Abstract
Human T-cell leukemia virus (HTLV) is a family of related human T-lymphotropic retroviruses closely linked with certain human T-cell malignancies and associated with many cases of acquired immunodeficiency syndrome (AIDS). We isolated and molecularly cloned HTLV from patients with both types of clinical disorders and found by restriction endonuclease mapping and core and envelope protein analysis that at least two evolutionarily divergent viral subgroups exist, HTLV-I and HTLV-II. Previous studies have failed to detect significant nucleotide sequence homology between HTLV-I and HTLV-II even though these different members of the HTLV family share certain biologic properties such as T-cell tropism and transformation. To further test these viruses for conserved regions in their genomes, we examined hybridization between HTLV-I and HTLV-II by using Southern blotting and heteroduplex mapping at different melting points. These two techniques produced similar results, showing that HTLV-I and HTLV-II proviruses have, in fact, strongly conserved nucleotide sequences in the pX region and lesser although still substantial homology in the LTR, gag, pol, and env regions. These data provide experimental evidence that HTLV-II, like HTLV-I, contains pX sequences. Although the function of pX is unknown, its conservation in evolutionarily divergent human T-lymphotropic viruses implies a biologically important function. It is possible, but unproven, that pX could encode proteins involved in T-cell tropism, cell transformation, immune suppression, or other biologic actions characteristic of the HTLV family.
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- Chen I. S., McLaughlin J., Gasson J. C., Clark S. C., Golde D. W. Molecular characterization of genome of a novel human T-cell leukaemia virus. Nature. 1983 Oct 6;305(5934):502–505. doi: 10.1038/305502a0. [DOI] [PubMed] [Google Scholar]
- Davis R. W., Hyman R. W. A study in evolution: the DNA base sequence homology between coliphages T7 and T3. J Mol Biol. 1971 Dec 14;62(2):287–301. doi: 10.1016/0022-2836(71)90428-1. [DOI] [PubMed] [Google Scholar]
- Essex M., McLane M. F., Lee T. H., Falk L., Howe C. W., Mullins J. I., Cabradilla C., Francis D. P. Antibodies to cell membrane antigens associated with human T-cell leukemia virus in patients with AIDS. Science. 1983 May 20;220(4599):859–862. doi: 10.1126/science.6342136. [DOI] [PubMed] [Google Scholar]
- Gallo R. C., Sarin P. S., Gelmann E. P., Robert-Guroff M., Richardson E., Kalyanaraman V. S., Mann D., Sidhu G. D., Stahl R. E., Zolla-Pazner S. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):865–867. doi: 10.1126/science.6601823. [DOI] [PubMed] [Google Scholar]
- Gelmann E. P., Franchini G., Manzari V., Wong-Staal F., Gallo R. C. Molecular cloning of a unique human T-cell leukemia virus (HTLV-IIMo). Proc Natl Acad Sci U S A. 1984 Feb;81(4):993–997. doi: 10.1073/pnas.81.4.993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gelmann E. P., Popovic M., Blayney D., Masur H., Sidhu G., Stahl R. E., Gallo R. C. Proviral DNA of a retrovirus, human T-cell leukemia virus, in two patients with AIDS. Science. 1983 May 20;220(4599):862–865. doi: 10.1126/science.6601822. [DOI] [PubMed] [Google Scholar]
- Guo H. G., Wong-Stall F., Gallo R. C. Novel viral sequences related to human T-cell leukemia virus in T cells of a seropositive baboon. Science. 1984 Mar 16;223(4641):1195–1197. doi: 10.1126/science.6322297. [DOI] [PubMed] [Google Scholar]
- Howley P. M., Israel M. A., Law M. F., Martin M. A. A rapid method for detecting and mapping homology between heterologous DNAs. Evaluation of polyomavirus genomes. J Biol Chem. 1979 Jun 10;254(11):4876–4883. [PubMed] [Google Scholar]
- Hyman R. W., Brunovskis I., Summers W. C. DNA base sequence homology between coliphages T7 and phiII and between T3 and phiII as determined by heteroduplex mapping in the electron microscope. J Mol Biol. 1973 Jun 25;77(2):189–196. doi: 10.1016/0022-2836(73)90330-6. [DOI] [PubMed] [Google Scholar]
- Kalyanaraman V. S., Sarngadharan M. G., Robert-Guroff M., Miyoshi I., Golde D., Gallo R. C. A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science. 1982 Nov 5;218(4572):571–573. doi: 10.1126/science.6981847. [DOI] [PubMed] [Google Scholar]
- Mann D. L., Popovic M., Murray C., Neuland C., Strong D. M., Sarin P., Gallo R. C., Blattner W. A. Cell surface antigen expression in newborn cord blood lymphocytes infected with HTLV. J Immunol. 1983 Oct;131(4):2021–2024. [PubMed] [Google Scholar]
- Markham P. D., Salahuddin S. Z., Macchi B., Robert-Guroff M., Gallo R. C. Transformation of different phenotypic types of human bone marrow T-lymphocytes by HTLV-1. Int J Cancer. 1984 Jan 15;33(1):13–17. doi: 10.1002/ijc.2910330104. [DOI] [PubMed] [Google Scholar]
- McConaughy B. L., Laird C. D., McCarthy B. J. Nucleic acid reassociation in formamide. Biochemistry. 1969 Aug;8(8):3289–3295. doi: 10.1021/bi00836a024. [DOI] [PubMed] [Google Scholar]
- Miyoshi I., Kubonishi I., Yoshimoto S., Akagi T., Ohtsuki Y., Shiraishi Y., Nagata K., Hinuma Y. Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells. Nature. 1981 Dec 24;294(5843):770–771. doi: 10.1038/294770a0. [DOI] [PubMed] [Google Scholar]
- Miyoshi I., Yoshimoto S., Fujishita M., Taguchi H., Kubonishi I., Niiya K., Minezawa M. Natural adult T-cell leukemia virus infection in Japanese monkeys. Lancet. 1982 Sep 18;2(8299):658–658. doi: 10.1016/s0140-6736(82)92757-x. [DOI] [PubMed] [Google Scholar]
- Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. 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 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Poiesz B. J., Ruscetti F. W., Reitz M. S., Kalyanaraman V. S., Gallo R. C. Isolation of a new type C retrovirus (HTLV) in primary uncultured cells of a patient with Sézary T-cell leukaemia. Nature. 1981 Nov 19;294(5838):268–271. doi: 10.1038/294268a0. [DOI] [PubMed] [Google Scholar]
- Popovic M., Lange-Wantzin G., Sarin P. S., Mann D., Gallo R. C. Transformation of human umbilical cord blood T cells by human T-cell leukemia/lymphoma virus. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5402–5406. doi: 10.1073/pnas.80.17.5402. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Popovic M., Reitz M. S., Jr, Sarngadharan M. G., Robert-Guroff M., Kalyanaraman V. S., Nakao Y., Miyoshi I., Minowada J., Yoshida M., Ito Y. The virus of Japanese adult T-cell leukaemia is a member of the human T-cell leukaemia virus group. Nature. 1982 Nov 4;300(5887):63–66. doi: 10.1038/300063a0. [DOI] [PubMed] [Google Scholar]
- Popovic M., Sarin P. S., Robert-Gurroff M., Kalyanaraman V. S., Mann D., Minowada J., Gallo R. C. Isolation and transmission of human retrovirus (human t-cell leukemia virus). Science. 1983 Feb 18;219(4586):856–859. doi: 10.1126/science.6600519. [DOI] [PubMed] [Google Scholar]
- Reitz M. S., Jr, Popovic M., Haynes B. F., Clark S. C., Gallo R. C. Relatedness by nucleic acid hybridization of new isolates of human T-cell leukemia-lymphoma virus (HTLV) and demonstration of provirus in uncultured leukemic blood cells. Virology. 1983 Apr 30;126(2):688–672. doi: 10.1016/s0042-6822(83)80024-5. [DOI] [PubMed] [Google Scholar]
- Salahuddin S. Z., Markham P. D., Wong-Staal F., Franchini G., Kalyanaraman V. S., Gallo R. C. Restricted expression of human T-cell leukemia--lymphoma virus (HTLV) in transformed human umbilical cord blood lymphocytes. Virology. 1983 Aug;129(1):51–64. doi: 10.1016/0042-6822(83)90395-1. [DOI] [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]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Wong-Staal F., Hahn B., Manzari V., Colombini S., Franchini G., Gelmann E. P., Gallo R. C. A survey of human leukaemias for sequences of a human retrovirus. Nature. 1983 Apr 14;302(5909):626–628. doi: 10.1038/302626a0. [DOI] [PubMed] [Google Scholar]
- Yoshida M., Miyoshi I., Hinuma Y. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2031–2035. doi: 10.1073/pnas.79.6.2031. [DOI] [PMC free article] [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]
- Young H. A., Gonda M. A., De Feo D., Ellis R. W., Nagashima K., Scolnick E. M. Heteroduplex analysis of cloned rat endogenous replication-defective (30 S) retrovirus and Harvey murine sarcoma virus. Virology. 1980 Nov;107(1):89–99. doi: 10.1016/0042-6822(80)90275-5. [DOI] [PubMed] [Google Scholar]








