Rhesus monkey TRIM5? protein SPRY domain contributes to AP-1 activation.

ABSTRACT: TRIM5? is an important host restriction factor that could potently block retrovirus infection. The SPRY domain of TRIM5? mediates post-entry restriction by recognition of and binding to the retroviral capsid. Human TRIM5? also functions as an innate immune sensor to activate AP-1 and NF-?B signaling, which subsequently restrict virus replication. Previous studies have shown that the AP-1 and NF-?B signaling activation relies on the RING motif of TRIM5?. In this study, we have demonstrated that the SPRY domain is essential for rhesus macaque TRIM5? to activate AP-1 but not NF-?B signaling. The AP-1 activation mainly depends on all of the ?-sheet barrel on SPRY structure of TRIM5?. Furthermore, the SPRY-mediated auto-ubiquitination of TRIM5? is required for AP-1 activation. This study reports that rhesus macaque TRIM5? mainly undergoes Lys27-linked and Met1-linked auto-polyubiquitination. Finally, we found that the TRIM5? signaling function was positively correlated with its retroviral restriction activity. This study discovered an important role of the SPRY domain in immune signaling and antiviral activity and further expanded our knowledge of the antiviral mechanism of TRIM5?.

SUBMITTER: Na L 

PROVIDER: S-EPMC5827426 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature