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APOBEC Family Proteins: Novel Antiviral Innate Immunity

International Journal of Hematology volume 83, pages 213–216 (2006)Cite this article

Abstract

APOBEC3G has been identified as an anti-human immunodeficiency virus type 1 (HIV-1) host factor that belongs to the APOBEC superfamily of cytidine deaminases. It deaminates cytidine to uridine in nascent minus-strand viral DNA, inducing G-to-A hypermutation in the plus-strand DNA of HIV-1.The accumulating evidence demonstrates that APOBEC family proteins also have an antiviral activity against a wide variety of viruses, including not only retroviruses but also other types of viruses, and that each virus seems to have its own strategy for escaping from APOBEC proteins. These results suggest that the APOBEC3 family plays an important role in antiviral host defense as an innate immunity. Recent progress in research on APOBEC family proteins is reviewed.

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References

  1. Simon JH, Gaddis NC, Fouchier RA, Malim MH. Evidence for a newly discovered cellular anti-HIV-1 phenotype. Nat Med. 1998;4:1397–1400.

    Article  CAS  PubMed  Google Scholar 

  2. Sheehy AM, Gaddis NC, Choi JD, Malim MH. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature. 2002;418:646–650.

    Article  CAS  PubMed  Google Scholar 

  3. Jarmuz A, Chester A, Bayliss J, et al. An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22. Genomics. 2002;79:285–296.

    Article  CAS  PubMed  Google Scholar 

  4. Harris RS, Bishop KN, Sheehy AM, et al. DNA deamination mediates innate immunity to retroviral infection. Cell. 2003;113:803–809.

    Article  CAS  PubMed  Google Scholar 

  5. Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D. Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature. 2003;424:99–103.

    Article  CAS  PubMed  Google Scholar 

  6. Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC, Gao L. The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature. 2003;424:94–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shindo K, Takaori-Kondo A, Kobayashi M, Abudu A, Fukunaga K, Uchiyama T. The enzymatic activity of CEM15/Apobec-3G is essential for the regulation of the infectivity of HIV-1 virion but not a sole determinant of its antiviral activity. J Biol Chem. 2003;278:44412–44416.

    Article  CAS  PubMed  Google Scholar 

  8. Sheehy AM, Gaddis NC, Malim MH. The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med. 2003;9:1404–1407.

    Article  CAS  PubMed  Google Scholar 

  9. Marin M, Rose KM, Kozak SL, Kabat D. HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nat Med. 2003;9:1398–1403.

    Article  PubMed  Google Scholar 

  10. Stopak K, de Noronha C, Yonemoto W, Greene WC. HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Mol Cell. 2003;12:591–601.

    Article  CAS  PubMed  Google Scholar 

  11. Bishop KN, Holmes RK, Sheehy AM, Davidson NO, Cho S-J, Malim MH. Cytidine deamination of retroviral DNA by diverse APOBEC proteins. Curr Biol. 2004;14:1392–1396.

    Article  CAS  PubMed  Google Scholar 

  12. Sasada A, Takaori-Kondo A, Shirakawa K, et al. APOBEC3G targets human T-cell leukemia virus type 1. Retrovirology. 2005;2:32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Navarro F, Bollman B, Chen H, et al. Complementary function of the two catalytic domains of APOBEC3G. Virology. 2005;333:374–386.

    Article  CAS  PubMed  Google Scholar 

  14. Kobayashi M, Takaori-Kondo A, Shindo K, Abudu A, Fukunaga K, Uchiyama T. APOBEC3G targets specific virus species. J Virol. 2004;78:8238–8244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lochelt M, Romen F, Bastone P, et al. The antiretroviral activity of APOBEC3 is inhibited by the foamy virus accessory Bet protein. Proc Natl Acad Sci U S A. 2005;102:7982–7987.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Russell RA, Wiegand HL, Moore MD, Schafer A, McClure MO, Cullen BR. Foamy virus Bet proteins function as novel inhibitors of the APOBEC3 family of innate antiretroviral defense factors. J Virol. 2005;79:8724–8731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Turelli P, Mangeat B, Jost S, Vianin S, Trono D. Inhibition of hepatitis B virus replication by APOBEC3G. Science. 2004;303:1829.

    Article  PubMed  Google Scholar 

  18. Suspene R, Guetard D, Henry M, Sommer P, Wain-Hobson S, Vartanian J-P. Extensive editing of both hepatitis B virus DNA strands by APOBEC3 cytidine deaminases in vitro and in vivo. Proc Natl Acad Sci U S A. 2005;102:8321–8326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Esnault C, Heidmann O, Delebecque F, et al. APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses. Nature. 2005;433:430–433.

    Article  CAS  PubMed  Google Scholar 

  20. Schumacher AJ, Nissley DV, Harris RS. APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast. Proc Natl Acad Sci U S A. 2005;102:9854–9859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Dutko JA, Schafer A, Kenny AE, Cullen BR, Curcio MJ. Inhibition of a yeast LTR retrotransposon by human APOBEC3 cytidine deaminases. Curr Biol. 2005;15:661–666.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Teng B, Burant CF, Davidson NO. Molecular cloning of an apolipoprotein B messenger RNA editing protein. Science. 1993;260:1816–1819.

    Article  CAS  PubMed  Google Scholar 

  23. Anant S, Mukhopadhyay D, Sankaranand V, Kennedy S, Henderson JO, Davidson NO. ARCD-1, an apobec-1-related cytidine deaminase, exerts a dominant negative effect on C to U RNA editing. Am J Physiol Cell Physiol. 2001;281:C1904-C1916.

    Article  CAS  PubMed  Google Scholar 

  24. Muramatsu M, Sankaranand VS, Anant S, et al. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells. J Biol Chem. 1999;274:18470–18476.

    Article  CAS  PubMed  Google Scholar 

  25. Navaratnam N, Morrison JR, Bhattacharya S, et al. The p27 catalytic subunit of the apolipoprotein B mRNA editing enzyme is a cytidine deaminase. J Biol Chem. 1993;268:20709–20712.

    CAS  PubMed  Google Scholar 

  26. Yamanaka S, Poksay KS, Balestra ME, Zeng GQ, Innerarity TL. Cloning and mutagenesis of the rabbit ApoB mRNA editing protein: a zinc motif is essential for catalytic activity, and noncatalytic auxiliary factor(s) of the editing complex are widely distributed. J Biol Chem. 1994;269:21725–21734.

    CAS  PubMed  Google Scholar 

  27. Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell. 2000;102:553–563.

    Article  CAS  PubMed  Google Scholar 

  28. Mariani R, Chen D, Schrofelbauer B, et al. Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell. 2003;114:21–31.

    Article  CAS  PubMed  Google Scholar 

  29. Yu Q, Konig R, Pillai S, et al. Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome. Nat Struct Mol Biol. 2004;11:435–442.

    Article  CAS  PubMed  Google Scholar 

  30. Igakura T, Stinchcombe JC, Goon PK, et al. Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton. Science. 2003;299:1713–1716.

    Article  CAS  PubMed  Google Scholar 

  31. Noguchi C, Ishino H, Tsuge M, et al. G to A hypermutation of hepatitis B virus. Hepatology. 2005;41:626–633.

    Article  CAS  PubMed  Google Scholar 

  32. Gunther S, Sommer G, Plikat U, et al. Naturally occurring hepatitis B virus genomes bearing the hallmarks of retroviral G→A hypermutation. Virology. 1997;235:104–108.

    Article  CAS  PubMed  Google Scholar 

  33. Rosler C, Kock J, Malim MH, Blum HE, von Weizsacker F. Comment on “Inhibition of hepatitis B virus replication by APOBEC3G.” Science. 2004;305:1403.

    Article  PubMed  Google Scholar 

  34. Tanaka Y, Marysawa H, Seno H, et al. Anti-viral protein APOBEC3G is induced by interferon-α stimulation in human hepatocytes. Biochem Biophys Res Commun. 2006;341;314–319.

    Article  CAS  PubMed  Google Scholar 

  35. Turelli P, Vianin S, Trono D. The innate antiretroviral factor APOBEC3G does not affect human LINE-1 retrotransposition in a cell culture assay. J Biol Chem. 2004;279:43371–43373.

    Article  CAS  PubMed  Google Scholar 

  36. Zheng Y-H, Irwin D, Kurosu T, Tokunaga K, Sata T, Peterlin BM. Human APOBEC3F is another host factor that blocks human immunodeficiency virus type 1 replication. J Virol. 2004;78:6073–6076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wiegand HL, Doehle BP, Bogerd HP, Cullen BR. A second human antiretroviral factor, APOBEC3F, is suppressed by the HIV-1 and HIV-2 Vif proteins. EMBO J. 2004;23:2451–2458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Liddament MT, Brown WL, Schumacher AJ, Harris RS. APOBEC3F properties and hypermutation preferences indicate activity against HIV-1 in vivo. Curr Biol. 2004;14:1385–1391.

    Article  CAS  PubMed  Google Scholar 

  39. Shirakawa K, Takaori-Kondo A, Kobayashi M, et al. Ubiquitination of APOBEC3 proteins by the Vif-Cullin5-ElonginB-ElonginC complex. Virology. 2006;344:263–266.

    Article  CAS  PubMed  Google Scholar 

  40. Doehle BP, Schafer A, Cullen BR. Human APOBEC3B is a potent inhibitor of HIV-1 infectivity and is resistant to HIV-1 Vif. Virology. 2005;339:281–288.

    Article  CAS  PubMed  Google Scholar 

  41. Yu Q, Chen D, Konig R, Mariani R, Unutmaz D, Landau NR. APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication. J Biol Chem. 2004;279:53379–53386.

    Article  CAS  PubMed  Google Scholar 

  42. Bishop KN, Holmes RK, Sheehy AM, Malim MH. APOBEC-mediated editing of viral RNA. Science. 2004;305:645.

    Article  CAS  PubMed  Google Scholar 

  43. Harris RS, Sheehy AM, Craig HM, Malim MH, Neuberger MS. DNA deamination: not just a trigger for antibody diversification but also a mechanism for defense against retroviruses. Nat Immunol. 2003;4:641–643.

    Article  CAS  PubMed  Google Scholar 

  44. Doehle BP, Schafer A, Wiegand HL, Bogerd HP, Cullen BR. Differential sensitivity of murine leukemia virus to APOBEC3-mediated inhibition is governed by virion exclusion. J Virol. 2005;79:8201–8207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Alce TM, Popik W. APOBEC3G is incorporated into virus-like particles by a direct interaction with HIV-1 Gag nucleocapsid protein. J Biol Chem. 2004;279:34083–34086.

    Article  CAS  PubMed  Google Scholar 

  46. Cen S, Guo F, Niu M, Saadatmand J, Deflassieux J, Kleiman L. The interaction between HIV-1 Gag and APOBEC3G. J Biol Chem. 2004;279:33177–33184.

    Article  CAS  PubMed  Google Scholar 

  47. Luo K, Liu B, Xiao Z, et al. Amino-terminal region of the human immunodeficiency virus type 1 nucleocapsid is required for human APOBEC3G packaging. J Virol. 2004;78:11841–11852.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaracho, Sakyo-ku, 606-8507, Kyoto, Japan

    Akifumi Takaori-Kondo

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  1. Akifumi Takaori-Kondo
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Correspondence to Akifumi Takaori-Kondo.

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Takaori-Kondo, A. APOBEC Family Proteins: Novel Antiviral Innate Immunity. Int J Hematol 83, 213–216 (2006). https://doi.org/10.1532/IJH97.05187

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  • DOI: https://doi.org/10.1532/IJH97.05187

Key words

  • APOBEC
  • Human immunodeficiency virus
  • Hepatitis B virus
  • Cytidine deaminase
  • Innate immunity
  • Retrotransposon