrA into Streptomyces albus revealed that the induction specificity of tlrA depends upon the state of the ribosomes and is significantly altered in strains also expressing tlrD.