Original Paper
Mycosis fungoides in European Russia: No Antibodies to Human T Cell Leukemia Virus Type I Structural Proteins, but Virus-Like Sequences in Blood and Saliva
Vladimir A. Morozova, b, Alexander V. Syrtsevb, Heinz Ellerbroka, Elena V. Nikolaevac, Andrei S. Bavykinb, Georg Paulia
aRetrovirology, Robert Koch-Institut, Berlin, Germany; bN.N. Blokhin Cancer Research Center RAMS, and cM.F. Vladimirsky Moscow Region Clinical Institute, Moscow, Russia
Address of Corresponding Author
Intervirology 2005;48:362-371 (DOI: 10.1159/000086063)
Key Words
- Mycosis fungoides
- European Russia
- Human T cell leukemia virus
- tax sequences
- Antibodies
Abstract
Objective: Mycosis fungoides (MF) is the most frequent form of cutaneous T cell lymphoma (CTCL). Human T cell leukemia virus type 1 (HTLV-1) involvement in MF progression is a matter of debate. The goal of the investigation was to search for HTLV-1 markers in a group of MF patients from a nonendemic area to HTLV-1. Materials and Methods: Fifty MF patients and 60 healthy donors from Moscow and the Moscow region were examined for HTLV-1 markers by Western blot, PCR, nested PCR, PCR/Southern hybridization, TaqMan real-time PCR and sequencing. Results: Plasma samples from MF patients were repeatedly negative for antibodies to HTLV-1 structural proteins. HTLV-1 tax-related sequences (corresponding to the second exon) were found in blood from 20 of 50 MF patients and in 3 of 5 saliva specimens. Three of 8 sequenced tax-like amplimers were identical and 5 of 8 contained 1-2 substitutions. tax transcripts and antibodies to p40tax were detected in some 'PCR-tax'-positive MF patients. Defective HTLV-1 genomes were demonstrated in 2 of 50 MF patients. Phylogenetic analysis of the defective genome 5'-LTR sequence revealed a relationship with HTLV-1a sequences from the transcontinental subgroup of HTLV-1. Conclusions: HTLV-1 tax-like sequences were revealed in blood and for the first time in saliva from MF patients living in an HTLV-1 nonendemic region. Expression of tax-like sequences was confirmed by both reverse transcription PCR and Western blot. Copyright © 2005 S. Karger AG, Basel
References
- 1.
- Poiesz B, Ruscetti F, Gazdar A, Bunn P, Minna J, Gallo R: 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 USA 1980;77:7415-7419.

- 2.
- Hinuma Y, Nagata K, Hanaoka M, Nakai T, Matsumoto K, Kinoshita S, Shirakava 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 USA 1981;78:6476-6480.

- 3.
- Gessain A, Barin F, Vernant J, Gout O, Maurs L, Calender A, de Thé G: Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet 1985;ii:407-409.

- 4.
- Osame M, Usaku K, Izumo S, Izichi N, Amitani H, Igata A, Matsumoto M, Tara M: HTLV-I associated myelopathy, a new clinical entity. Lancet 1986;i:1031-1032.

- 5.
- Blattner W: Epidemiology of HTLV-1 and associated diseases; in Blattner W (ed): Human Retrovirology HTLV. New York, Raven Press, 1990, pp 251-264.
- 6.
- Merle H, Cabre P, Merle S, Smadja D: Ocular lesions in 200 patients infected by the human T-cell lymphotropic virus type 1 in Martinique (French West Indies). Am J Ophthalmol 2002;134:190-195.

- 7.
- Miyoshi I, Sawada T, Iwahara S, Ishii K, Kubonishi I, Tguchi H: Excretion of HTLV-1 in saliva. JAMA 1992;267:236.

- 8.
- Yamamoto T, Terada K, Nishida N, Moriuchi R, Shirabe S, Nakamura T, Tsuji Y, Miyamoto T, Katamine S: Inhibitory activity in saliva of cell-to-cell transmission of human T-cell lymphotropic virus type 1 in vitro: Evaluation of saliva as an alternative source of transmission. J Clin Microbiol 1995;33:1510-1515.

- 9.
- Achiron A, Pinhas-Hameil O, Barkak Y, Doll L, Offen D, Djaldetti R, Frankel G, Shohat B: Detection of proviral human T-cell lymphotropic virus type I DNA in mouthwash samples of HAM/TSP and HTLV-I carriers. Arch Virol 1996;14:147-153.

- 10.
- Al B, Visser S, Hoek A, Doornum G, Coutinho R, Huisman H: Incident of HTLV-I/II infection in seronegative high-risk individuals. J Med Virol 1993;39:260-265.

- 11.
- Saito S, Ando Y, Furuki K, Kakimoto K, TanigawaT, Moriyama I, Ichijo M, Nakamura M, Otani K, Sugamura K: Detection of HTLV-1 genome in seronegative infants born to HTLV-1 seropositive mothers by PCR. Jpn J Cancer Res 1989;80:808-812.

- 12.
- Kubota K, Ikezoe T, Hakoda E, Sawada T, Taguchi H, Mioschi I: HTLV-I-seronegative, genome-positive adult T-cell leukemia: Report of a case. Am J Hematol 1996;53:133-136.

- 13.
- Vandamme A, Laethem K, Liu H, Brussel M, Delaporte E, Costa C, Fleischer C, Taylor G, Bertazonni U, Desmyter J, Goubau P: Use of generic polymerase chain reaction assay detecting human T-lymphotropic virus (HTLV) types I, II and divergent simian strain in the evolution of individuals with indeterminate HTLV serology. J Med Virol 1997;52:1-7.

- 14.
- Ramirez E, Cartier L, Rios M, Fernandez J: Defective HTLV-I provirus in 10 Chilean seronegative patients with tropical spastic paraparesis or HTLV-1-associated myelopathy.J Clin Microbiol 1998;36:1811-1813.
- 15.
- Ratner L, Philpott T, Trowbridge D: Nucleotide sequence analysis of isolate of human T-lymphotropic virus type 1 of diverse geographical origins. AIDS Res Hum Retroviruses 1991;7:923-941.

- 16.
- Gessain A, Boeri E, Yanagichara R, Gallo R, Franchini G: Complete nucleotide sequence of a highly divergent human T-cell leukemia (lymphotropic) virus type 1 (HTLV-1) variant from Melanesia: Genetic and phylogenetic relationship to HTLV-1 strains from other geographical regions. J Virol 1993;67:1015-1023.

- 17.
- Mahieux R, Ibrahim F, Mauclere P, Herve V, Michel P, Takaia F, Chappey C, Garin B, Van der Ryst E, Guillemain B, Ledru E, Delaporte E, et al: Molecular epidemiology of 58 new African human T-cell leukemia virus type 1 (HTLV-1) strains: Identification of a new and distinct HTLV-1 molecular subtype in Central Africa and in Pygmies. J Virol 1997;71:1317-1333.

- 18.
- Orita S, Kabayashi H, Aono Y, Saiga A, Marda M, Igarashi H: p21X mRNA is expressed as a single spliced pX transcript from defective provirus having a partial deletion of the pol-env region in human T-cell leukemia virus type 1-infected cells. Nucleic Acids Res 1993;21:3799-3807.

- 19.
- Morozov VA, Lagaye S, Taylor G, Matutes E, Weiss RA: Chimeric matrix proteins encoded by defective proviruses with large internal deletions in human T-cell leukemia virus type-1 infected humans. J Virol 2000;74:3933-3940.

- 20.
- Hill S, Shuh M, Derse D: Comparisons of defective HTLV-I proviruses predict the mode of origin and coding potential of internally deleted genomes. Virology 1999;263:273-281.

- 21.
- Girardi M, Healder PW, Wilson LD: The pathogenesis of mycosis fungoides. N Engl J Med 2004;350:1978-1988.

- 22.
- Anonymous: Acquired immunodeficiency syndrome (AIDS): Proposed WHO criteria for interpreting results from Western-blot assays for HIV, HIV-II and HTLV-I/HTLV-II. Weekly Epidemic Res 1990;65:281-283.
- 23.
- Yoshida M: Multiply viral strategies of HTLV-1 for dysregulation of cell growth control. Ann Rev Immunol 2001;19:475-496.

- 24.
- Pancake BA, Zucker-Franklin D, Coutavas EE: The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell lymphotropic virus-associated disease. J Clin Invest 1995;95:547-554.

- 25.
- Pancake BA, Zucker-Franklin D: The difficulty of detecting HTLV-1 proviral sequences in patients with mycosis fungoides. J Acquir Immune Defic Syndr Hum Retrovirol 1996;13:314-319.

- 26.
- Ghosh SK, Abrams JT, Terunuma H, Vonderheid EC, DeFreitas E: Human T-cell leukemia virus type 1 tax/rex DNA and RNA in cutaneous T-cell lymphoma. Blood 1994;84:2663-2671.

- 27.
- Zucker-Franklin D, Pancake BA, Lalezari P, Khorshidi M: Transmission of human T-cell lymphotropic virus type I tax to rabbits by tax-only-positive human cells. Clin Diagn Lab Immunol 2000;7:274-278.

- 28.
- Zucker-Franklin D: The role of human T-cell lymphotropic virus type I tax in the development of cutaneous T cell lymphoma. Ann NY Acad Sci 2001;941:86-96.

- 29.
- Hall W, Liu C, Schneewind O, Takahashi H, Kaplan M, Roupe G, Vahlne A: Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides. Science 1991;253:317-320.

- 30.
- Whittaker SJ, Luzzatto L: HTLV-1 provirus and mycosis fungoides. Science 1993;259:1470.

- 31.
- Cowan EP, Nemo GJ, Williams AE, Alexander RK, Vallejo A, Hewlett IK, Lal RB, Dezzutti CS, Gallahan D, George K, Pancake BA, Zucker-Franklin D, McCurdy PR, Tabor E: Absence of human T-lymphotropic virus type I tax sequences in a population of normal blood donors in the Baltimore, MD/Washington, DC, area: Results from a multicenter study. Transfusion 1999;39:904-909.

- 32.
- Dezzutti CS, Guenthner PC, Daniel S, Utz U, Cabrera T, Marshall JH, Bianco C, Lal RB, Cowan EP: Detection of human T-lymphotropic virus (HTLV) tax sequences in New York City blood donors seronegative for HTLV types 1 and 2. Clin Diagn Lab Immunol 2003;10:715-717.

- 33.
- Zucker-Franklin D, Pancake BA, Najfeld V: Localization of HTLV-1 tax proviral DNA in mononuclear cells. Blood Cells Mol Dis 2003;31:1-6.

- 34.
- Gurtsevitch V, Senyuta N, Pavlish O, Shich J, Pivnik A, Yakovleva L, Stepina V, Kremenetckaya A, Syrtsev A, Chukanov S, Lee H: Clinical, morphological and virological features of HTLV-I positive case of ATL in white man from Caucasus. Leukemia Res 1993;17:621-627.

- 35.
- Morozov VA, Weiss RA: Two types of HTLV-I particles are released from MT-2 cells. Virology 1999;255:279-284.

- 36.
- Kwok S, Ehrlich G, Poiesz B, Kalish R, Sninsky JJ: Enzymatic amplification of HTLV-1 viral sequences from peripheral blood mononuclear cells and infected tissues. Blood 1988;72:1117-1123.

- 37.
- Heid A, Stevens J, Livak K, Williams P: Real time quantitative PCR. Genome Res 1996;6:986-994.

- 38.
- Higgins D, Sharp P: Fast and sensitive multiple sequence alignments on a microcomputer. Comput Appl Biosci 1989;5:151-153.

- 39.
- Kimura M: A simple method for estimating evolutionary rates of base substitution through comparative studies of nucleotide sequences. J Mol Evol 1980;16:111-120.

- 40.
- Saitou N, Nei M: The neighbor-joining method: A new method for reconstructing phylogenetic trees. Mol Biol Evol 1987;4:406-425.

- 41.
- Felsenstein J: Confidence limits on phylogenies: An approach using the bootstrap. Evolution 1985;39:783-791.

- 42.
- Van Dooren S, Gotuzzo E, Salemi M, Watts D, Audenaert E, Duwe S, Ellerbrok H, Grassmann R, Hagelberg E, Vandamme AM: Evidence for post-Columbian introduction of human T-cell lymphotropic virus in Latin America. J Gen Virol 1998;79:2695-2708.

- 43.
- Yamashita M, Picchio G, Veronesi R, Ohkura S, Bare P, Hayami M: HTLV-Is in Argentina are phylogenetically similar to those of other South American countries, but different from HTLV-1s in Africa. J Med Virol 1998;55:152-160.

- 44.
- Senyuta N, Syrtsev A, Yamashita M, Stepina V, Susova O, Scherbak L, Pavlish O, Hayami M, Gurtsevitch V: Sero-epidemiologic and phylogenetic studies of HTLV-1 infection in two countries of the Caspian sea region. Int J Cancer 1998;77:488-493.

- 45.
- Ellerbrok H, Fleischer C, Salemi M, Renhardt P, Ludwig WD, Vandamme AM, Pauli G: Sequence analysis of the first HTLV-1 infection in Germany without relations to endemic areas. AIDS Res Hum Retroviruses 1998;14:1199-1203.

- 46.
- Syrtsev A, Yamashita M, Senyuta N, Susova O, Hayami M, Gurtsevitch V: HTLV-1 infection among Nivkhi people in Sakhalin: Comparative serologic and phylogenetic analyses for 9 years. Int J Cancer 2000;87:379-381.

- 47.
- Zucker-Franklin D, Pancake BA, Marmor M, Leglier P: Reexamination of human T cell lymphotropic virus (HTLV-I/II) prevalence. Proc Natl Acad Sci USA 1997;94:6403-6407.

- 48.
- Shohat M, Hodak E, Hannig H, Bodemer W, David M, Shochat B: Evidence for the cofactor role of human T-cell lymphotropic virus type 1 in mycosis fungoides and Sezary syndrome. Br J Dermatol 1999;141:44-49.

- 49.
- Manca N, Perandin F, De Simone N, Giannini F, Bonifati D, Angelini C: Detection of HTLV-I tax-rex and pol gene sequences of thymus gland in a large group of patients with myasthenia gravis. J Acquir Immune Defic Syndr 2002;29:300-306.

- 50.
- Detmar M, Pauli G, Anagnostopoulos I, Wunderlich U, Herbst H, Garbe C, Stein H: A case of classical mycosis fungoides associated with human T-cell lymphotropic virus type I. Br J Dermatol 1991;124:198-202.

- 51.
- Manca N, Piacentini E, Gelmi M, Calzavara P, Manganoni A, Glukhov A, Gargiulo F, Francesco M, Pirali F, Panfilis G, Turano A: Persistence of human T cell lymphotrophic virus type 1 (HTLV-1) sequences in peripheral blood mononuclear cell from patients with mycosis fungoides. J Exp Med 1994;180:1973-1978.

- 52.
- el-Farrash MA, Salem HA, Kuroda MJ, Morizono K, Kannagi M, Harada S: Isolation of human T-cell leukemia virus type 1 from a transformed T-cell line derived spontaneously from lymphocytes of a seronegative Egyptian patient with mycosis fungoides. Blood 1995;86:1842-1849.

- 53.
- Bazarbachi A, Soriano V, Pawson R, Vallejo A, Moudgil T, Matutes E, Peries J, Molina A, de The H, Schulz TF, Catovsky D, Gill PS: Mycosis fungoides and Sezary syndrome are not associated with HTLV-I infection: An international study. Br J Haematol 1997;98:927-933.

- 54.
- Wood GS, Schaffer JM, Boni R, Dummer R, Burg G, Takeshita M, Kikuchi M: No evidence of HTLV-1 proviral integration in lymphoproliferative disorders associated with cutaneous T-cell lymphoma. Am J Pathol 1997;150:667-673.

Author Contacts
Dr. Vladimir Morozov, PhD Retrovirology, Robert Koch-Institut Nordufer 20 DE-13353 Berlin (Germany) Tel. +49 30 45472508, Fax +49 30 45472605, E-Mail Morvlad@hotmail.com
Article Information
Received: July 29, 2004
Accepted after revision: December 7, 2004
Number of Print Pages : 10
Number of Figures : 5, Number of Tables : 0, Number of References : 54
Publication Details
Intervirology (International Journal of Basic and Medical Virology)
Vol. 48, No. 6, Year 2005 (Cover Date: November-December 2005)
Journal Editor: Liebert, U.G. (Leipzig)
ISSN: 0300-5526 (print), 1423-0100 (Online) For additional information: http://www.karger.com/int
Drug Dosage / Copyright
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center. |
|
|