Trafficking of some old world primate TRIM5α proteins through the nucleus

Retrovirology

Joseph Sodroski³  Thomas J Hope²  Daniel E Gallo²  Felipe Diaz-Griffero¹ 

[1] Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA;Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA;Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA

关键词: leptomycin B;    retrovirus;    intracellular localization;    Restriction factor;   

Others  :  1209440
DOI  :  10.1186/1742-4690-8-38

 received in 2011-02-01, accepted in 2011-05-15,  发布年份 2011

【 摘 要 】

Background

TRIM5α and TRIMCyp are cytoplasmic proteins that bind incoming retroviral capsids and mediate early blocks to viral infection. TRIM5 proteins form cytoplasmic bodies, which are highly dynamic structures. So far, TRIM5 proteins have been found only in the cytoplasm of cells. Interestingly, other proteins from the TRIM family localize to the nucleus. Therefore, we tested the possibility that TRIM5 proteins traffic to the nucleus and the impact of this trafficking on retroviral restriction.

Results

Here we report that the TRIM5α proteins of two Old World primates, humans and rhesus monkeys, are transported into the nucleus and are shuttled back to the cytoplasm by a leptomycin B-sensitive mechanism. In leptomycin B-treated cells, these TRIM5α proteins formed nuclear bodies that also contained TRIM19 (PML). Deletion of the amino terminus, including the linker 1 (L1) region, resulted in TRIM5α proteins that accumulated in nuclear bodies. Leptomycin B treatment of TRIM5α-expressing target cells only minimally affected the restriction of retrovirus infection.

Conclusions

We discovered the ability of human and rhesus TRIM5α to shuttle into and out of the nucleus. This novel trafficking ability of TRIM5α proteins could be important for an as-yet-unknown function of TRIM5α.

【 授权许可】

   
2011 Diaz-Griffero et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, et al.: The tripartite motif family identifies cell compartments. Embo J 2001, 20:2140-2151.
• [2]Nisole S, Stoye JP, Saib A: TRIM family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol 2005, 3:799-808.
• [3]Stremlau M, Owens CM, Perron MJ, Kiessling M, Autissier P, Sodroski J: The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys. Nature 2004, 427:848-853.
• [4]Hatziioannou T, Perez-Caballero D, Yang A, Cowan S, Bieniasz PD: Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5alpha. Proc Natl Acad Sci USA 2004, 101:10774-10779.
• [5]Keckesova Z, Ylinen LM, Towers GJ: The human and African green monkey TRIM5alpha genes encode Ref1 and Lv1 retroviral restriction factor activities. Proc Natl Acad Sci USA 2004, 101:10780-10785.
• [6]Perron MJ, Stremlau M, Song B, Ulm W, Mulligan RC, Sodroski J: TRIM5alpha mediates the postentry block to N-tropic murine leukemia viruses in human cells. Proc Natl Acad Sci USA 2004, 101:11827-11832.
• [7]Yap MW, Nisole S, Lynch C, Stoye JP: Trim5alpha protein restricts both HIV-1 and murine leukemia virus. Proc Natl Acad Sci USA 2004, 101:10786-10791.
• [8]Song B, Javanbakht H, Perron M, Park DH, Stremlau M, Sodroski J: Retrovirus restriction by TRIM5alpha variants from Old World and New World primates. J Virol 2005, 79:3930-3937.
• [9]Nisole S, Lynch C, Stoye JP, Yap MW: A Trim5-cyclophilin A fusion protein found in owl monkey kidney cells can restrict HIV-1. Proc Natl Acad Sci USA 2004, 101:13324-13328.
• [10]Sayah DM, Sokolskaja E, Berthoux L, Luban J: Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1. Nature 2004, 430:569-573.
• [11]Song B, Gold B, O'Huigin C, Javanbakht H, Li X, Stremlau M, Winkler C, Dean M, Sodroski J: The B30.2(SPRY) domain of the retroviral restriction factor TRIM5alpha exhibits lineage-specific length and sequence variation in primates. J Virol 2005, 79:6111-6121.
• [12]Kono K, Bozek K, Domingues FS, Shioda T, Nakayama EE: Impact of a single amino acid in the variable region 2 of the Old World monkey TRIM5alpha SPRY (B30.2) domain on anti-human immunodeficiency virus type 2 activity. Virology 2009, 388:160-168.
• [13]Sebastian S, Grutter C, de Castillia CS, Pertel T, Olivari S, Grutter MG, Luban J: An invariant surface patch on the TRIM5alpha PRYSPRY domain is required for retroviral restriction but dispensable for capsid binding. J Virol 2009, 83:3365-3373.
• [14]Sawyer SL, Wu LI, Emerman M, Malik HS: Positive selection of primate TRIM5alpha identifies a critical species-specific retroviral restriction domain. Proc Natl Acad Sci USA 2005, 102:2832-2837.
• [15]Perez-Caballero D, Hatziioannou T, Yang A, Cowan S, Bieniasz PD: Human tripartite motif 5alpha domains responsible for retrovirus restriction activity and specificity. J Virol 2005, 79:8969-8978.
• [16]Ohkura S, Yap MW, Sheldon T, Stoye JP: All three variable regions of the TRIM5alpha B30.2 domain can contribute to the specificity of retrovirus restriction. J Virol 2006, 80:8554-8565.
• [17]Yap MW, Nisole S, Stoye JP: A single amino acid change in the SPRY domain of human Trim5alpha leads to HIV-1 restriction. Curr Biol 2005, 15:73-78.
• [18]Nakayama EE, 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, 79:8870-8877.
• [19]Stremlau M, Perron M, Welikala S, Sodroski J: Species-specific variation in the B30.2(SPRY) domain of TRIM5alpha determines the potency of human immunodeficiency virus restriction. J Virol 2005, 79:3139-3145.
• [20]Kar AK, Diaz-Griffero F, Li Y, Li X, Sodroski J: Biochemical and biophysical characterization of a chimeric TRIM21-TRIM5alpha protein. J Virol 2008, 82:11669-11681.
• [21]Langelier CR, Sandrin V, Eckert DM, Christensen DE, Chandrasekaran V, Alam SL, Aiken C, Olsen JC, Kar AK, Sodroski JG, Sundquist WI: Biochemical characterization of a recombinant TRIM5alpha protein that restricts human immunodeficiency virus type 1 replication. J Virol 2008, 82:11682-11694.
• [22]Sebastian S, Luban J: TRIM5alpha selectively binds a restriction-sensitive retroviral capsid. Retrovirology 2005, 2:40. BioMed Central Full Text
• [23]Stremlau M, Perron M, Lee M, Li Y, Song B, Javanbakht H, Diaz-Griffero F, Anderson DJ, Sundquist WI, Sodroski J: Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor. Proc Natl Acad Sci USA 2006, 103:5514-5519.
• [24]Diaz-Griffero F, Qin XR, Hayashi F, Kigawa T, Finzi A, Sarnak Z, Lienlaf M, Yokoyama S, Sodroski J: A B-box 2 Surface Patch Important for TRIM5{alpha} Self-Association, Capsid-binding Avidity and Retrovirus Restriction. J Virol 2009.
• [25]Li X, Sodroski J: The TRIM5alpha B-box 2 domain promotes cooperative binding to the retroviral capsid by mediating higher-order self-association. J Virol 2008, 82:11495-11502.
• [26]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.
• [27]Campbell EM, Perez O, Anderson JL, Hope TJ: Visualization of a proteasome-independent intermediate during restriction of HIV-1 by rhesus TRIM5alpha. J Cell Biol 2008, 180:549-561.
• [28]Diaz-Griffero F, Kar A, Perron M, Xiang SH, Javanbakht H, Li X, Sodroski J: Modulation of Retroviral Restriction and Proteasome Inhibitor-resistant Turnover by Changes in the TRIM5{alpha} B-box 2 Domain. J Virol 2007.
• [29]Diaz-Griffero F, Perron M, McGee-Estrada K, Hanna R, Maillard PV, Trono D, Sodroski J: A human TRIM5alpha B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus. Virology 2008.
• [30]Perron MJ, Stremlau M, Lee M, Javanbakht H, Song B, Sodroski J: The human TRIM5alpha restriction factor mediates accelerated uncoating of the N-tropic murine leukemia virus capsid. J Virol 2007, 81:2138-2148.
• [31]Everett RD: DNA viruses and viral proteins that interact with PML nuclear bodies. Oncogene 2001, 20:7266-7273.
• [32]Negorev D, Maul GG: Cellular proteins localized at and interacting within ND10/PML nuclear bodies/PODs suggest functions of a nuclear depot. Oncogene 2001, 20:7234-7242.
• [33]Maul GG: Nuclear domain 10, the site of DNA virus transcription and replication. Bioessays 1998, 20:660-667.
• [34]Everett RD, Maul GG: HSV-1 IE protein Vmw110 causes redistribution of PML. Embo J 1994, 13:5062-5069.
• [35]Bjorndal AS, Szekely L, Elgh F: Ebola virus infection inversely correlates with the overall expression levels of promyelocytic leukaemia (PML) protein in cultured cells. BMC Microbiol 2003, 3:6. BioMed Central Full Text
• [36]Bonilla WV, Pinschewer DD, Klenerman P, Rousson V, Gaboli M, Pandolfi PP, Zinkernagel RM, Salvato MS, Hengartner H: Effects of promyelocytic leukemia protein on virus-host balance. J Virol 2002, 76:3810-3818.
• [37]Djavani M, Rodas J, Lukashevich IS, Horejsh D, Pandolfi PP, Borden KL, Salvato MS: Role of the promyelocytic leukemia protein PML in the interferon sensitivity of lymphocytic choriomeningitis virus. J Virol 2001, 75:6204-6208.
• [38]Tareen SU, Emerman M: Human Trim5alpha has additional activities that are uncoupled from retroviral capsid recognition. Virology 2011, 409:113-120.
• [39]Kuroishi A, Bozek K, Shioda T, Nakayama EE: A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Retrovirology 2010, 7:58. BioMed Central Full Text
• [40]Nakayama EE, Shioda T: Anti-retroviral activity of TRIM5 alpha. Rev Med Virol 2010, 20:77-92.
• [41]Xu D, Holko M, Sadler AJ, Scott B, Higashiyama S, Berkofsky-Fessler W, McConnell MJ, Pandolfi PP, Licht JD, Williams BR: Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity. Immunity 2009, 30:802-816.
• [42]Carthagena L, Parise MC, Ringeard M, Chelbi-Alix MK, Hazan U, Nisole S: Implication of TRIM alpha and TRIMCyp in interferon-induced anti-retroviral restriction activities. Retrovirology 2008, 5:59. BioMed Central Full Text
• [43]Nishi K, Yoshida M, Fujiwara D, Nishikawa M, Horinouchi S, Beppu T: Leptomycin B targets a regulatory cascade of crm1, a fission yeast nuclear protein, involved in control of higher order chromosome structure and gene expression. J Biol Chem 1994, 269:6320-6324.
• [44]Watanabe M, Fukuda M, Yoshida M, Yanagida M, Nishida E: Involvement of CRM1, a nuclear export receptor, in mRNA export in mammalian cells and fission yeast. Genes Cells 1999, 4:291-297.
• [45]Wolff B, Sanglier JJ, Wang Y: Leptomycin B is an inhibitor of nuclear export: inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA. Chem Biol 1997, 4:139-147.
• [46]Fornerod M, Ohno M, Yoshida M, Mattaj IW: CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 1997, 90:1051-1060.
• [47]Kuersten S, Ohno M, Mattaj IW: Nucleocytoplasmic transport: Ran, beta and beyond. Trends Cell Biol 2001, 11:497-503.
• [48]Kudo N, Wolff B, Sekimoto T, Schreiner EP, Yoneda Y, Yanagida M, Horinouchi S, Yoshida M: Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1. Exp Cell Res 1998, 242:540-547.
• [49]Mohr D, Frey S, Fischer T, Guttler T, Gorlich D: Characterisation of the passive permeability barrier of nuclear pore complexes. EMBO J 2009, 28:2541-2553.
• [50]Stewart M, Baker RP, Bayliss R, Clayton L, Grant RP, Littlewood T, Matsuura Y: Molecular mechanism of translocation through nuclear pore complexes during nuclear protein import. FEBS Lett 2001, 498:145-149.
• [51]Dabauvalle MC, Franke WW: Determination of the intracellular state of soluble macromolecules by gel filtration in vivo in the cytoplasm of amphibian oocytes. J Cell Biol 1986, 102:2006-2014.
• [52]Hiebert SW, Lamb RA: Cell surface expression of glycosylated, nonglycosylated, and truncated forms of a cytoplasmic protein pyruvate kinase. J Cell Biol 1988, 107:865-876.
• [53]Brameier M, Krings A, MacCallum RM: NucPred--predicting nuclear localization of proteins. Bioinformatics 2007, 23:1159-1160.
• [54]Nair R, Rost B: LOC3D: annotate sub-cellular localization for protein structures. Nucleic Acids Res 2003, 31:3337-3340.
• [55]la Cour T, Kiemer L, Molgaard A, Gupta R, Skriver K, Brunak S: Analysis and prediction of leucine-rich nuclear export signals. Protein Eng Des Sel 2004, 17:527-536.
• [56]Campbell EM, Perez O, Melar M, Hope TJ: Labeling HIV-1 virions with two fluorescent proteins allows identification of virions that have productively entered the target cell. Virology 2007, 360:286-293.
• [57]Diaz-Griffero F, Li X, Javanbakht H, Song B, Welikala S, Stremlau M, Sodroski J: Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5. Virology 2006, 349:300-315.
• [58]Song B, Diaz-Griffero F, Park DH, Rogers T, Stremlau M, Sodroski J: TRIM5alpha association with cytoplasmic bodies is not required for antiretroviral activity. Virology 2005, 343:201-211.
• [59]Reszka N, Zhou C, Song B, Sodroski JG, Knipe DM: Simian TRIM5alpha proteins reduce replication of herpes simplex virus. Virology 2010, 398:243-250.
• [60]Diaz-Griffero F, Hoschander SA, Brojatsch J: Endocytosis is a critical step in entry of subgroup B avian leukosis viruses. J Virol 2002, 76:12866-12876.