IL-6/STAT3 axis is hijacked by GCRV to facilitate viral replication via suppressing type â IFN signaling.

Grass carp reovirus (GCRV) infections and hemorrhagic disease (GCHD) outbreaks are typically seasonally periodic and temperature-dependent, yet the molecular mechanism remains unclear. Herein, we depicted that temperature-dependent IL-6/STAT3 axis was exploited by GCRV to facilitate viral replication via suppressing type Ⅰ IFN signaling. Combined multi-omics analysis and qPCR identified IL-6, STAT3, and IRF3 as potential effector molecules mediating GCRV infection. Deploying GCRV challenge at 18 °C and 28 °C as models of resistant and permissive infections and switched to the corresponding temperatures as temperature stress models, we illustrated that IL-6 and STAT3 expression, genome level of GCRV, and phosphorylation of STAT3 were temperature dependent and regulated by temperature stress. Further research revealed that activating IL-6/STAT3 axis enhanced GCRV replication and suppressed the expression of IFNs, whereas blocking the axis impaired viral replication. Mechanistically, grass carp STAT3 inhibited IRF3 nuclear translocation via interacting with it, thus down-regulating IFNs expression, restraining transcriptional activation of the IFN promoter, and facilitating GCRV replication. Overall, our work sheds light on an immune evasion mechanism whereby GCRV facilitates viral replication by hijacking IL-6/STAT3 axis to down-regulate IFNs expression, thus providing a valuable reference for targeted prevention and therapy of GCRV.

Circumferential Decompression Technique of Posterior Endoscopic Cervical Foraminotomy.

OBJECTIVE: Cervical osseous foraminal stenosis (COFS) results from the uncinate process and facet hyperostosis. Currently, the optimal surgical technique for the treatment of COFS remains controversial. MATERIALS AND METHODS: Patients with COFS presenting radiculopathy underwent posterior endoscopic cervical foraminotomy by the circumferential decompression technique. The neck disability index (NDI), the visual analogue scale (VAS), and the modified MacNab criteria were used to evaluate the outcomes. In addition, the range of motion (ROM) and the slippage distance between the operated vertebrae in flexion-extension position were measured to evaluate the stability of the cervical spine. RESULTS: There were 24 consecutive patients in the study. The mean follow-up period was 16.2 months (range: 12-26 months). The NDI and VAS scores for arm/neck pain improved significantly from preoperatively to the last follow-up. The satisfaction rate by modified MacNab criteria was 91.7% on the third postoperative day and 100% on the day of final follow-up. There were no significant differences in intervertebral ROM or slippage distance between the last follow-up and preoperatively (P = 0.968, P = 0.394). Arm pain occurred in one patient, and sustained fingers numbness in two patients, but these symptoms resolved at the last follow-up. CONCLUSIONS: Posterior endoscopic cervical foraminotomy by the circumferential decompression technique is a safe and effective treatment for COFS. Moreover, it preserves the stability and physiological mobility of the cervical spine.