Retrovirus Restriction by TRIM5α: RINGside at a Cage Fight
| Autor: | Owen Pornillos, Wesley I. Sundquist |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
viruses Cell Ube2N/Ube2V2 restriction factor Virus Replication Microbiology Article 03 medical and health sciences 0302 clinical medicine Retrovirus Capsid Ubiquitin Virology UFD pathway medicine Ring domain innate immunity TRIM5 Ube2W Innate immune system Viral Reverse Transcription biology K63-linked Ub reverse transcription biology.organism_classification Cell biology 030104 developmental biology medicine.anatomical_structure Retroviridae Viral replication biology.protein HIV-1 Parasitology Carrier Proteins 030217 neurology & neurosurgery |
| Zdroj: | Cell Host & Microbe |
| ISSN: | 1934-6069 |
| Popis: | Summary TRIM5 is a RING domain E3 ubiquitin ligase with potent antiretroviral function. TRIM5 assembles into a hexagonal lattice on retroviral capsids, causing envelopment of the infectious core. Concomitantly, TRIM5 initiates innate immune signaling and orchestrates disassembly of the viral particle, yet how these antiviral responses are regulated by capsid recognition is unclear. We show that hexagonal assembly triggers N-terminal polyubiquitination of TRIM5 that collectively drives antiviral responses. In uninfected cells, N-terminal monoubiquitination triggers non-productive TRIM5 turnover. Upon TRIM5 assembly on virus, a trivalent RING arrangement allows elongation of N-terminally anchored K63-linked ubiquitin chains (N-K63-Ub). N-K63-Ub drives TRIM5 innate immune stimulation and proteasomal degradation. Inducing ubiquitination before TRIM5 assembly triggers premature degradation and ablates antiviral restriction. Conversely, driving N-K63 ubiquitination after TRIM5 assembly enhances innate immune signaling. Thus, the hexagonal geometry of TRIM5’s antiviral lattice converts a capsid-binding protein into a multifunctional antiviral platform. Graphical Abstract Highlights • Ubiquitin is redundant for TRIM5 inhibition of viral infection • TRIM5 assembly drives formation of K63-Ub chains anchored to TRIM5 N terminus • Three RING domains are necessary for N-terminal K63-Ub extension • Anchored K63-Ub couples capsid binding with signaling and proteasome recruitment TRIM5 self-assembles into a lattice that envelopes retroviral capsids, stimulating virion destruction and innate immune signaling. Fletcher et al. demonstrate that self-assembly induces K63-linked ubiquitination (K63-Ub) of the TRIM5 N terminus that drives innate immune stimulation and degradation. Thus, ordered capsid binding allows TRIM5 to couple virus recognition with antiviral responses. |
| Databáze: | OpenAIRE |
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