RESUMO
Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.
Assuntos
Animais , Cães , Humanos , Camundongos , Células A549 , Proteínas Reguladoras de Apoptose/imunologia , Proteína DEAD-box 58/imunologia , Células HEK293 , Vírus da Influenza A Subtipo H1N1/imunologia , Células Madin Darby de Rim Canino , Camundongos Knockout , Infecções por Orthomyxoviridae/patologia , Proteólise , Transdução de Sinais/imunologia , Células THP-1 , Fator 3 Associado a Receptor de TNF/imunologia , Ubiquitinação/imunologia , Proteínas Virais/imunologiaRESUMO
@# Objective To explore the effect of Tuina combined with treadmill training on nerve regeneration after sciatic nerve transection. Methods Ninty-six Sprague-Dawley rats were randomly divided into normal group (n=32), model group (n=32) and treatment group (n=32). The sciatic nerve was transected and the epineurium was sutured in the latter two groups. The treatment group was given Tuina manipulation and treadmill training once a day. Eight rats from each group were detected their sciatic nerve conduction velocity (NCV), the number of axons and Schwann cells (SCs) two, three, four and eight weeks after intervention. Results Compared with the model group, the NCV accelerated in the treatment group four and eight weeks after intervention (P<0.05); while the number of axons was significantly different two and four weeks after intervention (P<0.05), and the number of SCs was not very different between the treatment group and the model group after intervention (P>0.05). Conclusion Tuina combined with treadmill training may promote the regeneration of peripheral nerve after injury in rats.