1887

Abstract

In the absence of the human immunodeficiency virus type 1 (HIV-1) Vif protein, the host-cell cytidine deaminases APOBEC3F and -3G are co-packaged along with virion RNA. Upon infection of target cells, nascent single-stranded DNA can be edited extensively, invariably giving rise to defective genomes called G→A hypermutants. Although human T-cell leukemia virus type 1 (HTLV-1) replicates in the same cell type as HIV-1, it was shown here that HTLV-1 is relatively resistant to the antiviral effects mediated by human APOBEC3B, -3C, -3F and -3G. Nonetheless, a small percentage of genomes (0·1<<5 %) were edited extensively: up to 97 % of cytidine targets were deaminated. In contrast, hypermutated HTLV-1 genomes were not identified in peripheral blood mononuclear cell DNA from ten patients with non-malignant HTLV-1 infection. Thus, although HTLV-1 DNA can indeed be edited by at least four APOBEC3 cytidine deaminases , they are conspicuously absent .

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80973-0
2005-09-01
2019-11-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/9/vir862489.html?itemId=/content/journal/jgv/10.1099/vir.0.80973-0&mimeType=html&fmt=ahah

References

  1. Beale, R. C. L., Petersen-Mahrt, S. K., Watt, I. N., Harris, R. S., Rada, C. & Neuberger, M. S. ( 2004; ). Comparison of the differential context-dependence of DNA deamination by APOBEC enzymes: correlation with mutation spectra in vivo. J Mol Biol 337, 585–596.[CrossRef]
    [Google Scholar]
  2. 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]
  3. Delebecque, F., Pramberger, K., Prévost, M.-C., Brahic, M. & Tangy, F. ( 2002; ). A chimeric human T-cell lymphotropic virus type 1 with the envelope glycoprotein of Moloney murine leukemia virus is infectious for murine cells. J Virol 76, 7883–7889.[CrossRef]
    [Google Scholar]
  4. Derse, D., Mikovits, J., Polianova, M., Felber, B. K. & Ruscetti, F. ( 1995; ). Virions released from cells transfected with a molecular clone of human T-cell leukemia virus type I give rise to primary and secondary infections of T cells. J Virol 69, 1907–1912.
    [Google Scholar]
  5. Fitzgibbon, J. E., Mazar, S. & Dubin, D. T. ( 1993; ). A new type of G→A hypermutation affecting human immunodeficiency virus. AIDS Res Hum Retroviruses 9, 833–838.[CrossRef]
    [Google Scholar]
  6. Gao, F., Yue, L., White, A. T. & 7 other authors ( 1992; ). Human infection by genetically diverse SIVSM-related HIV-2 in West Africa. Nature 358, 495–499.[CrossRef]
    [Google Scholar]
  7. Harris, R. S., Petersen-Mahrt, S. K. & Neuberger, M. S. ( 2002; ). RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Mol Cell 10, 1247–1253.[CrossRef]
    [Google Scholar]
  8. Harris, R. S., Bishop, K. N., Sheehy, A. M., Craig, H. M., Petersen-Mahrt, S. K., Watt, I. N., Neuberger, M. S. & Malim, M. H. ( 2003; ). DNA deamination mediates innate immunity to retroviral infection. Cell 113, 803–809.[CrossRef]
    [Google Scholar]
  9. Ho, D. D., Neumann, A. U., Perelson, A. S., Chen, W., Leonard, J. M. & Markowitz, M. ( 1995; ). Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373, 123–126.[CrossRef]
    [Google Scholar]
  10. Janini, M., Rogers, M., Birx, D. R. & McCutchan, F. E. ( 2001; ). Human immunodeficiency virus type 1 DNA sequences genetically damaged by hypermutation are often abundant in patient peripheral blood mononuclear cells and may be generated during near-simultaneous infection and activation of CD4+ T cells. J Virol 75, 7973–7986.[CrossRef]
    [Google Scholar]
  11. Lecossier, D., Bouchonnet, F., Clavel, F. & Hance, A. J. ( 2003; ). Hypermutation of HIV-1 DNA in the absence of the Vif protein. Science 300, 1112.[CrossRef]
    [Google Scholar]
  12. Liddament, M. T., Brown, W. L., Schumacher, A. J. & Harris, R. S. ( 2004; ). APOBEC3F properties and hypermutation preferences indicate activity against HIV-1 in vivo. Curr Biol 14, 1385–1391.[CrossRef]
    [Google Scholar]
  13. 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]
  14. Mansky, L. M. ( 2000; ). In vivo analysis of human T-cell leukemia virus type 1 reverse transcription accuracy. J Virol 74, 9525–9531.[CrossRef]
    [Google Scholar]
  15. Mariani, R., Chen, D., Schröfelbauer, B., Navarro, F., König, R., Bollman, B., Münk, 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]
  16. Pelletier, E., Saurin, W., Cheynier, R., Letvin, N. L. & Wain-Hobson, S. ( 1995; ). The tempo and mode of SIV quasispecies development in vivo calls for massive viral replication and clearance. Virology 208, 644–652.[CrossRef]
    [Google Scholar]
  17. Perelson, A. S., Neumann, A. U., Markowitz, M., Leonard, J. M. & Ho, D. D. ( 1996; ). HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271, 1582–1586.[CrossRef]
    [Google Scholar]
  18. Perry, S. T., Flaherty, M. T., Kelley, M. J., Clabough, D. L., Tronick, S. R., Coggins, L., Whetter, L., Lengel, C. R. & Fuller, F. ( 1992; ). The surface envelope protein gene region of equine infectious anemia virus is not an important determinant of tropism in vitro. J Virol 66, 4085–4097.
    [Google Scholar]
  19. Ribeiro, A. C., Maia e Silva, A., Santa-Marta, M., Pombo, A., Moniz-Pereira, J., Goncalves, J. & Barahona, I. ( 2005; ). Functional analysis of Vif protein shows less restriction of human immunodeficiency virus type 2 by APOBEC3G. J Virol 79, 823–833.[CrossRef]
    [Google Scholar]
  20. Royer-Leveau, C., Mordelet, E., Delebecque, F., Gessain, A., Charneau, P. & Ozden, S. ( 2002; ). Efficient transfer of HTLV-1 tax gene in various primary and immortalized cells using a flap lentiviral vector. J Virol Methods 105, 133–140.[CrossRef]
    [Google Scholar]
  21. Sova, P. & Volsky, D. J. ( 1993; ). Efficiency of viral DNA synthesis during infection of permissive and nonpermissive cells with vif-negative human immunodeficiency virus type 1. J Virol 67, 6322–6326.
    [Google Scholar]
  22. Suspène, R., Sommer, P., Henry, M. & 7 other authors ( 2004; ). APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase. Nucleic Acids Res 32, 2421–2429.[CrossRef]
    [Google Scholar]
  23. Suspène, R., Henry, M., Guillot, S., Wain-Hobson, S. & Vartanian, J.-P. ( 2005a; ). Recovery of APOBEC3-edited human immunodeficiency virus G→A hypermutants by differential DNA denaturation PCR. J Gen Virol 86, 125–129.[CrossRef]
    [Google Scholar]
  24. Suspène, R., Guétard, D., Henry, M., Sommer, P., Wain-Hobson, S. & Vartanian, J. P. ( 2005b; ). 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 102, 8321–8326.[CrossRef]
    [Google Scholar]
  25. Vartanian, J.-P., Meyerhans, A., Åsjö, B. & Wain-Hobson, S. ( 1991; ). Selection, recombination, and G→A hypermutation of human immunodeficiency virus type 1 genomes. J Virol 65, 1779–1788.
    [Google Scholar]
  26. Vartanian, J.-P., Plikat, U., Henry, M., Mahieux, R., Guillemot, L., Meyerhans, A. & Wain-Hobson, S. ( 1997; ). HIV genetic variation is directed and restricted by DNA precursor availability. J Mol Biol 270, 139–151.[CrossRef]
    [Google Scholar]
  27. Wain-Hobson, S., Sonigo, P., Guyader, M., Gazit, A. & Henry, M. ( 1995; ). Erratic G→A hypermutation within a complete caprine arthritis-encephalitis virus (CAEV) provirus. Virology 209, 297–303.[CrossRef]
    [Google Scholar]
  28. Wattel, E., Vartanian, J.-P., Pannetier, C. & Wain-Hobson, S. ( 1995; ). Clonal expansion of human T-cell leukemia virus type I-infected cells in asymptomatic and symptomatic carriers without malignancy. J Virol 69, 2863–2868.
    [Google Scholar]
  29. Wei, X., Ghosh, S. K., Taylor, M. E. & 9 other authors ( 1995; ). Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373, 117–122.[CrossRef]
    [Google Scholar]
  30. Wiegand, H. L., Doehle, B. P., Bogerd, H. P. & Cullen, B. R. ( 2004; ). A second human antiretroviral factor, APOBEC3F, is suppressed by the HIV-1 and HIV-2 Vif proteins. EMBO J 23, 2451–2458.[CrossRef]
    [Google Scholar]
  31. Yu, Q., Chen, D., König, R., Mariani, R., Unutmaz, D. & Landau, N. R. ( 2004a; ). APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication. J Biol Chem 279, 53379–53386.[CrossRef]
    [Google Scholar]
  32. Yu, Q., König, R., Pillai, S., Chiles, K., Kearney, M., Palmer, S., Richman, D., Coffin, J. M. & Landau, N. R. ( 2004b; ). Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome. Nat Struct Mol Biol 11, 435–442.[CrossRef]
    [Google Scholar]
  33. 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]
  34. Zheng, Y.-H., Irwin, D., Kurosu, T., Tokunaga, K., Sata, T. & Peterlin, B. M. ( 2004; ). Human APOBEC3F is another host factor that blocks human immunodeficiency virus type 1 replication. J Virol 78, 6073–6076.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80973-0
Loading
/content/journal/jgv/10.1099/vir.0.80973-0
Loading

Data & Media loading...

Supplements

Complete set of the 248 bp APOBEC3-edited sequences [PDF](143 KB)

PDF

Complete set of patient sequences [PDF](114 KB)

PDF

Substitution matrices for AT-rich variants amplified from PBMC DNA of three patients with non-malignant HTLV-1 disease [PDF](89 KB)

PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error