1887

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Volume 89, Issue 3

APOBEC3G upregulation by alpha interferon restricts human immunodeficiency virus type 1 infection in human peripheral plasmacytoid dendritic cells Free

Abstract

APOBEC3G (A3G), a member of cytidine deaminase family, has potent anti-human immunodeficiency virus type 1 (HIV-1) activity. It has been demonstrated that alpha interferon (IFN-) can significantly enhance the expression of A3G in human primary resting CD4 T-cells, macrophages and primary hepatocytes, subsequently decreasing their viral susceptibility. Plasmacytoid dendritic cells (pDCs) are key effectors in innate host immunity, mediating adaptive immune responses and stimulating IFN- production in reaction to various stimuli. In this report, we demonstrate that IFN-, either exogenously added to- or endogenously secreted by pDCs, can enhance the expression of A3G and its family members such as A3A, A3C and A3F. We have also shown that IFN- can inhibit HIV-1 expression in pDCs. This inhibitory effect could be countered by addition of an A3G-specific short interfering RNA, indicating that IFN--induced A3G plays a key role in mediating pDCs response to HIV-1. Given the central role played by pDCs in orchestrating the IFN-/A3G intercellular network and intracellular signal pathway, our data indicate that pDCs themselves are also protected by an IFN-/A3G-mediated innate immunity barrier from HIV-1 infection.

  • Received:
  • Accepted:
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2008-03-01
2024-04-19
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References

  1. Abe T., Hemmi H., Miyamoto H., Moriishi K., Tamura S., Takaku H., Akira S., Matsuura Y. 2005; Involvement of the Toll-like receptor 9 signaling pathway in the induction of innate immunity by baculovirus. J Virol 79:2847–2858 [CrossRef]
     [Google Scholar]
  2. Almeida M., Cordero M., Almeida J., Orfao A. 2006; Persistent abnormalities in peripheral blood dendritic cells and monocytes from HIV-1-positive patients after 1 year of antiretroviral therapy. J Acquir Immune Defic Syndr 41:405–415 [CrossRef]
     [Google Scholar]
  3. Bauer S., Kirschning C. J., Hacker H., Redecke V., Hausmann S., Akira S., Wagner H., Lipford G. B. 2001; Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci U S A 98:9237–9242 [CrossRef]
     [Google Scholar]
  4. Beignon A. S., McKenna K., Skoberne M., Manches O., DaSilva I., Kavanagh D. G., Larsson M., Gorelick R. J., Lifson J. D., Bhardwaj N. 2005; Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions. J Clin Invest 115:3265–3275 [CrossRef]
     [Google Scholar]
  5. Berglund O., Engman K., Ehrnst A., Andersson J., Lidman K., Akerlund B., Sonnerborg A., Strannegard O. 1991; Combined treatment of symptomatic human immunodeficiency virus type 1 infection with native interferon-alpha and zidovudine. J Infect Dis 163:710–715 [CrossRef]
     [Google Scholar]
  6. Bishop K. N., Holmes R. K., Sheehy A. M., Davidson N. O., Cho S. J., Malim M. H. 2004; Cytidine deamination of retroviral DNA by diverse APOBEC proteins. Curr Biol 14:1392–1396 [CrossRef]
     [Google Scholar]
  7. Bonvin M., Achermann F., Greeve I., Stroka D., Keogh A., Inderbitzin D., Candinas D., Sommer P., Wain-Hobson S. other authors 2006; Interferon-inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication. Hepatology 43:1364–1374 [CrossRef]
     [Google Scholar]
  8. Butler S. L., Hansen M. S., Bushman F. D. 2001; A quantitative assay for HIV DNA integration in vivo . Nat Med 7:631–634 [CrossRef]
     [Google Scholar]
  9. Cella M., Jarrossay D., Facchetti F., Alebardi O., Nakajima H., Lanzavecchia A., Colonna M. 1999; Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med 5:919–923 [CrossRef]
     [Google Scholar]
  10. Cella M., Facchetti F., Lanzavecchia A., Colonna M. 2000; Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization. Nat Immunol 1:305–310 [CrossRef]
     [Google Scholar]
  11. Chehimi J., Campbell D. E., Azzoni L., Bacheller D., Papasavvas E., Jerandi G., Mounzer K., Kostman J., Trinchieri G., Montaner L. J. 2002; Persistent decreases in blood plasmacytoid dendritic cell number and function despite effective highly active antiretroviral therapy and increased blood myeloid dendritic cells in HIV-infected individuals. J Immunol 168:4796–4801 [CrossRef]
     [Google Scholar]
  12. Chen K., Huang J., Zhang C., Huang S., Nunnari G., Wang F. X., Tong X., Gao L., Nikisher K., Zhang H. 2006; Alpha interferon potently enhances the anti-human immunodeficiency virus type 1 activity of APOBEC3G in resting primary CD4 T cells. J Virol 80:7645–7657 [CrossRef]
     [Google Scholar]
  13. Chiu Y. L., Soros V. B., Kreisberg J. F., Stopak K., Yonemoto W., Greene W. C. 2005; Cellular APOBEC3G restricts HIV-1 infection in resting CD4+ T cells. Nature 435:108–114 [CrossRef]
     [Google Scholar]
  14. Del Corno M., Gauzzi M. C., Penna G., Belardelli F., Adorini L., Gessani S. 2005; Human immunodeficiency virus type 1 gp120 and other activation stimuli are highly effective in triggering alpha interferon and CC chemokine production in circulating plasmacytoid but not myeloid dendritic cells. J Virol 79:12597–12601 [CrossRef]
     [Google Scholar]
  15. Djeu J. Y., Stocks N., Zoon K., Stanton G. J., Timonen T., Herberman R. B. 1982; Positive self regulation of cytotoxicity in human natural killer cells by production of interferon upon exposure to influenza and herpes viruses. J Exp Med 156:1222–1234 [CrossRef]
     [Google Scholar]
  16. Doehle B. P., Schafer A., Wiegand H. L., Bogerd H. P., Cullen B. R. 2005; Differential sensitivity of murine leukemia virus to APOBEC3-mediated inhibition is governed by virion exclusion. J Virol 79:8201–8207 [CrossRef]
     [Google Scholar]
  17. Donaghy H., Pozniak A., Gazzard B., Qazi N., Gilmour J., Gotch F., Patterson S. 2001; Loss of blood CD11c+ myeloid and CD11c− plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load. Blood 98:2574–2576 [CrossRef]
     [Google Scholar]
  18. Dzionek A., Sohma Y., Nagafune J., Cella M., Colonna M., Facchetti F., Gunther G., Johnston I., Lanzavecchia A. other authors 2001; BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon α / β induction. J Exp Med 194:1823–1834 [CrossRef]
     [Google Scholar]
  19. Esnault C., Heidmann O., Delebecque F., Dewannieux M., Ribet D., Hance A. J., Heidmann T., Schwartz O. 2005; APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses. Nature 433:430–433 [CrossRef]
     [Google Scholar]
  20. Feldman S., Stein D., Amrute S., Denny T., Garcia Z., Kloser P., Sun Y., Megjugorac N., Fitzgerald-Bocarsly P. 2001; Decreased interferon- α production in HIV-infected patients correlates with numerical and functional deficiencies in circulating type 2 dendritic cell precursors. Clin Immunol 101:201–210 [CrossRef]
     [Google Scholar]
  21. Fong L., Mengozzi M., Abbey N. W., Herndier B. G., Engleman E. G. 2002; Productive infection of plasmacytoid dendritic cells with human immunodeficiency virus type 1 is triggered by CD40 ligation. J Virol 76:11033–11041 [CrossRef]
     [Google Scholar]
  22. Fonteneau J. F., Larsson M., Beignon A. S., McKenna K., Dasilva I., Amara A., Liu Y. J., Lifson J. D., Littman D. R., Bhardwaj N. 2004; Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells. J Virol 78:5223–5232 [CrossRef]
     [Google Scholar]
  23. Grouard G., Rissoan M. C., Filgueira L., Durand I., Banchereau J., Liu Y. J. 1997; The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. J Exp Med 185:1101–1111 [CrossRef]
     [Google Scholar]
  24. Gurney K. B., Colantonio A. D., Blom B., Spits H., Uittenbogaart C. H. 2004; Endogenous IFN- α production by plasmacytoid dendritic cells exerts an antiviral effect on thymic HIV-1 infection. J Immunol 173:7269–7276 [CrossRef]
     [Google Scholar]
  25. Hemmi H., Takeuchi O., Kawai T., Kaisho T., Sato S., Sanjo H., Matsumoto M., Hoshino K., Wagner H. other authors 2000; A Toll-like receptor recognizes bacterial DNA. Nature 408:740–745 [erratum appears in Nature ] 2001409–646 [CrossRef]
     [Google Scholar]
  26. Hornung V., Rothenfusser S., Britsch S., Krug A., Jahrsdorfer B., Giese T., Endres S., Hartmann G. 2002; Quantitative expression of toll-like receptor 1–10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol 168:4531–4537 [CrossRef]
     [Google Scholar]
  27. Jarmuz A., Chester A., Bayliss J., Gisbourne J., Dunham I., Scott J., Navaratnam N. 2002; An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22. Genomics 79:285–296 [CrossRef]
     [Google Scholar]
  28. Jego G., Palucka A. K., Blanck J. P., Chalouni C., Pascual V., Banchereau J. 2003; Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 19:225–234 [CrossRef]
     [Google Scholar]
  29. Kadowaki N., Antonenko S., Lau J. Y., Liu Y. J. 2000; Natural interferon α / β -producing cells link innate and adaptive immunity. J Exp Med 192:219–226 [CrossRef]
     [Google Scholar]
  30. Kadowaki N., Ho S., Antonenko S., Malefyt R. W., Kastelein R. A., Bazan F., Liu Y. J. 2001; Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med 194:863–869 [CrossRef]
     [Google Scholar]
  31. Kamga I., Kahi S., Develioglu L., Lichtner M., Maranon C., Deveau C., Meyer L., Goujard C., Lebon P. other authors 2005; Type I interferon production is profoundly and transiently impaired in primary HIV-1 infection. J Infect Dis 192:303–310 [CrossRef]
     [Google Scholar]
  32. Killian M. S., Fujimura S. H., Hecht F. M., Levy J. A. 2006; Similar changes in plasmacytoid dendritic cell and CD4 T-cell counts during primary HIV-1 infection and treatment. AIDS 20:1247–1252 [CrossRef]
     [Google Scholar]
  33. Mangeat B., Turelli P., Caron G., Friedli M., Perrin L., Trono D. 2003; Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 424:99–103 [CrossRef]
     [Google Scholar]
  34. Mangeat B., Turelli P., Liao S., Trono D. 2004; A single amino acid determinant governs the species-specific sensitivity of APOBEC3G to Vif action. J Biol Chem 279:14481–14483 [CrossRef]
     [Google Scholar]
  35. Mariani R., Chen D., Schrofelbauer B., Navarro F., Konig R., Bollman B., Munk C., Nymark-McMahon H., Landau N. R. 2003; Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell 114:21–31 [CrossRef]
     [Google Scholar]
  36. Marin M., Rose K. M., Kozak S. L., Kabat D. 2003; HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nat Med 9:1398–1403 [CrossRef]
     [Google Scholar]
  37. McKenna K., Beignon A. S., Bhardwaj N. 2005; Plasmacytoid dendritic cells: linking innate and adaptive immunity. J Virol 79:17–27 [CrossRef]
     [Google Scholar]
  38. Noguchi C., Ishino H., Tsuge M., Fujimoto Y., Imamura M., Takahashi S., Chayama K. 2005; G to A hypermutation of hepatitis B virus. Hepatology 41:626–633 [CrossRef]
     [Google Scholar]
  39. Patterson S., Rae A., Hockey N., Gilmour J., Gotch F. 2001; Plasmacytoid dendritic cells are highly susceptible to human immunodeficiency virus type 1 infection and release infectious virus. J Virol 75:6710–6713 [CrossRef]
     [Google Scholar]
  40. Peng G., Lei K. J., Jin W., Greenwell-Wild T., Wahl S. M. 2006; Induction of APOBEC3 family proteins, a defensive maneuver underlying interferon-induced anti-HIV-1 activity. J Exp Med 203:41–46 [CrossRef]
     [Google Scholar]
  41. Rissoan M. C., Soumelis V., Kadowaki N., Grouard G., Briere F., de Waal Malefyt R., Liu Y. J. 1999; Reciprocal control of T helper cell and dendritic cell differentiation. Science 283:1183–1186 [CrossRef]
     [Google Scholar]
  42. Rosler C., Kock J., Kann M., Malim M. H., Blum H. E., Baumert T. F., von Weizsacker F. 2005; APOBEC-mediated interference with hepadnavirus production. Hepatology 42:301–309
     [Google Scholar]
  43. Sarkis P. T., Ying S., Xu R., Yu X. F. 2006; STAT1-independent cell type-specific regulation of antiviral APOBEC3G by IFN- α . J Immunol 177:4530–4540 [CrossRef]
     [Google Scholar]
  44. Sasada A., Takaori-Kondo A., Shirakawa K., Kobayashi M., Abudu A., Hishizawa M., Imada K., Tanaka Y., Uchiyama T. 2005; APOBEC3G targets human T-cell leukemia virus type 1. Retrovirology 2:32 [CrossRef]
     [Google Scholar]
  45. Schlaepfer E., Audige A., von Beust B., Manolova V., Weber M., Joller H., Bachmann M. F., Kundig T. M., Speck R. F. 2004; CpG oligodeoxynucleotides block human immunodeficiency virus type 1 replication in human lymphoid tissue infected ex vivo. J Virol 78:12344–12354 [CrossRef]
     [Google Scholar]
  46. Schmidt B., Scott I., Whitmore R. G., Foster H., Fujimura S., Schmitz J., Levy J. A. 2004; Low-level HIV infection of plasmacytoid dendritic cells: onset of cytopathic effects and cell death after PDC maturation. Virology 329:280–288 [CrossRef]
     [Google Scholar]
  47. Schmidt B., Ashlock B. M., Foster H., Fujimura S. H., Levy J. A. 2005; HIV-infected cells are major inducers of plasmacytoid dendritic cell interferon production, maturation, and migration. Virology 343:256–266 [CrossRef]
     [Google Scholar]
  48. Sheehy A. M., Gaddis N. C., Choi J. D., Malim M. H. 2002; Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418:646–650 [CrossRef]
     [Google Scholar]
  49. Sheehy A. M., Gaddis N. C., Malim M. H. 2003; The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med 9:1404–1407 [CrossRef]
     [Google Scholar]
  50. Siegal F. P., Kadowaki N., Shodell M., Fitzgerald-Bocarsly P. A., Shah K., Ho S., Antonenko S., Liu Y. J. 1999; The nature of the principal type 1 interferon-producing cells in human blood. Science 284:1835–1837 [CrossRef]
     [Google Scholar]
  51. Soumelis V., Scott I., Gheyas F., Bouhour D., Cozon G., Cotte L., Huang L., Levy J. A., Liu Y. J. 2001; Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients. Blood 98:906–912 [CrossRef]
     [Google Scholar]
  52. Tanaka Y., Marusawa H., Seno H., Matsumoto Y., Ueda Y., Kodama Y., Endo Y., Yamauchi J., Matsumoto T. other authors 2006; Anti-viral protein APOBEC3G is induced by interferon- α stimulation in human hepatocytes. Biochem Biophys Res Commun 341:314–319 [CrossRef]
     [Google Scholar]
  53. Turelli P., Mangeat B., Jost S., Vianin S., Trono D. 2004; Inhibition of hepatitis B virus replication by APOBEC3G. Science 303:1829 [CrossRef]
     [Google Scholar]
  54. Wagner H. 2002; Interactions between bacterial CpG-DNA and TLR9 bridge innate and adaptive immunity. Curr Opin Microbiol 5:62–69 [CrossRef]
     [Google Scholar]
  55. Wang F. X., Xu Y., Sullivan J., Souder E., Argyris E. G., Acheampong E. A., Fisher J., Sierra M., Thomson M. M. other authors 2005; IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART. J Clin Invest 115:128–137 [CrossRef]
     [Google Scholar]
  56. Yu X., Yu Y., Liu B., Luo K., Kong W., Mao P., Yu X. F. 2003; Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science 302:1056–1060 [CrossRef]
     [Google Scholar]
  57. Yu Q., Chen D., Konig R., Mariani R., Unutmaz D., Landau N. R. 2004; APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication. J Biol Chem 279:53379–53386 [CrossRef]
     [Google Scholar]
  58. Zhang H., Yang B., Pomerantz R. J., Zhang C., Arunachalam S. C., Gao L. 2003; The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 424:94–98 [CrossRef]
     [Google Scholar]
  59. Zhang H., Zhou Y., Alcock C., Kiefer T., Monie D., Siliciano J., Li Q., Pham P., Cofrancesco J. other authors 2004; Novel single-cell-level phenotypic assay for residual drug susceptibility and reduced replication capacity of drug-resistant human immunodeficiency virus type 1. J Virol 78:1718–1729 [CrossRef]
     [Google Scholar]
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APOBEC3G upregulation by alpha interferon restricts human immunodeficiency virus type 1 infection in human peripheral plasmacytoid dendritic cells
J. Gen. Virol. 89, 722 (2008); https://doi.org/10.1099/vir.0.83530-0
/content/journal/jgv/10.1099/vir.0.83530-0
/content/journal/jgv/10.1099/vir.0.83530-0
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