Role of SUMO-1 and SUMO interacting motifs in rhesus TRIM5α-mediated restriction

Retrovirology

Gloria Arriagada²  Edward M Campbell³  Stephen P Goff¹  Zana Lukic³ 

[1] Howard Hughes Medical institute;Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello, Los Fresnos 52, Viña del Mar, Chile;Department of Microbiology and Immunology Stritch School of Medicine, Loyola University Chicago, 2160 S. 1st Ave. 508, Building 102, Room 5651, Maywood, IL, 60153, USA

关键词: HIV-1;    rhTRIM5α;    SIM;    SUMO-1;   

Others  :  1209170
DOI  :  10.1186/1742-4690-10-10

 received in 2012-09-16, accepted in 2013-01-16,  发布年份 2013

【 摘 要 】

Background

TRIM5α is a member of the tripartite motif family of proteins that restricts retroviral infection in a species-specific manner. The restriction requires an interaction between the viral capsid lattice and the B30.2/SPRY domain of TRIM5α. Previously, we determined that two SUMO interacting motifs (SIMs) present in the B30.2/SPRY domain of human TRIM5α (huTRIM5α) were important for the restriction of N-tropic Murine Leukemia Virus. Here, we examined whether SUMO expression and the SIM1 and SIM2 motifs in rhesus monkey TRIM5α (rhTRIM5α) are similarly important for Human Immunodeficiency Type 1 (HIV-) restriction.

Results

We found that mutation of SIM1 and SIM2 of rhTRIM5α abolished the restriction of HIV-1 virus. Further, knockdown of SUMO-1 in rhTRIM5α expressing cells abolished restriction of HIV-1. These results may be due, in part, to the ability of SUMO-1 to stabilize rhTRIM5α protein expression, as SUMO-1 knockdown increased rhTRIM5α turnover and the mutations in SIM1 and SIM2 led to more rapid degradation than the wild type protein. The NF-κB signaling ability of rhTRIM5α was also attenuated by SUMO-1 knockdown. Finally, upon inhibition of CRM1-dependent nuclear export with Leptomycin B (LMB), wild type rhTRIM5α localized to SUMO-1 bodies in the nucleus, while the SIM1 and SIM2 mutants did not localize to SUMO-1.

Conclusions

Our results suggest that the rhTRIM5α B30.2/SPRY domain is not only important for the recognition of the HIV-1 CA, but it is also important for its association with SUMO-1 or SUMO-1 modified proteins. These interactions help to maintain TRIM5α protein levels and its nuclear localization into specific nuclear bodies.

【 授权许可】

   
2013 Lukic et al; licensee BioMed Central Ltd.

【 图 表 】

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