TRIM5α associates with proteasomal subunits in cells while in complex with HIV-1 virions

Retrovirology

Edward M Campbell³  Jeremy Luban¹  Seth L Robia²  Jaya Sastri³  Justin Rucci³  Sarah Sebastian¹  Stéphane Hausmann¹  Zana Lukic³ 

[1] Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland;Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood IL, USA;Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood IL, USA

关键词: immunofluorescence;    cytoplasmic bodies;    proteasomal subunits;    HIV-1;    TRIM5α;   

Others  :  1209385
DOI  :  10.1186/1742-4690-8-93

 received in 2011-08-31, accepted in 2011-11-12,  发布年份 2011

【 摘 要 】

Background

The TRIM5 proteins are cellular restriction factors that prevent retroviral infection in a species-specific manner. Multiple experiments indicate that restriction activity requires accessory host factors, including E2-enzymes. To better understand the mechanism of restriction, we conducted yeast-two hybrid screens to identify proteins that bind to two TRIM5 orthologues.

Results

The only cDNAs that scored on repeat testing with both TRIM5 orthologues were the proteasome subunit PSMC2 and ubiquitin. Using co-immunoprecipitation assays, we demonstrated an interaction between TRIM5α and PSMC2, as well as numerous other proteasome subunits. Fluorescence microscopy revealed co-localization of proteasomes and TRIM5α cytoplasmic bodies. Forster resonance energy transfer (FRET) analysis indicated that the interaction between TRIM5 and PSMC2 was direct. Previous imaging experiments demonstrated that, when cells are challenged with fluorescently-labeled HIV-1 virions, restrictive TRIM5α orthologues assemble cytoplasmic bodies around incoming virion particles. Following virus challenge, we observed localization of proteasome subunits to rhTRIM5α cytoplasmic bodies that contained fluorescently labeled HIV-1 virions.

Conclusions

Taken together, the results presented here suggest that localization of the proteasome to TRIM5α cytoplasmic bodies makes an important contribution to TRIM5α-mediated restriction.

【 授权许可】

   
2011 Lukic et al; licensee BioMed Central Ltd.

【 图 表 】

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