Contribution of SUMO-interacting Motifs and SUMOylation to the Antiretroviral Properties of TRIM5α

Overview

Journal Virology

Specialty Microbiology

Date 2012 Oct 23

PMID 23084420

Citations 10

Authors

Alberto Brandariz-Nunez

Amanda Roa

Jose Carlos Valle-Casuso

Nikolaos Biris

Dmitri Ivanov

Felipe Diaz-Griffero

Affiliations

Soon will be listed here.

Abstract

Recent findings suggested that the SUMO-interacting motifs (SIMs) present in the human TRIM5α (TRIM5α(hu)) protein play an important role in the ability of TRIM5α(hu) to restrict N-MLV. Here we explored the role of SIMs in the ability of rhesus TRIM5α (TRIM5α(rh)) to restrict HIV-1, and found that TRIM5α(rh) SIM mutants IL376KK (SIM1mut) and VI405KK (SIM2mut) completely lost their ability to block HIV-1 infection. Interestingly, these mutants also lost the recently described property of TRIM5α(rh) to shuttle into the nucleus. Analysis of these variants revealed that they are unable to interact with the HIV-1 core, which might explain the reason that these variants are not active against HIV-1. Furthermore, NMR titration experiments to assay the binding between the PRYSPRY domain of TRIM5α(rh) and the small ubiquitin-like modifier 1(SUMO-1) revealed no interaction. In addition, we examined the role of SUMOylation in restriction, and find out that inhibition of SUMOylation by the adenoviral protein Gam1 did not alter the retroviral restriction ability of TRIM5α. Overall, our results do not support a role for SIMs or SUMOylation in the antiviral properties of TRIM5α.

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References

Yueh A, Leung J, Bhattacharyya S, Perrone L, de Los Santos K, Pu S . Interaction of moloney murine leukemia virus capsid with Ubc9 and PIASy mediates SUMO-1 addition required early in infection. J Virol. 2005; 80(1):342-52. PMC: 1317516. DOI: 10.1128/JVI.80.1.342-352.2006. View

Kim J, Tipper C, Sodroski J . Role of TRIM5α RING domain E3 ubiquitin ligase activity in capsid disassembly, reverse transcription blockade, and restriction of simian immunodeficiency virus. J Virol. 2011; 85(16):8116-32. PMC: 3147946. DOI: 10.1128/JVI.00341-11. View

Ohkura S, Yap M, Sheldon T, Stoye J . All three variable regions of the TRIM5alpha B30.2 domain can contribute to the specificity of retrovirus restriction. J Virol. 2006; 80(17):8554-65. PMC: 1563890. DOI: 10.1128/JVI.00688-06. View

Kuersten S, Ohno M, Mattaj I . Nucleocytoplasmic transport: Ran, beta and beyond. Trends Cell Biol. 2001; 11(12):497-503. DOI: 10.1016/s0962-8924(01)02144-4. View

Langelier C, Sandrin V, Eckert D, Christensen D, Chandrasekaran V, Alam S . Biochemical characterization of a recombinant TRIM5alpha protein that restricts human immunodeficiency virus type 1 replication. J Virol. 2008; 82(23):11682-94. PMC: 2583683. DOI: 10.1128/JVI.01562-08. View

Nakayama E, Miyoshi H, Nagai Y, Shioda T . A specific region of 37 amino acid residues in the SPRY (B30.2) domain of African green monkey TRIM5alpha determines species-specific restriction of simian immunodeficiency virus SIVmac infection. J Virol. 2005; 79(14):8870-7. PMC: 1168783. DOI: 10.1128/JVI.79.14.8870-8877.2005. View

Sebastian S, Luban J . TRIM5alpha selectively binds a restriction-sensitive retroviral capsid. Retrovirology. 2005; 2:40. PMC: 1166576. DOI: 10.1186/1742-4690-2-40. View

Colombo R, Boggio R, Seiser C, Draetta G, Chiocca S . The adenovirus protein Gam1 interferes with sumoylation of histone deacetylase 1. EMBO Rep. 2002; 3(11):1062-8. PMC: 1307602. DOI: 10.1093/embo-reports/kvf213. View

Boggio R, Colombo R, Hay R, Draetta G, Chiocca S . A mechanism for inhibiting the SUMO pathway. Mol Cell. 2004; 16(4):549-61. DOI: 10.1016/j.molcel.2004.11.007. View

10.

Diaz-Griffero F, Vandegraaff N, Li Y, McGee-Estrada K, Stremlau M, Welikala S . Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1. Virology. 2006; 351(2):404-19. DOI: 10.1016/j.virol.2006.03.023. View

11.

Yee J, Friedmann T, Burns J . Generation of high-titer pseudotyped retroviral vectors with very broad host range. Methods Cell Biol. 1994; 43 Pt A:99-112. DOI: 10.1016/s0091-679x(08)60600-7. View

12.

Boggio R, Passafaro A, Chiocca S . Targeting SUMO E1 to ubiquitin ligases: a viral strategy to counteract sumoylation. J Biol Chem. 2007; 282(21):15376-82. DOI: 10.1074/jbc.M700889200. View

13.

Ganser-Pornillos B, Chandrasekaran V, Pornillos O, Sodroski J, Sundquist W, Yeager M . Hexagonal assembly of a restricting TRIM5alpha protein. Proc Natl Acad Sci U S A. 2010; 108(2):534-9. PMC: 3021009. DOI: 10.1073/pnas.1013426108. View

14.

Johnson E . Protein modification by SUMO. Annu Rev Biochem. 2004; 73:355-82. DOI: 10.1146/annurev.biochem.73.011303.074118. View

15.

Sayah D, Sokolskaja E, Berthoux L, Luban J . Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1. Nature. 2004; 430(6999):569-73. DOI: 10.1038/nature02777. View

16.

Kirmaier A, Wu F, Newman R, Hall L, Morgan J, OConnor S . TRIM5 suppresses cross-species transmission of a primate immunodeficiency virus and selects for emergence of resistant variants in the new species. PLoS Biol. 2010; 8(8). PMC: 2927514. DOI: 10.1371/journal.pbio.1000462. View

17.

Diaz-Griffero F, Qin X, Hayashi F, Kigawa T, Finzi A, Sarnak Z . A B-box 2 surface patch important for TRIM5alpha self-association, capsid binding avidity, and retrovirus restriction. J Virol. 2009; 83(20):10737-51. PMC: 2753111. DOI: 10.1128/JVI.01307-09. View

18.

Diaz-Griffero F, Hoschander S, Brojatsch J . Endocytosis is a critical step in entry of subgroup B avian leukosis viruses. J Virol. 2002; 76(24):12866-76. PMC: 136682. DOI: 10.1128/jvi.76.24.12866-12876.2002. View

19.

Diaz-Griffero F, Gallo D, Hope T, Sodroski J . Trafficking of some old world primate TRIM5α proteins through the nucleus. Retrovirology. 2011; 8:38. PMC: 3120760. DOI: 10.1186/1742-4690-8-38. View

20.

Diaz-Griffero F, Kar A, Lee M, Stremlau M, Poeschla E, Sodroski J . Comparative requirements for the restriction of retrovirus infection by TRIM5alpha and TRIMCyp. Virology. 2007; 369(2):400-10. PMC: 2153441. DOI: 10.1016/j.virol.2007.08.032. View