Retrovirus Restriction by TRIM5α: RINGside at a Cage Fight

Abstract

The restriction factor TRIM5α recognizes incoming retroviral capsids and blocks virus replication. In this issue of Cell Host and Microbe, Fletcher et al. (2018) show how the TRIM5α RING domain mediates formation of various ubiquitin conjugates that differentially regulate TRIM5α turnover, inhibition of viral reverse transcription, and innate immune activation.

To TRIM or not to TRIM: the balance of host–virus interactions mediated by the ubiquitin system

“…Fascinatingly, TRIM5α receives its N-terminal monoubiquitin early, creating a ‘standby’ protein ready for degradation in the absence of infection and higher-order assemblies. This stepwise progression of capsid recognition, higher-order assembly, K63-linked polyubiquitination and NF-κB signalling function as checkpoints, thereby allowing TRIM5α to act as its own antiviral signalling platform with an established criterion system for what is sufficient for activation and signal induction () [140, 141]. TRIM5 has therefore been proposed to act as a PRR by recognizing the retroviral capsid and promoting activation of the TAK1 kinase via synthesis of unanchored K63-linked polyubiquitin chains [63].…”

Regulation of Tripartite Motif-Containing Proteins on Immune Response and Viral Evasion

“…Tripartite motif-containing proteins are able to modulate the TLR signaling pathways ( Shen et al, 2012 ; Hu et al, 2014 ; Sundquist and Pornillos, 2018 ; Ganser-Pornillos and Pornillos, 2019 ). It has been proposed that TRIM5α is implicated in NF-κB signaling pathways and promotes the synthesis of unanchored K63-linked polyubiquitin chains, which can in turn activate the TAK1 ( Sundquist and Pornillos, 2018 ; Ganser-Pornillos and Pornillos, 2019 ). TRIM56 has been shown to interact with TRIF in TLR3-mediated IFN/ISG production ( Shen et al, 2012 ).…”