Biopolym. Cell. 2000; 16(6):547-558.
http://dx.doi.org/10.7124/bc.000596
Viruses and Cell
Compositional specificity of human T-cell leukemia virus type I and human immunodeficiency virus type 1 integration into the human genome
1Tsyba L. O., 1Zoubak S. V., 2Tryapitsina-Guley N., 2Bernardi G., 1Rynditch A. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Institut Jacques Monod, CNRS-Universite Paris VII
    2 Place Jussieu, Paris, France, 75005

Abstract

Localization of HTLV-1 (human T-cell leukemia virus type I) and H1V-1 (human immunodeficiency virus type 1) proviral sequences in compositional compartments of genomes of patients with different manifestation of infection have been studied by a new technique of centrifugation in shallow CsCl gradients with two buoyant density markers. The major peaks of distribution of GC-rich HTLV-I sequences in genomes of 18 patients were centered at GC-rich (> 44 % GC) regions of the human genome which usually account 30 % of the genome and contain transcriptionally active HTLV-I sequences (Zoubak et al. (1994) Gene 143, 155–163). In the case of patients with T-cell leukemia (ATL) viral sequences were not found below 44 % GC. Patients with TSP/HAM and asymptomatic carriers had a broader and multimodal distribution of HTLV-I (at 38–54,8 % GC) with minor peaks in GC-poorer regions. GC-poor HIV-1 proviruses were found in both GC-poor and GC-rich compartments of genomes of 27 patients with different levels of virus production. More intense peaks were centered at GC-rich regions for the patients with lower virus load. These results have revealed that the distribution of integrated proviruses in vivo is nonuniform in the compositional compartments of cell genome and broader than in vitro.
Full text: (PDF, in Russian)

References

[1] Bernardi G. Isochores and the evolutionary genomics of vertebrates. Gene. 2000;241(1):3-17.
[2] Zoubak S, Clay O, Bernardi G. The gene distribution of the human genome. Gene. 1996;174(1):95-102.
[3] Kettmann R, Meunier-Rotival M, Cortadas J, Cuny G, Ghysdael J, Mammerickx M, Burny A, Bernardi G. Integration of bovine leukemia virus DNA in the bovine genome. Proc Natl Acad Sci U S A. 1979;76(10):4822-6.
[4] Rynditch A, Kadi F, Geryk J, Zoubak S, Svoboda J, Bernardi G. The isopycnic, compartmentalized integration of Rous sarcoma virus sequences. Gene. 1991;106(2):165-72.
[5] Zerial M, Salinas J, Filipski J, Bernardi G. Genomic localization of hepatitis B virus in a human hepatoma cell line. Nucleic Acids Res. 1986;14(21):8373-86.
[6] Zoubak S, Richardson JH, Rynditch A, H?llsberg P, Hafler DA, Boeri E, Lever AM, Bernardi G. Regional specificity of HTLV-I proviral integration in the human genome. Gene. 1994;143(2):155-63.
[7] Salinas J, Zerial M, Filipski J, Crepin M, Bernardi G. Nonrandom distribution of MMTV proviral sequences in the mouse genome. Nucleic Acids Res. 1987;15(7):3009-22.
[8] Zoubak S, Rynditch A, Bernardi G. Compositional bimodality and evolution of retroviral genomes. Gene. 1992;119(2):207-13.
[9] Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980;77(12):7415-9.
[10] Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T, Kinoshita KI, Shirakawa S, Miyoshi I. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981;78(10):6476-80.
[11] Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, de Th? G. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985;2(8452):407-10.
[12] Franchini G. Molecular mechanisms of human T-cell leukemia/lymphotropic virus type I infection. Blood. 1995;86(10):3619-39.
[13] Mellors JW, Rinaldo CR Jr, Gupta P, White RM, Todd JA, Kingsley LA. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science. 1996;272(5265):1167-70.
[14] Coffin JM. Retroviridae and their replication. Virology. Eds B. N. Fields, D. M. Knipe. New York, 1990: 1437-1500.
[15] Michael NL, Vahey M, Burke DS, Redfield RR. Viral DNA and mRNA expression correlate with the stage of human immunodeficiency virus (HIV) type 1 infection in humans: evidence for viral replication in all stages of HIV disease. J Virol. 1992;66(1):310-6.
[16] Winslow BJ, Pomerantz RJ, Bagasra O, Trono D. HIV-1 latency due to the site of proviral integration. Virology. 1993;196(2):849-54.
[17] Rynditch AV, Zoubak S, Tsyba L, Tryapitsina-Guley N, Bernardi G. The regional integration of retroviral sequences into the mosaic genomes of mammals. Gene. 1998;222(1):1-16.
[18] De Sario A, Geigl EM, Bernardi G. A rapid procedure for the compositional analysis of yeast artificial chromosomes. Nucleic Acids Res. 1995;23(19):4013-4.
[19] Fisher AG, Collalti E, Ratner L, Gallo RC, Wong-Staal F. A molecular clone of HTLV-III with biological activity. Nature. 1985 Jul 18-24;316(6025):262-5.
[20] Clarke MF, Gelmann EP, Reitz MS Jr. Homology of human T-cell leukaemia virus envelope gene with class I HLA gene. Nature. 1983 Sep 1-7;305(5929):60-2.
[21] Macaya G, Thiery JP, Bernardi G. An approach to the organization of eukaryotic genomes at a macromolecular level. J Mol Biol. 1976;108(1):237-54.
[22] Thiery JP, Macaya G, Bernardi G. An analysis of eukaryotic genomes by density gradient centrifugation. J Mol Biol. 1976;108(1):219-35.
[23] Schildkraut CL, Marmur J, Doty P. Determination of the base composition of deoxyribonucleic acid from its buoyant density in CsCl. J Mol Biol. 1962;4:430-43.
[24] Shinzato O, Ikeda S, Momita S, Nagata Y, Kamihira S, Nakayama E, Shiku H. Semiquantitative analysis of integrated genomes of human T-lymphotropic virus type I in asymptomatic virus carriers. Blood. 1991;78(8):2082-8.
[25] Etoh K, Tamiya S, Yamaguchi K, Okayama A, Tsubouchi H, Ideta T, Mueller N, Takatsuki K, Matsuoka M. Persistent clonal proliferation of human T-lymphotropic virus type I-infected cells in vivo. Cancer Res. 1997;57(21):4862-7.
[26] Gessain A, Saal F, Gout O, Daniel MT, Flandrin G, de The G, Peries J, Sigaux F. High human T-cell lymphotropic virus type I proviral DNA load with polyclonal integration in peripheral blood mononuclear cells of French West Indian, Guianese, and African patients with tropical spastic paraparesis. Blood. 1990;75(2):428-33.
[27] Yoshida M, Osame M, Kawai H, Toita M, Kuwasaki N, Nishida Y, Hiraki Y, Takahashi K, Nomura K, Sonoda S, et al. Increased replication of HTLV-I in HTLV-I-associated myelopathy. Ann Neurol. 1989;26(3):331-5.
[28] Yoshida M, Seiki M, Yamaguchi K, Takatsuki K. Monoclonal integration of human T-cell leukemia provirus in all primary tumors of adult T-cell leukemia suggests causative role of human T-cell leukemia virus in the disease. Proc Natl Acad Sci U S A. 1984;81(8):2534-7.
[29] Cavrois M, Gessain A, Wain-Hobson S, Wattel E. Proliferation of HTLV-1 infected circulating cells in vivo in all asymptomatic carriers and patients with TSP/HAM. Oncogene. 1996;12(11):2419-23.
[30] Wattel E, Vartanian JP, Pannetier C, Wain-Hobson S. Clonal expansion of human T-cell leukemia virus type I-infected cells in asymptomatic and symptomatic carriers without malignancy. J Virol. 1995;69(5):2863-8.
[31] Horwitz MS, Boyce-Jacino MT, Faras AJ. Novel human endogenous sequences related to human immunodeficiency virus type 1. J Virol. 1992;66(4):2170-9.
[32] Berneman ZN, Gartenhaus RB, Reitz MS Jr, Blattner WA, Manns A, Hanchard B, Ikehara O, Gallo RC, Klotman ME. Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers. Proc Natl Acad Sci U S A. 1992;89(7):3005-9.
[33] Kinoshita T, Shimoyama M, Tobinai K, Ito M, Ito S, Ikeda S, Tajima K, Shimotohno K, Sugimura T. Detection of mRNA for the tax1/rex1 gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989;86(14):5620-4.
[34] Okayama A, Korber B, Chen YM, Allan J, Lee TH, Shioiri S, Tachibana N, Tsuda K, Mueller N, McLane MF, et al. Unusual pattern of antibodies to human T-cell leukemia virus type-I in family members of adult T-cell leukemia patients. Blood. 1991;78(12):3323-9.
[35] Gessain A, Louie A, Gout O, Gallo RC, Franchini G. Human T-cell leukemia-lymphoma virus type I (HTLV-I) expression in fresh peripheral blood mononuclear cells from patients with tropical spastic paraparesis/HTLV-I-associated myelopathy. J Virol. 1991;65(3):1628-33.
[36] Beilke MA, In DR, Gravell M, Hamilton RS, Mora CA, Leon-Monzon M, Rodgers-Johnson PE, Gajdusek DC, Gibbs CJ Jr, Zaninovic V. In situ hybridization detection of HTLV-I RNA in peripheral blood mononuclear cells of TSP/HAM patients and their spouses. J Med Virol. 1991;33(1):64-71.
[37] Kerem BS, Goitein R, Diamond G, Cedar H, Marcus M. Mapping of DNAase I sensitive regions on mitotic chromosomes. Cell. 1984;38(2):493-9.
[38] Tazi J, Bird A. Alternative chromatin structure at CpG islands. Cell. 1990;60(6):909-20.
[39] Robinson HL, Gagnon GC. Patterns of proviral insertion and deletion in avian leukosis virus-induced lymphomas. J Virol. 1986;57(1):28-36.
[40] Vijaya S, Steffen DL, Robinson HL. Acceptor sites for retroviral integrations map near DNase I-hypersensitive sites in chromatin. J Virol. 1986;60(2):683-92.
[41] Rohdewohld H, Weiher H, Reik W, Jaenisch R, Breindl M. Retrovirus integration and chromatin structure: Moloney murine leukemia proviral integration sites map near DNase I-hypersensitive sites. J Virol. 1987;61(2):336-43.
[42] Scherdin U, Rhodes K, Breindl M. Transcriptionally active genome regions are preferred targets for retrovirus integration. J Virol. 1990;64(2):907-12.
[43] Mooslehner K, Karls U, Harbers K. Retroviral integration sites in transgenic Mov mice frequently map in the vicinity of transcribed DNA regions. J Virol. 1990;64(6):3056-8.
[44] Chou KS, Okayama A, Su IJ, Lee TH, Essex M. Preferred nucleotide sequence at the integration target site of human T-cell leukemia virus type I from patients with adult T-cell leukemia. Int J Cancer. 1996;65(1):20-4.
[45] Leclercq I, Mortreux F, Cavrois M, Leroy A, Gessain A, Wain-Hobson S, Wattel E. Host sequences flanking the human T-cell leukemia virus type 1 provirus in vivo. J Virol. 2000;74(5):2305-12.
[46] A?ssani B, D'Onofrio G, Mouchiroud D, Gardiner K, Gautier C, Bernardi G. The compositional properties of human genes. J Mol Evol. 1991;32(6):493-503.
[47] Bernardi G. The human genome: organization and evolutionary history. Annu Rev Genet. 1995;29:445-76. Review.