TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2

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.

Clinical characteristics analyses of multiple myeloma with peripheral neuropathy / 白血病·淋巴瘤

Objective To investigate the clinical manifestations and nerve electrophysiological abnormalities of the patients with multiple myeloma peripheral neuropathy (MMPN). Methods The clinical data of 35 patients with MMPN diagnosed in Shanxi Provincial People's Hospital from March 2010 to June 2018 were retrospectively analyzed. All patients received nerve electrophysiology examination, including nerve conductive velocity (NCV) and skin sympathetic response (SSR). Results The most common symptoms of peripheral nerve involvement for MMPN patients were sensory abnormalities (25 cases, 71%), including root pains (3 cases, 9%), pain ablation of the upper or lower limbs (18 cases, 51%), dyskinesia (15 cases, 43%), disappeared or reduced knee or ankle reflex (13 cases, 37%) and automatic sympathetic disorders (20 cases, 57%). Nerve electrophysiological tests showed 29 cases (83%) were involved in abnormal sensory nerve conduction velocity (SCV) or motor nerve conduction velocity (MCV), including 13 cases of upper limb abnormality in NCV, 5 cases of prolonged incubation in upper limb, and 10 cases of decreased amplitude;8 cases of lower limb abnormality in NCV, 6 cases of prolonged incubation in lower limb, and 4 cases of decreased amplitude. SSR test showed abnormalities were found in 17 patients (49%), including 8 cases of upper limb abnormality in SRR, 2 cases of prolonged incubation in upper limb, and 7 cases of decreased amplitude, 1 case of disappeared waveform; 6 cases of lower limb abnormality in SRR, 1 case of prolonged incubation in lower limb, and 4 cases of decreased amplitude, 2 cases of disappeared waveform; 3 cases of abnormal upper and lower limbs. Conclusions The most common peripheral nerve damages of MM are "sock and gloveˉlike" sensory ablation, accompanied with the involvement of automatic nerve damage. NCV is the major method to diagnose MMPN, and SSR plays an important role in the detection of sympathetic nerve damage of MMPN.

Preparation and Identification of Cetuximab-β-Glucosidase Conjugates / 天津医药

Objective To prepare cetuximab-β-glucosidase conjugates and to identify its enzymatic activity and an?tibody activity. Methods Cetuximab andβ-glucosidase were crosslinked by Sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC). Cetuximab-β-glucosidase conjugates and its enzymatic and antibody activity were examined by non-reduced SDS-PAGE, colorimetry and indirect immunofluorescence assay. Results We can see clear bands ofβ-glucosidase, cetuximab, cetuximab-β-glucosidase conjugates through electropherogram. Although the en?zymatic activity of cetuximab-β-glucosidase conjugates was lower than that ofβ-glucosidase (U/L:672.97±46.19 vs 869.50± 57.28,t=5.972,P<0.05) shown by colorimetry assay, it still maintain good enzymatic activity. Under fluorescence micro?scope, we can see the conjugates interacted with human bladder cancer EJ cells are in a red fluorescence. Conclusion Ce?tuximab,β-glucosidase were crosslinked successfully by Sulfo-SMCC without altered its enzymatic and antibody activity.