Abstract
Human T-cell leukemia virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-associated myelopathy. Both diseases are usually preceded by a long clinically asymptomatic period. PCR amplification of the HTLV-I proviral integration sites shows that clonal expansion of HTLV-I-bearing T cells, rather than being an occasional phenomenon in nonmalignant disease, is the norm for both symptomatic and asymptomatic carriers. Sequencing of 100 molecular clones derived by PCR amplification of part of the envelope gene from two asymptomatic carriers revealed almost no genetic variation. Viral amplification via clonal expansion, rather than by reverse transcription, would explain this remarkable genetic stability.
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- Cullen B. R. Mechanism of action of regulatory proteins encoded by complex retroviruses. Microbiol Rev. 1992 Sep;56(3):375–394. doi: 10.1128/mr.56.3.375-394.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Furukawa Y., Fujisawa J., Osame M., Toita M., Sonoda S., Kubota R., Ijichi S., Yoshida M. Frequent clonal proliferation of human T-cell leukemia virus type 1 (HTLV-1)-infected T cells in HTLV-1-associated myelopathy (HAM-TSP). Blood. 1992 Aug 15;80(4):1012–1016. [PubMed] [Google Scholar]
- Gessain A., Gallo R. C., Franchini G. Low degree of human T-cell leukemia/lymphoma virus type I genetic drift in vivo as a means of monitoring viral transmission and movement of ancient human populations. J Virol. 1992 Apr;66(4):2288–2295. doi: 10.1128/jvi.66.4.2288-2295.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gessain A., Saal F., Gout O., Daniel M. T., 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 Jan 15;75(2):428–433. [PubMed] [Google Scholar]
- Ho D. D., Moudgil T., Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med. 1989 Dec 14;321(24):1621–1625. doi: 10.1056/NEJM198912143212401. [DOI] [PubMed] [Google Scholar]
- Jacobson S., Shida H., McFarlin D. E., Fauci A. S., Koenig S. Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. Nature. 1990 Nov 15;348(6298):245–248. doi: 10.1038/348245a0. [DOI] [PubMed] [Google Scholar]
- Kira J., Koyanagi Y., Yamada T., Itoyama Y., Goto I., Yamamoto N., Sasaki H., Sakaki Y. Increased HTLV-I proviral DNA in HTLV-I-associated myelopathy: a quantitative polymerase chain reaction study. Ann Neurol. 1991 Feb;29(2):194–201. doi: 10.1002/ana.410290214. [DOI] [PubMed] [Google Scholar]
- Kubota R., Fujiyoshi T., Izumo S., Yashiki S., Maruyama I., Osame M., Sonoda S. Fluctuation of HTLV-I proviral DNA in peripheral blood mononuclear cells of HTLV-I-associated myelopathy. J Neuroimmunol. 1993 Feb;42(2):147–154. doi: 10.1016/0165-5728(93)90004-i. [DOI] [PubMed] [Google Scholar]
- Mansky L. M., Temin H. M. Lower mutation rate of bovine leukemia virus relative to that of spleen necrosis virus. J Virol. 1994 Jan;68(1):494–499. doi: 10.1128/jvi.68.1.494-499.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meyerhans A., Cheynier R., Albert J., Seth M., Kwok S., Sninsky J., Morfeldt-Månson L., Asjö B., Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 1989 Sep 8;58(5):901–910. doi: 10.1016/0092-8674(89)90942-2. [DOI] [PubMed] [Google Scholar]
- Pannetier C., Cochet M., Darche S., Casrouge A., Zöller M., Kourilsky P. The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4319–4323. doi: 10.1073/pnas.90.9.4319. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pedroza Martins L., Chenciner N., Wain-Hobson S. Complex intrapatient sequence variation in the V1 and V2 hypervariable regions of the HIV-1 gp 120 envelope sequence. Virology. 1992 Dec;191(2):837–845. doi: 10.1016/0042-6822(92)90259-r. [DOI] [PubMed] [Google Scholar]
- Richardson J. H., Edwards A. J., Cruickshank J. K., Rudge P., Dalgleish A. G. In vivo cellular tropism of human T-cell leukemia virus type 1. J Virol. 1990 Nov;64(11):5682–5687. doi: 10.1128/jvi.64.11.5682-5687.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz S., Felber B. K., Benko D. M., Fenyö E. M., Pavlakis G. N. Cloning and functional analysis of multiply spliced mRNA species of human immunodeficiency virus type 1. J Virol. 1990 Jun;64(6):2519–2529. doi: 10.1128/jvi.64.6.2519-2529.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seiki M., Hattori S., Hirayama Y., Yoshida M. Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618–3622. doi: 10.1073/pnas.80.12.3618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sherman M. P., Saksena N. K., Dube D. K., Yanagihara R., Poiesz B. J. Evolutionary insights on the origin of human T-cell lymphoma/leukemia virus type I (HTLV-I) derived from sequence analysis of a new HTLV-I variant from Papua New Guinea. J Virol. 1992 Apr;66(4):2556–2563. doi: 10.1128/jvi.66.4.2556-2563.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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 Oct 15;78(8):2082–2088. [PubMed] [Google Scholar]
- Triglia T., Peterson M. G., Kemp D. J. A procedure for in vitro amplification of DNA segments that lie outside the boundaries of known sequences. Nucleic Acids Res. 1988 Aug 25;16(16):8186–8186. doi: 10.1093/nar/16.16.8186. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vartanian J. P., Meyerhans A., Asjö B., Wain-Hobson S. Selection, recombination, and G----A hypermutation of human immunodeficiency virus type 1 genomes. J Virol. 1991 Apr;65(4):1779–1788. doi: 10.1128/jvi.65.4.1779-1788.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wain-Hobson S., Vartanian J. P., Henry M., Chenciner N., Cheynier R., Delassus S., Martins L. P., Sala M., Nugeyre M. T., Guétard D. LAV revisited: origins of the early HIV-1 isolates from Institut Pasteur. Science. 1991 May 17;252(5008):961–965. doi: 10.1126/science.2035026. [DOI] [PubMed] [Google Scholar]
- Wain-Hobson S. Viral burden in AIDS. Nature. 1993 Nov 4;366(6450):22–22. doi: 10.1038/366022b0. [DOI] [PubMed] [Google Scholar]
- Watanabe T., Seiki M., Tsujimoto H., Miyoshi I., Hayami M., Yoshida M. Sequence homology of the simian retrovirus genome with human T-cell leukemia virus type I. Virology. 1985 Jul 15;144(1):59–65. doi: 10.1016/0042-6822(85)90304-6. [DOI] [PubMed] [Google Scholar]
- Wattel E., Mariotti M., Agis F., Gordien E., Le Coeur F. F., Prin L., Rouger P., Chen I. S., Wain-Hobson S., Lefrere J. J. Quantification of HTLV-1 proviral copy number in peripheral blood of symptomless carriers from the French West Indies. J Acquir Immune Defic Syndr. 1992;5(9):943–946. [PubMed] [Google Scholar]
- Wattel E., Mariotti M., Agis F., Gordien E., Prou O., Courouce A. M., Rouger P., Wain-Hobson S., Chen I. S., Lefrère J. J. Human T lymphotropic virus (HTLV) type I and II DNA amplification in HTLV-I/II-seropositive blood donors of the French West Indies. J Infect Dis. 1992 Feb;165(2):369–372. doi: 10.1093/infdis/165.2.369. [DOI] [PubMed] [Google Scholar]
- Yoshida M. HTLV-1 Tax: regulation of gene expression and disease. Trends Microbiol. 1993 Jul;1(4):131–135. doi: 10.1016/0966-842x(93)90127-d. [DOI] [PubMed] [Google Scholar]
- Yoshida M., Osame M., Kawai H., Toita M., Kuwasaki N., Nishida Y., Hiraki Y., Takahashi K., Nomura K., Sonoda S. Increased replication of HTLV-I in HTLV-I-associated myelopathy. Ann Neurol. 1989 Sep;26(3):331–335. doi: 10.1002/ana.410260304. [DOI] [PubMed] [Google Scholar]
- 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 Apr;81(8):2534–2537. doi: 10.1073/pnas.81.8.2534. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhao T. M., Robinson M. A., Sawasdikosol S., Simpson R. M., Kindt T. J. Variation in HTLV-I sequences from rabbit cell lines with diverse in vivo effects. Virology. 1993 Jul;195(1):271–274. doi: 10.1006/viro.1993.1373. [DOI] [PubMed] [Google Scholar]