Role of SUMO-1 and SUMO interacting motifs in rhesus TRIM5alpha-mediated restriction Journal Article

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Authors: Lukic, Z.; Goff, S. P.; Campbell, E. M.; Arriagada, G.
Article Title: Role of SUMO-1 and SUMO interacting motifs in rhesus TRIM5alpha-mediated restriction
Abstract: BACKGROUND: TRIM5alpha 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 TRIM5alpha. Previously, we determined that two SUMO interacting motifs (SIMs) present in the B30.2/SPRY domain of human TRIM5alpha (huTRIM5alpha) 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 TRIM5alpha (rhTRIM5alpha) are similarly important for Human Immunodeficiency Type 1 (HIV-) restriction. RESULTS: We found that mutation of SIM1 and SIM2 of rhTRIM5alpha abolished the restriction of HIV-1 virus. Further, knockdown of SUMO-1 in rhTRIM5alpha expressing cells abolished restriction of HIV-1. These results may be due, in part, to the ability of SUMO-1 to stabilize rhTRIM5alpha protein expression, as SUMO-1 knockdown increased rhTRIM5alpha turnover and the mutations in SIM1 and SIM2 led to more rapid degradation than the wild type protein. The NF-kappaB signaling ability of rhTRIM5alpha was also attenuated by SUMO-1 knockdown. Finally, upon inhibition of CRM1-dependent nuclear export with Leptomycin B (LMB), wild type rhTRIM5alpha 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 rhTRIM5alpha 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 TRIM5alpha protein levels and its nuclear localization into specific nuclear bodies.
Journal Title: Retrovirology
Volume: 10
ISSN: 1742-4690; 1742-4690
Publisher: Unknown  
Journal Place: England
Date Published: 2013
Start Page: 10
End Page: 4690-10-10
Language: eng
DOI/URL:

10.1186/1742-4690-10-10

10.1186/1742-4690-10-10
Notes: ID: 13051; GR: R01 AI093258/AI/NIAID NIH HHS/United States; GR: R01 AI093258/AI/NIAID NIH HHS/United States; GR: Howard Hughes Medical Institute/United States; JID: 101216893; OID: NLM: PMC3599732; 2012/09/16 [received]; 2013/01/16 [accepted]; 2013/02/01 [aheadofprint]; epublish