Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Feb 1;14(2):e1006787.
doi: 10.1371/journal.ppat.1006787. eCollection 2018 Feb.

TRIM proteins: New players in virus-induced autophagy

Konstantin M J Sparrer  1 , Michaela U Gack  1
Affiliations

TRIM proteins: New players in virus-induced autophagy

Konstantin M J Sparrer et al. PLoS Pathog. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. TRIM proteins modulate virus-induced autophagy.
TRIM proteins have at least two different modes of action during virus-induced autophagy. They can act as autophagy receptors that specifically recognize and target viral components for autophagolysosomal degradation (exemplified here by TRIM5α [A]), or they regulate the activity of key autophagy molecules (exemplified here by TRIM23 [B]). (A) After infection of a cell with HIV-1, TRIM5α binds to the capsid of HIV-1, inducing premature capsid disassembly and virus restriction. Both proteasomal (not illustrated) and autophagosomal degradative mechanisms reportedly play a role in viral capsid protein (p24) degradation. For autophagic clearance, the p24-TRIM5α complex is recruited to nucleated autophagosomes, where TRIM5α induces autophagy in a Beclin-1- and ULK1-dependent manner. (B) Upon infection by diverse viral pathogens (e.g., HSV-1, SINV, adenovirus), the E3 ligase activity of TRIM23 is induced, which leads to atypical K27-linked auto-polyubiquitination of its C-terminal ARF domain. This modification triggers GTP-GDP cycling of the TRIM23 ARF GTPase, which, upon binding of TRIM23 to TBK1, induces dimerization and trans-autophosphorylation of TBK1 and, thereby, activation of the kinase. Activated TBK1 then phosphorylates the autophagy receptor p62 at specific serine residues, which allows p62 to recognize specific cargos, such as viral proteins, ultimately triggering their degradation via the lysosome. ARF, ADP ribosylation factor; Auto-K27-polyUb, auto-K27-linked polyubiquitination; E3, E3 ubiquitin ligase; GTP-GDP, guanosine triphosphate-guanosine diphosphate; HSV-1, herpes simplex virus type 1; P, phosphorylation; SINV, Sindbis virus; TBK1, TANK-binding kinase 1; TRIM, tripartite motif; ULK1, Unc-51-like autophagy activating kinase 1; Ub, ubiquitin.
See this image and copyright information in PMC

References

    1. Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132: 27–42. doi: 10.1016/j.cell.2007.12.018 - DOI - PMC - PubMed
    1. Stolz A, Ernst A, Dikic I (2014) Cargo recognition and trafficking in selective autophagy. Nat Cell Biol 16: 495–501. doi: 10.1038/ncb2979 - DOI - PubMed
    1. Deretic V, Saitoh T, Akira S (2013) Autophagy in infection, inflammation and immunity. Nat Rev Immunol 13: 722–737. doi: 10.1038/nri3532 - DOI - PMC - PubMed
    1. Tal MC, Iwasaki A (2009) Autophagy and innate recognition systems. Curr Top Microbiol Immunol 335: 107–121. doi: 10.1007/978-3-642-00302-8_5 - DOI - PubMed
    1. Paul P, Munz C (2016) Autophagy and Mammalian Viruses: Roles in Immune Response, Viral Replication, and Beyond. Adv Virus Res 95: 149–195. doi: 10.1016/bs.aivir.2016.02.002 - DOI - PubMed

Substances