Key Points
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The tripartite motif (TRIM) family is a wide and well conserved family of proteins characterized by a tripartite structure comprising a RING domain, one or two B-boxes and a predicted coiled-coil region. In addition, most TRIM proteins have additional C-terminal domains of various kinds.
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TRIM19, better known as PML (for promyelocytic leukaemia protein) forms nuclear structures referred to as nuclear bodies. Proteins encoded by various and unrelated viruses have been shown to target PML and to cause the disruption of nuclear bodies, suggesting that these structures might represent an antiviral barrier.
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TRIM19 has been proposed to be involved in interferon-mediated antiviral response against several viruses, but its direct implication remains controversial.
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TRIM5α has been recently shown to be responsible for the resistance of primate cells to diverse retrovirus infection. It blocks an early step of retroviral infection prior to reverse transcription. Like its murine cousin, Fv1, TRIM5α restriction is believed to target the capsid protein.
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How TRIM5α blocks an early step of retroviral replication is still unknown. Diverse hypotheses are being explored. TRIM5α could interfere with the disassembly of viral cores, sequester them in a subcellular compartment, induce their degradation during transit across the cytoplasm or prevent some vital interaction between cellular proteins and viral components.
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Although very few TRIM proteins have been individually studied, other members of this family have been reported to interfere with viral replication, such as TRIM1 and TRIM22, suggesting viral interference might be a general characteristic of the whole family.
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The capacity of TRIMs to form high-order molecular-weight structures located in different cellular compartments and their capacity to recruit multiple cellular proteins would allow them to efficiently counteract cellular infection by a wide array of viruses. These observations lead us to discuss the possibility that the TRIM family might represent a new class of antiviral proteins involved in innate immunity.
Abstract
Members of the tripartite motif (TRIM) protein family are involved in various cellular processes, including cell proliferation, differentiation, development, oncogenesis and apoptosis. Some TRIM proteins display antiviral properties, targeting retroviruses in particular. The potential activity of TRIM19, better known as promyelocytic leukaemia protein, against several viruses has been well documented and, recently, TRIM5α has been identified as the factor responsible for the previously described Lv1 and Ref1 antiretroviral activities. There is also evidence indicating that other TRIM proteins can influence viral replication. These findings are reviewed here, and the possibility that TRIMs represent a new and widespread class of antiviral proteins involved in innate immunity is also considered.
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References
Isaacs, A. & Burke, D. C. Mode of action of interferon. Nature 182, 1073–1074 (1958).
Medzhitov, R., Preston-Hurlburt, P. & Janeway, C. A. Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394–397 (1997).
Goff, S. P. Retrovirus restriction factors. Mol. Cell 16, 849–859 (2004).
Harris, R. S. & Liddament, M. T. Retroviral restriction by APOBEC proteins. Nature Rev. Immunol. 4, 868–877 (2004).
Voinnet, O. Induction and suppression of RNA silencing: insights from viral infections. Nature Rev. Genet. 6, 206–220 (2005).
Gao, G., Guo, X. & Goff, S. P. Inhibition of retroviral RNA production by ZAP, a CCCH-type zinc finger protein. Science 297, 1703–1706 (2002).
Reddy, B. A., Kloc, M. & Etkin, L. The cloning and characterization of a maternally expressed novel zinc finger nuclear phosphoprotein (xnf7) in Xenopus laevis. Dev. Biol. 148, 107–116 (1991). Cloning of the first TRIM.
Reymond, A. et al. The tripartite motif family identifies cell compartments. EMBO J. 20, 2140–2151 (2001). Pioneering characterization of the TRIM family.
Ota, T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature Genet. 36, 40–45 (2004).
Strausberg, R. L. et al. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc. Natl Acad. Sci. USA 99, 16899–16903 (2002).
Miyamoto, K. et al. RING finger, B-box, and coiled-coil (RBCC) protein expression in branchial epithelial cells of Japanese eel, Anguilla japonica. Eur. J. Biochem. 269, 6152–6161 (2002).
C. elegans Sequencing Consortium. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282, 2012–2018 (1998).
Saurin, A. J., Borden, K. L., Boddy, M. N. & Freemont, P. S. Does this have a familiar RING? Trends Biochem. Sci. 21, 208–214 (1996).
Lovering, R. et al. Identification and preliminary characterization of a protein motif related to the zinc finger. Proc. Natl Acad. Sci. USA 90, 2112–2116 (1993). Identification of the first RING domain.
Borden, K. L. RING domains: master builders of molecular scaffolds? J. Mol. Biol. 295, 1103–1112 (2000).
Freemont, P. S. RING for destruction? Curr. Biol. 10, R84–R87 (2000).
Joazeiro, C. A. & Weissman, A. M. RING finger proteins: mediators of ubiquitin ligase activity. Cell 102, 549–552 (2000).
Xu, L. et al. BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5δ. Exp. Cell Res. 288, 84–93 (2003).
Trockenbacher, A. et al. MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation. Nature Genet. 29, 287–294 (2001).
Urano, T. et al. Efp targets 14-3-3σ for proteolysis and promotes breast tumour growth. Nature 417, 871–875 (2002).
Horn, E. J. et al. RING protein Trim32 associated with skin carcinogenesis has anti-apoptotic and E3-ubiquitin ligase properties. Carcinogenesis 25, 157–167 (2004).
Vichi, A., Payne, D. M., Pacheco-Rodriguez, G., Moss, J. & Vaughan, M. E3 ubiquitin ligase activity of the trifunctional ARD1 (ADP-ribosylation factor domain protein 1). Proc. Natl Acad. Sci. USA 102, 1945–1950 (2005).
Reddy, B. A., Etkin, L. D. & Freemont, P. S. A novel zinc finger coiled-coil domain in a family of nuclear proteins. Trends Biochem. Sci. 17, 344–345 (1992). Provides the first characterization of a coiled-coil domain.
Borden, K. L. et al. In vivo and in vitro characterization of the B1 and B2 zinc-binding domains from the acute promyelocytic leukemia protooncoprotein PML. Proc. Natl Acad. Sci. USA 93, 1601–1606 (1996).
Cao, T., Borden, K. L., Freemont, P. S. & Etkin, L. D. Involvement of the rfp tripartite motif in protein—protein interactions and subcellular distribution. J. Cell Sci. 110, 1563–1571 (1997).
Borden, K. L. et al. The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBO J. 14, 1532–1541 (1995).
Peng, H. et al. Reconstitution of the KRAB-KAP-1 repressor complex: a model system for defining the molecular anatomy of RING-B box-coiled-coil domain-mediated protein—protein interactions. J. Mol. Biol. 295, 1139–1162 (2000).
Ponting, C., Schultz, J. & Bork, P. SPRY domains in ryanodine receptors (Ca2+-release channels). Trends Biochem. Sci. 22, 193–194 (1997). The first report to identify SPRY domains.
Henry, J., Mather, I. H., McDermott, M. F. & Pontarotti, P. B30.2-like domain proteins: update and new insights into a rapidly expanding family of proteins. Mol. Biol. Evol. 15, 1696–1705 (1998).
Vernet, C. et al. Evolutionary study of multigenic families mapping close to the human MHC class I region. J. Mol. Evol. 37, 600–612 (1993).
Hilton, D. J. et al. Twenty proteins containing a C-terminal SOCS box form five structural classes. Proc. Natl Acad. Sci. USA 95, 114–119 (1998).
Aasland, R., Gibson, T. J. & Stewart, A. F. The PHD finger: implications for chromatin-mediated transcriptional regulation. Trends Biochem. Sci. 20, 56–59 (1995).
Le Douarin, B. et al. A possible involvement of TIF1 α and TIF1 β in the epigenetic control of transcription by nuclear receptors. EMBO J. 15, 6701–6715 (1996).
Venturini, L. et al. TIF1γ, a novel member of the transcriptional intermediary factor 1 family. Oncogene 18, 1209–1217 (1999).
The French FMF Consortium. A candidate gene for familial Mediterranean fever. Nature Genet. 17, 25–31 (1997).
Quaderi, N. A. et al. Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22. Nature Genet. 17, 285–291 (1997).
Frosk, P. et al. Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene. Am. J. Hum. Genet. 70, 663–672 (2002).
Avela, K. et al. Gene encoding a new RING-B-box-coiled-coil protein is mutated in mulibrey nanism. Nature Genet. 25, 298–301 (2000).
de The, H. et al. The PML-RARα fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell 66, 675–684 (1991).
Kakizuka, A. et al. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RARα with a novel putative transcription factor, PML. Cell 66, 663–674 (1991).
Goddard, A. D., Borrow, J., Freemont, P. S. & Solomon, E. Characterization of a zinc finger gene disrupted by the t(15;17) in acute promyelocytic leukemia. Science 254, 1371–1374 (1991). References 39–41 report the identification of PML as a PML–RARα fusion protein.
Takahashi, M., Inaguma, Y., Hiai, H. & Hirose, F. Developmentally regulated expression of a human 'finger'-containing gene encoded by the 5′ half of the ret transforming gene. Mol. Cell Biol. 8, 1853–1856 (1988).
Le Douarin, B. et al. The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18. EMBO J. 14, 2020–2033 (1995).
Stremlau, M. et al. The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys. Nature 427, 848–853 (2004). Direct demonstration of the anti-HIV activity of simian TRIM5α.
Hatziioannou, T., Perez-Caballero, D., Yang, A., Cowan, S. & Bieniasz, P. D. Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5α. Proc. Natl Acad. Sci. USA 101, 10774–10779 (2004).
Keckesova, Z., Ylinen, L. M. & Towers, G. J. The human and African green monkey TRIM5α genes encode Ref1 and Lv1 retroviral restriction factor activities. Proc. Natl Acad. Sci. USA 101, 10780–10785 (2004).
Perron, M. J. et al. TRIM5α mediates the postentry block to N-tropic murine leukemia viruses in human cells. Proc. Natl Acad. Sci. USA 101, 11827–11832 (2004).
Yap, M. W., Nisole, S., Lynch, C. & Stoye, J. P. Trim5α protein restricts both HIV-1 and murine leukemia virus. Proc. Natl Acad. Sci. USA 101, 10786–10791 (2004). References 45–48 identify TRIM5α as the factor responsible for Ref1 and Lv1 restriction activities.
Tissot, C. & Mechti, N. Molecular cloning of a new interferon-induced factor that represses human immunodeficiency virus type 1 long terminal repeat expression. J. Biol. Chem. 270, 14891–14898 (1995).
Hofmann, T. G. & Will, H. Body language: the function of PML nuclear bodies in apoptosis regulation. Cell Death Differ. 10, 1290–1299 (2003).
Kentsis, A. et al. The RING domains of the promyelocytic leukemia protein PML and the arenaviral protein Z repress translation by directly inhibiting translation initiation factor eIF4E. J. Mol. Biol. 312, 609–623 (2001).
Pearson, M. et al. PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature 406, 207–210 (2000).
Wang, Z. G. et al. Role of PML in cell growth and the retinoic acid pathway. Science 279, 1547–1551 (1998).
Lin, H. K., Bergmann, S. & Pandolfi, P. P. Cytoplasmic PML function in TGF-β signalling. Nature 431, 205–211 (2004).
Koken, M. H. et al. The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible fashion. EMBO J. 13, 1073–1083 (1994).
Muller, S., Matunis, M. J. & Dejean, A. Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus. EMBO J. 17, 61–70 (1998). First evidence for the involvement of SUMO in the control of PML localization.
Ishov, A. M. et al. PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1. J. Cell Biol. 147, 221–234 (1999).
Sternsdorf, T., Jensen, K. & Will, H. Evidence for covalent modification of the nuclear dot-associated proteins PML and Sp100 by PIC1/SUMO-1. J. Cell Biol. 139, 1621–1634 (1997).
Dyck, J. A. et al. A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell 76, 333–343 (1994).
Weis, K. et al. Retinoic acid regulates aberrant nuclear localization of PML–RARα in acute promyelocytic leukemia cells. Cell 76, 345–356 (1994).
Zhu, J., Chen, Z., Lallemand-Breitenbach, V. & de The, H. How acute promyelocytic leukaemia revived arsenic. Nature Rev. Cancer 2, 705–713 (2002).
Zhu, J. et al. Arsenic-induced PML targeting onto nuclear bodies: implications for the treatment of acute promyelocytic leukemia. Proc. Natl Acad. Sci. USA 94, 3978–3983 (1997).
Lallemand-Breitenbach, V. et al. Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor α degradation. J. Exp. Med. 193, 1361–1371 (2001).
Boutell, C., Orr, A. & Everett, R. D. PML residue lysine 160 is required for the degradation of PML induced by herpes simplex virus type 1 regulatory protein ICP0. J. Virol. 77, 8686–8694 (2003).
Borden, K. L. Pondering the promyelocytic leukemia protein (PML) puzzle: possible functions for PML nuclear bodies. Mol. Cell Biol. 22, 5259–5269 (2002).
Stadler, M. et al. Transcriptional induction of the PML growth suppressor gene by interferons is mediated through an ISRE and a GAS element. Oncogene 11, 2565–2573 (1995).
Chelbi-Alix, M. K. et al. Induction of the PML protein by interferons in normal and APL cells. Leukemia 9, 2027–2033 (1995).
Lavau, C. et al. The acute promyelocytic leukaemia-associated PML gene is induced by interferon. Oncogene 11, 871–876 (1995).
Katze, M. G., He, Y. & Gale, M. Jr. Viruses and interferon: a fight for supremacy. Nature Rev. Immunol. 2, 675–687 (2002).
Chelbi-Alix, M. K., Quignon, F., Pelicano, L., Koken, M. H. & de The, H. Resistance to virus infection conferred by the interferon-induced promyelocytic leukemia protein. J. Virol. 72, 1043–1051 (1998). First evidence for an antiviral activity of PML.
Asper, M. et al. Inhibition of different Lassa virus strains by α and γ interferons and comparison with a less pathogenic arenavirus. J. Virol. 78, 3162–3169 (2004).
Turelli, P. et al. Cytoplasmic recruitment of INI1 and PML on incoming HIV preintegration complexes: interference with early steps of viral replication. Mol. Cell 7, 1245–1254 (2001). Important but controversial paper describing the inhibition of HIV by PML.
Bell, P., Montaner, L. J. & Maul, G. G. Accumulation and intranuclear distribution of unintegrated human immunodeficiency virus type 1 DNA. J. Virol. 75, 7683–7691 (2001).
Berthoux, L. et al. As2O3 enhances retroviral reverse transcription and counteracts Ref1 antiviral activity. J. Virol. 77, 3167–3180 (2003).
Regad, T. et al. PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator. EMBO J. 20, 3495–3505 (2001).
Meiering, C. D. & Linial, M. L. The promyelocytic leukemia protein does not mediate foamy virus latency in vitro. J. Virol. 77, 2207–2213 (2003).
Borden, K. L., Campbell Dwyer, E. J. & Salvato, M. S. An arenavirus RING (zinc-binding) protein binds the oncoprotein promyelocyte leukemia protein (PML) and relocates PML nuclear bodies to the cytoplasm. J. Virol. 72, 758–766 (1998).
Blondel, D. et al. Rabies virus P and small P products interact directly with PML and reorganize PML nuclear bodies. Oncogene 21, 7957–7970 (2002).
Maul, G. G., Guldner, H. H. & Spivack, J. G. Modification of discrete nuclear domains induced by herpes simplex virus type 1 immediate early gene 1 product (ICP0). J. Gen. Virol. 74, 2679–2690 (1993). Pioneering paper reporting the disruption of NBs by a viral protein.
Everett, R. D. & Maul, G. G. HSV-1 IE protein Vmw110 causes redistribution of PML. EMBO J. 13, 5062–5069 (1994).
Chelbi-Alix, M. K. & de The, H. Herpes virus induced proteasome-dependent degradation of the nuclear bodies-associated PML and Sp100 proteins. Oncogene 18, 935–941 (1999).
Muller, S. & Dejean, A. Viral immediate-early proteins abrogate the modification by SUMO-1 of PML and Sp100 proteins, correlating with nuclear body disruption. J. Virol. 73, 5137–5143 (1999).
Boutell, C., Sadis, S. & Everett, R. D. Herpes simplex virus type 1 immediate-early protein ICP0 and is isolated RING finger domain act as ubiquitin E3 ligases in vitro. J. Virol. 76, 841–850 (2002).
Hagglund, R. & Roizman, B. Characterization of the novel E3 ubiquitin ligase encoded in exon 3 of herpes simplex virus-1-infected cell protein 0. Proc. Natl Acad. Sci. USA 99, 7889–7894 (2002).
Boutell, C. & Everett, R. D. The herpes simplex virus type 1 (HSV-1) regulatory protein ICP0 interacts with and ubiquitinates p53. J. Biol. Chem. 278, 36596–36602 (2003).
Gu, H. & Roizman, B. The degradation of promyelocytic leukemia and Sp100 proteins by herpes simplex virus 1 is mediated by the ubiquitin-conjugating enzyme UbcH5a. Proc. Natl Acad. Sci. USA 100, 8963–8968 (2003).
Lopez, P., Jacob, R. J. & Roizman, B. Overexpression of promyelocytic leukemia protein precludes the dispersal of ND10 structures and has no effect on accumulation of infectious herpes simplex virus 1 or its proteins. J. Virol. 76, 9355–9367 (2002).
Chee, A. V., Lopez, P., Pandolfi, P. P. & Roizman, B. Promyelocytic leukemia protein mediates interferon-based anti-herpes simplex virus 1 effects. J. Virol. 77, 7101–7105 (2003).
Parkinson, J. & Everett, R. D. αherpesvirus proteins related to herpes simplex virus type 1 ICP0 affect cellular structures and proteins. J. Virol. 74, 10006–10017 (2000).
Lilly, F. Fv-2: Identification and location of a second gene governing the spleen focus response to Friend leukemia virus in mice. J. Natl Cancer Inst. 45, 163–169 (1970).
Hartley, J. W., Rowe, W. P. & Huebner, R. J. Host-range restrictions of murine leukemia viruses in mouse embryo cell cultures. J. Virol. 5, 221–225 (1970).
DesGroseillers, L. & Jolicoeur, P. Physical mapping of the Fv-1 tropism host range determinant of BALB/c murine leukemia viruses. J. Virol. 48, 685–696 (1983).
Kozak, C. A. & Chakraborti, A. Single amino acid changes in the murine leukemia virus capsid protein gene define the target of Fv1 resistance. Virology 225, 300–305 (1996).
Stoye, J. P. Fv1, the mouse retrovirus resistance gene. Rev. Sci. Tech. 17, 269–277 (1998).
Best, S., Le Tissier, P., Towers, G. & Stoye, J. P. Positional cloning of the mouse retrovirus restriction gene Fv1. Nature 382, 826–829 (1996). Cloning of Fv1, the prototype of restriction factors.
Cordonnier, A., Casella, J. -F. & Heidmann, T. Isolation of novel human endogenous retrovirus-like elements with foamy virus-related pol sequence. J. Virol. 69, 5890–5897 (1995).
Goff, S. P. Operating under a Gag order: a block against incoming virus by the Fv1 gene. Cell 86, 691–693 (1996).
Benit, L. et al. Cloning of a new murine endogenous retrovirus, MuERV-L, with strong similarity to the human HERV-L element and with a gag coding sequence closely related to the Fv1 restriction gene. J. Virol. 71, 5652–5657 (1997).
Towers, G. et al. A conserved mechanism of retrovirus restriction in mammals. Proc. Natl Acad. Sci. USA 97, 12295–12299 (2000). First evidence for the existence of Fv1-like factors in non-murine cells.
Besnier, C. et al. Characterization of murine leukemia virus restriction in mammals. J. Virol. 77, 13403–13406 (2003).
Hofmann, W. et al. Species-specific, postentry barriers to primate immunodeficiency virus infection. J. Virol. 73, 10020–10028 (1999).
Besnier, C., Takeuchi, Y. & Towers, G. Restriction of lentivirus in monkeys. Proc. Natl Acad. Sci. USA 99, 11920–11925 (2002).
Cowan, S. et al. Cellular inhibitors with Fv1-like activity restrict human and simian immunodeficiency virus tropism. Proc. Natl Acad. Sci. USA 99, 11914–11919 (2002).
Munk, C., Brandt, S. M., Lucero, G. & Landau, N. R. A dominant block to HIV-1 replication at reverse transcription in simian cells. Proc. Natl Acad. Sci. USA 99, 13843–13848 (2002).
Yap, M. W., Nisole, S. & Stoye, J. P. A single amino acid change in the SPRY domain of human Trim5α leads to HIV-1 restriction. Curr. Biol. 15, 73–78 (2005). A rigorous mapping of restriction determinants within TRIM5α.
Stremlau, M., Perron, M., Welikala, S. & Sodroski, J. Species-specific variation in the B30.2(SPRY) domain of TRIM5α determines the potency of human immunodeficiency virus restriction. J. Virol. 79, 3139–3145 (2005).
Haran-Ghera, N., Peled, A., Brightman, B. K. & Fan, H. Lymphomagenesis in AKR. Fv-1b congenic mice. Cancer Res. 53, 3433–3438 (1993).
Sawyer, S. L., Wu, L. I., Emerman, M. & Malik, H. S. Positive selection of primate TRIM5α identifies a critical species-specific retroviral restriction domain. Proc. Natl Acad. Sci. USA 102, 2832–2837 (2005).
Song, B. et al. The B30.2(SPRY) domain of the retroviral restriction factor TRIM5α exhibits lineage-specific length and sequence variation in primates. J. Virol. 79, 6111–6121 (2005).
Jolicoeur, P. The Fv-1 gene of the mouse and its control of murine leukemia virus replication. Curr. Top. Microbiol. Immunol. 86, 67–122 (1979).
Duran-Troise, G., Bassin, R. H., Rein, A. & Gerwin, B. I. Loss of Fv-1 restriction in Balb/3T3 cells following infection with a single N tropic murine leukemia particle. Cell 10, 479–488 (1977).
Yap, M. W. & Stoye, J. P. Intracellular localisation of Fv1. Virology 307, 76–89 (2003).
Nisole, S., Lynch, C., Stoye, J. P. & Yap, M. W. A Trim5-cyclophilin A fusion protein found in owl monkey kidney cells can restrict HIV-1. Proc. Natl Acad. Sci. USA 101, 13324–13328 (2004).
Sayah, D. M., Sokolskaja, E., Berthoux, L. & Luban, J. Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1. Nature 430, 569–573 (2004).
Luban, J., Bossolt, K. L., Franke, E. K., Kalpana, G. V. & Goff, S. P. Human immunodeficiency virus type 1 Gag protein binds to cyclophilins A and B. Cell 73, 1067–1078 (1993).
Gamble, T. R. et al. Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid. Cell 87, 1285–1294 (1996).
Towers, G. J. et al. Cyclophilin A modulates the sensitivity of HIV-1 to host restriction factors. Nature Med. 9, 1138–1143 (2003).
Forshey, B. M., von Schwedler, U., Sundquist, W. I. & Aiken, S. C. Formation of a human immunodeficiency virus type 1 core of optimal stability is crucial for viral replication. J. Virol. 76, 5667–5677 (2002).
Dodding, M. P., Bock, M., Yap, M. W. & Stoye, J. P. Capsid processing requirements for abrogation of fv1 and ref1 restriction. J. Virol. 79, 10571–10577 (2005).
Mortuza, G. B. et al. High-resolution structure of a retroviral capsid hexameric amino-terminal domain. Nature 431, 481–485 (2004).
Berthoux, L., Sebastian, S., Sokolskaja, E. & Luban, J. Lv1 inhibition of human immunodeficiency virus type 1 is counteracted by factors that stimulate synthesis or nuclear translocation of viral cDNA. J. Virol. 78, 11739–11750 (2004).
Nisole, S. & Saib, A. Early steps of retrovirus replicative cycle. Retrovirology 1, 9 (2004).
Fridell, R. A., Harding, L. S., Bogerd, H. P. & Cullen, B. R. Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins. Virology 209, 347–357 (1995).
Geiss, G. K. et al. Cellular transcriptional profiling in influenza A virus-infected lung epithelial cells: the role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza. Proc. Natl Acad. Sci. USA 99, 10736–10741 (2002).
Wang, Y. et al. TRIM45, a novel human RBCC/TRIM protein, inhibits transcriptional activities of ElK-1 and AP-1. Biochem. Biophys. Res. Commun. 323, 9–16 (2004).
Bjorndal, A. S., Szekely, L. & Elgh, F. Ebola virus infection inversely correlates with the overall expression levels of promyelocytic leukaemia (PML) protein in cultured cells. BMC Microbiol. 3, 6 (2003).
Bonilla, W. V. et al. Effects of promyelocytic leukemia protein on virus–host balance. J. Virol. 76, 3810–3818 (2002).
Djavani, M. et al. Role of the promyelocytic leukemia protein PML in the interferon sensitivity of lymphocytic choriomeningitis virus. J. Virol. 75, 6204–6208 (2001).
Acknowledgements
We thank L. Burleigh and V. Lallemand-Breitenbach for critical review of the manuscript. S.N. is supported by the Fondation pour la Recherche Médicale. This work was supported by the Medical Research Council UK and the Agence Nationale de Recherches sur le SIDA.
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Glossary
- UBIQUITIN E3 LIGASE
-
Ubiquitination requires three enzymes: a ubiquitin-activating (E1) enzyme, a ubiquitin-conjugating (E2) enzyme and a ubiquitin-protein ligase (E3) enzyme. Two of the main families of E3s are the HECT-domain-containing enzymes (for example, NEDD4) and RING-domain-containing enzymes (for example, Cbl).
- EXON SHUFFLING
-
The process of non-homologous recombination of exons from different genes.
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Nisole, S., Stoye, J. & Saïb, A. TRIM family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol 3, 799–808 (2005). https://doi.org/10.1038/nrmicro1248
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