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Vol. 52, No. 3, 2009
Issue release date: June 2009
Free Access
Intervirology 2009;52:115–122
(DOI:10.1159/000219384)

Proviral Loads and Clonal Expansion of HTLV-1-Infected Cells following Vertical Transmission: A 10-Year Follow-Up of Children in Jamaica

Umeki K.a · Hisada M.b · Maloney E.M.c · Hanchard B.d · Okayama A.a
aDepartment of Rheumatology, Infectious Diseases and Laboratory Medicine, University of Miyazaki, Miyazaki, Japan; bDivision of Cancer Epidemiology and Genetics, NCI, Rockville, Ind., and cCenters for Disease Control and Prevention, Atlanta, Ga., USA; dDepartment of Pathology, University of the West Indies, Mona, Jamaica
email Corresponding Author

Abstract

Objective: Few studies have specifically examined proviral load (PVL) and clonal evolution of human T-lymphotropic virus type 1 (HTLV-1)-infected cells in vertically infected children. Methods: Sequential samples (from ages 1 to 16 years) from 3 HTLV-1-infected children (cases A, B and C) in the Jamaica Mother Infant Cohort Study were analyzed for their PVL and clonal expansion of HTLV-1-infected cells in peripheral blood mononuclear cells (PBMCs) by inverse-long PCR. Results: The baseline PVL (per 100,000 PBMCs) of case A was 260 (at 1 year of age) and of case B it was 1,867 (at 3 years of age), and they remained constant for more than 10 years. Stochastic patterns of clonal expansion of HTLV-1-infected cells were predominately detected. In contrast, case C, who had lymphadenopathy, seborrheic dermatitis and hyperreflexia, showed an increase in PVL from 2,819 at 1.9 years to 13,358 at 13 years of age, and expansion of 2 dominant clones. Conclusion: The clonal expansion of HTLV-1-infected cells is induced in early childhood after infection acquired from their mothers. Youths with high PVL and any signs and symptoms associated with HTLV-1 infection should be closely monitored.


 goto top of outline Key Words

  • HTLV-1 infection
  • Clonal expansion, infected cells
  • Transmission, vertical

 goto top of outline Abstract

Objective: Few studies have specifically examined proviral load (PVL) and clonal evolution of human T-lymphotropic virus type 1 (HTLV-1)-infected cells in vertically infected children. Methods: Sequential samples (from ages 1 to 16 years) from 3 HTLV-1-infected children (cases A, B and C) in the Jamaica Mother Infant Cohort Study were analyzed for their PVL and clonal expansion of HTLV-1-infected cells in peripheral blood mononuclear cells (PBMCs) by inverse-long PCR. Results: The baseline PVL (per 100,000 PBMCs) of case A was 260 (at 1 year of age) and of case B it was 1,867 (at 3 years of age), and they remained constant for more than 10 years. Stochastic patterns of clonal expansion of HTLV-1-infected cells were predominately detected. In contrast, case C, who had lymphadenopathy, seborrheic dermatitis and hyperreflexia, showed an increase in PVL from 2,819 at 1.9 years to 13,358 at 13 years of age, and expansion of 2 dominant clones. Conclusion: The clonal expansion of HTLV-1-infected cells is induced in early childhood after infection acquired from their mothers. Youths with high PVL and any signs and symptoms associated with HTLV-1 infection should be closely monitored.

Copyright © 2009 S. Karger AG, Basel


 goto top of outline References
  1. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H: Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood 1977;50:481–492.
  2. Yoshida M, Miyoshi I, Hinuma Y: Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its imolication in the disease. Proc Natl Acad Sci USA 1982;79:2031–2035.
  3. Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, Matsumoto M, Tara M: HTLV-I associated myelopathy, a new clinical entity. Lancet 1986;1:1031–1032.
  4. Arisawa K, Soda M, Endo S, Kurokawa K, Katamine S, Shimokawa I, Koba T, Takahashi T, Saito H, Doi H, Shirahama S: Evaluation of adult T-cell leukemia/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern Japan. Int J Cancer 2000;85:319–324.
  5. Yamaguchi K, Watanabe T: Human T lymphotropic virus type-I and adult T-cell leukemia in Japan. Int J Hematol 2002;76:240–245.
  6. 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;57:4862–4867.
  7. Etoh K, Yamaguchi K, Tokudome S, Watanabe T, Okayama A, Stuver S, Mueller N, Takatsuki K, Matsuoka M: Rapid quantification of HTLV-I provirus load: detection of monoclonal proliferation of HTLV-I-infected cells among blood donors. Int J Cancer 1999;81:856–864.

    External Resources

  8. Okayama A, Stuver S, Iga M, Okamoto M, Mueller N, Matsuoka M, Yamaguchi K, Tachibana N, Tsubouchi H: Sequential change of virus markers in seroconverters with community-acquired infection of human T lymphotropic virus type I. J Infect Dis 2001;183:1031–1037.
  9. Wilks R, Hanchard B, Morgan O, Williams E, Cranston B, Smith ML, Rodgers-Johnson P, Manns A: Patterns of HTLV-I infection among family members of patients with adult T-cell leukemia/lymphoma and HTLV-I associated myelopathy/tropical spastic paraparesis. Int J Cancer 1996;65:272–273.
  10. Bartholomew C, Jack N, Edwards J, Charles W, Corbin D, Cleghorn FR, Blattner WA: HTLV-I serostatus of mothers of patients with adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. J Hum Virol 1998;1:302–305.
  11. Maloney EM, Yamano Y, Vanveldhuisen PC, Sawada T, Kim N, Cranston B, Hanchard B, Jacobson S, Hisada M: Natural history of viral markers in children infected with human T lymphotropic virus type I in Jamaica. J Infect Dis 2006;194:552–560.
  12. LaGrenade L, Hanchard B, Fletcher V, Cranston B, Blattner W: Infective dermatitis of Jamaican children: a marker for HTLV-I infection. Lancet 1990;336:1345–1347.
  13. Maloney EM, Nagai M, Hisada M, Soldan SS, Goebel PB, Carrington M, Sawada T, Brennan MB, Cranston B, Hanchard B, Jacobson S: Prediagnostic human T lymphotropic virus type I provirus loads were highest in Jamaican children who developed seborrheic dermatitis and severe anemia. J Infect Dis 2004;189:41–45.
  14. Maloney EM, Wiktor SZ, Palmer P, Cranston B, Pate EJ, Cohn S, Kim N, Miley W, Thomas TL, Blattner WA, Hanchard B: A cohort study of health effects of human T-cell lymphotropic virus type I infection in Jamaican children. Pediatrics 2003;112:e136–e142.
  15. Hanchard B, LaGrenade L, Carberry C, Fletcher V, Williams E, Cranston B, Blattner WA, Manns A: Childhood infective dermatitis evolving into adult T-cell leukaemia after 17 years. Lancet 1991;338:1593–1594.
  16. La Grenade L: HTLV-I-associated infective dermatitis: past, present, and future. J Acquir Immune Defic Syndr Hum Retrovirol 1996;13(suppl 1):S46–S49.
  17. Yoshida M: Multiple viral strategies of HTLV-1 for dysregulation of cell growth control. Annu Rev Immunol 2001;19:475–496.
  18. Okayama A, Stuver S, Matsuoka M, Ishizaki J, Tanaka G, Kubuki Y, Mueller N, Hsieh CC, Tachibana N, Tsubouchi H: Role of HTLV-1 proviral DNA load and clonality in the development of adult T-cell leukemia/lymphoma in asymptomatic carriers. Int J Cancer 2004;110:621–625.
  19. Cavrois M, Leclercq I, Gout O, Gessain A, Wain-Hobson S, Wattel E: Persistent oligoclonal expansion of human T-cell leukemia virus type 1-infected circulating cells in patients with tropical spastic paraparesis/HTLV-1 associated myelopathy. Oncogene 1998;17:77–82.
  20. Wiktor SZ, Pate EJ, Rosenberg PS, Barnett M, Palmer P, Medeiros D, Maloney EM, Blattner WA: Mother-to-child transmission of human T-cell lymphotropic virus type I associated with prolonged breast-feeding. J Hum Virol 1997;1:37–44.
  21. Sambrook J, Russell DW: Molecular cloning: a laboratory manual, 3rd ed. New York, Cold Spring Harbor Laboratory Press, 2001, pp 6.4–11p.
  22. 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 USA 1983;80:3618–3622.
  23. Benhattar J, Delacretaz F, Martin P, Chaubert P, Costa J: Improved polymerase chain reaction detection of clonal T-cell lymphoid neoplasms. Diagn Mol Pathol 1995;4:108–112.
  24. Gabet AS, Kazanji M, Couppie P, Clity E, Pouliquen JF, Sainte-Marie D, Aznar C, Wattel E: Adult T-cell leukaemia/lymphoma-like human T-cell leukaemia virus-1 replication in infective dermatitis. Br J Haematol 2003;123:406–412.
  25. Tanaka G, Okayama A, Watanabe T, Aizawa S, Stuver S, Mueller N, Hsieh CC, Tsubouchi H: The clonal expansion of human T lymphotropic virus type 1-infected T cells: a comparison between seroconverters and long-term carriers. J Infect Dis 2005;191:1140–1147.
  26. Ozawa T, Itoyama T, Sadamori N, Yamada Y, Hata T, Tomonaga M, Isobe M: Rapid isolation of viral integration site reveals frequent integration of HTLV-1 into expressed loci. J Hum Genet 2004;49:154–165.
  27. Hanai S, Nitta T, Shoda M, Tanaka M, Iso N, Mizoguchi I, Yashiki S, Sonida S: Integration of human T-cell leukemia virus type 1 in genes of leukemia cells of patients with adult T-cell leukemia. Cancer Sci 2004;95:306–310.
  28. Plumelle Y, Gonin C, Edouard A, Bucher BJ, Thomas L, Brebion A, Panelatti G: Effect of Strongyloides stercoralis infection and eosinophilia on age at onset and prognosis of adult T-cell leukemia. Am J Clin Pathol 1997;107:81–87.
  29. Farre L, de Oliveira Mde F, Primo J, Vandamme AM, Van Weyenbergh J, Bittencourt AL: Early sequential development of infective dermatitis, human T cell lymphotropic virus type 1-associated myelopathy, and adult T cell leukemia/lymphoma. Clin Infect Dis 2008;46:440–442.

 goto top of outline Author Contacts

Akihiko Okayama, MD, PhD
Department of Rheumatology, Infectious Diseases and Laboratory Medicine
Faculty of Medicine, University of Miyazaki
5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)
Tel. +81 985 7284, Fax +81 985 85 4709, E-Mail okayama@med.miyazaki-u.ac.jp


 goto top of outline Article Information

Received: August 20, 2008
Accepted: March 25, 2009
Published online: May 20, 2009
Number of Print Pages : 8
Number of Figures : 5, Number of Tables : 1, Number of References : 29


 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)

Vol. 52, No. 3, Year 2009 (Cover Date: June 2009)

Journal Editor: Liebert U.G. (Leipzig)
ISSN: 0300-5526 (Print), eISSN: 1423-0100 (Online)

For additional information: http://www.karger.com/INT


Copyright / Drug Dosage / Disclaimer

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.
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.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Objective: Few studies have specifically examined proviral load (PVL) and clonal evolution of human T-lymphotropic virus type 1 (HTLV-1)-infected cells in vertically infected children. Methods: Sequential samples (from ages 1 to 16 years) from 3 HTLV-1-infected children (cases A, B and C) in the Jamaica Mother Infant Cohort Study were analyzed for their PVL and clonal expansion of HTLV-1-infected cells in peripheral blood mononuclear cells (PBMCs) by inverse-long PCR. Results: The baseline PVL (per 100,000 PBMCs) of case A was 260 (at 1 year of age) and of case B it was 1,867 (at 3 years of age), and they remained constant for more than 10 years. Stochastic patterns of clonal expansion of HTLV-1-infected cells were predominately detected. In contrast, case C, who had lymphadenopathy, seborrheic dermatitis and hyperreflexia, showed an increase in PVL from 2,819 at 1.9 years to 13,358 at 13 years of age, and expansion of 2 dominant clones. Conclusion: The clonal expansion of HTLV-1-infected cells is induced in early childhood after infection acquired from their mothers. Youths with high PVL and any signs and symptoms associated with HTLV-1 infection should be closely monitored.



 goto top of outline Author Contacts

Akihiko Okayama, MD, PhD
Department of Rheumatology, Infectious Diseases and Laboratory Medicine
Faculty of Medicine, University of Miyazaki
5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)
Tel. +81 985 7284, Fax +81 985 85 4709, E-Mail okayama@med.miyazaki-u.ac.jp


 goto top of outline Article Information

Received: August 20, 2008
Accepted: March 25, 2009
Published online: May 20, 2009
Number of Print Pages : 8
Number of Figures : 5, Number of Tables : 1, Number of References : 29


 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)

Vol. 52, No. 3, Year 2009 (Cover Date: June 2009)

Journal Editor: Liebert U.G. (Leipzig)
ISSN: 0300-5526 (Print), eISSN: 1423-0100 (Online)

For additional information: http://www.karger.com/INT


Copyright / Drug Dosage

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.
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.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H: Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood 1977;50:481–492.
  2. Yoshida M, Miyoshi I, Hinuma Y: Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its imolication in the disease. Proc Natl Acad Sci USA 1982;79:2031–2035.
  3. Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, Matsumoto M, Tara M: HTLV-I associated myelopathy, a new clinical entity. Lancet 1986;1:1031–1032.
  4. Arisawa K, Soda M, Endo S, Kurokawa K, Katamine S, Shimokawa I, Koba T, Takahashi T, Saito H, Doi H, Shirahama S: Evaluation of adult T-cell leukemia/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern Japan. Int J Cancer 2000;85:319–324.
  5. Yamaguchi K, Watanabe T: Human T lymphotropic virus type-I and adult T-cell leukemia in Japan. Int J Hematol 2002;76:240–245.
  6. 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;57:4862–4867.
  7. Etoh K, Yamaguchi K, Tokudome S, Watanabe T, Okayama A, Stuver S, Mueller N, Takatsuki K, Matsuoka M: Rapid quantification of HTLV-I provirus load: detection of monoclonal proliferation of HTLV-I-infected cells among blood donors. Int J Cancer 1999;81:856–864.

    External Resources

  8. Okayama A, Stuver S, Iga M, Okamoto M, Mueller N, Matsuoka M, Yamaguchi K, Tachibana N, Tsubouchi H: Sequential change of virus markers in seroconverters with community-acquired infection of human T lymphotropic virus type I. J Infect Dis 2001;183:1031–1037.
  9. Wilks R, Hanchard B, Morgan O, Williams E, Cranston B, Smith ML, Rodgers-Johnson P, Manns A: Patterns of HTLV-I infection among family members of patients with adult T-cell leukemia/lymphoma and HTLV-I associated myelopathy/tropical spastic paraparesis. Int J Cancer 1996;65:272–273.
  10. Bartholomew C, Jack N, Edwards J, Charles W, Corbin D, Cleghorn FR, Blattner WA: HTLV-I serostatus of mothers of patients with adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. J Hum Virol 1998;1:302–305.
  11. Maloney EM, Yamano Y, Vanveldhuisen PC, Sawada T, Kim N, Cranston B, Hanchard B, Jacobson S, Hisada M: Natural history of viral markers in children infected with human T lymphotropic virus type I in Jamaica. J Infect Dis 2006;194:552–560.
  12. LaGrenade L, Hanchard B, Fletcher V, Cranston B, Blattner W: Infective dermatitis of Jamaican children: a marker for HTLV-I infection. Lancet 1990;336:1345–1347.
  13. Maloney EM, Nagai M, Hisada M, Soldan SS, Goebel PB, Carrington M, Sawada T, Brennan MB, Cranston B, Hanchard B, Jacobson S: Prediagnostic human T lymphotropic virus type I provirus loads were highest in Jamaican children who developed seborrheic dermatitis and severe anemia. J Infect Dis 2004;189:41–45.
  14. Maloney EM, Wiktor SZ, Palmer P, Cranston B, Pate EJ, Cohn S, Kim N, Miley W, Thomas TL, Blattner WA, Hanchard B: A cohort study of health effects of human T-cell lymphotropic virus type I infection in Jamaican children. Pediatrics 2003;112:e136–e142.
  15. Hanchard B, LaGrenade L, Carberry C, Fletcher V, Williams E, Cranston B, Blattner WA, Manns A: Childhood infective dermatitis evolving into adult T-cell leukaemia after 17 years. Lancet 1991;338:1593–1594.
  16. La Grenade L: HTLV-I-associated infective dermatitis: past, present, and future. J Acquir Immune Defic Syndr Hum Retrovirol 1996;13(suppl 1):S46–S49.
  17. Yoshida M: Multiple viral strategies of HTLV-1 for dysregulation of cell growth control. Annu Rev Immunol 2001;19:475–496.
  18. Okayama A, Stuver S, Matsuoka M, Ishizaki J, Tanaka G, Kubuki Y, Mueller N, Hsieh CC, Tachibana N, Tsubouchi H: Role of HTLV-1 proviral DNA load and clonality in the development of adult T-cell leukemia/lymphoma in asymptomatic carriers. Int J Cancer 2004;110:621–625.
  19. Cavrois M, Leclercq I, Gout O, Gessain A, Wain-Hobson S, Wattel E: Persistent oligoclonal expansion of human T-cell leukemia virus type 1-infected circulating cells in patients with tropical spastic paraparesis/HTLV-1 associated myelopathy. Oncogene 1998;17:77–82.
  20. Wiktor SZ, Pate EJ, Rosenberg PS, Barnett M, Palmer P, Medeiros D, Maloney EM, Blattner WA: Mother-to-child transmission of human T-cell lymphotropic virus type I associated with prolonged breast-feeding. J Hum Virol 1997;1:37–44.
  21. Sambrook J, Russell DW: Molecular cloning: a laboratory manual, 3rd ed. New York, Cold Spring Harbor Laboratory Press, 2001, pp 6.4–11p.
  22. 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 USA 1983;80:3618–3622.
  23. Benhattar J, Delacretaz F, Martin P, Chaubert P, Costa J: Improved polymerase chain reaction detection of clonal T-cell lymphoid neoplasms. Diagn Mol Pathol 1995;4:108–112.
  24. Gabet AS, Kazanji M, Couppie P, Clity E, Pouliquen JF, Sainte-Marie D, Aznar C, Wattel E: Adult T-cell leukaemia/lymphoma-like human T-cell leukaemia virus-1 replication in infective dermatitis. Br J Haematol 2003;123:406–412.
  25. Tanaka G, Okayama A, Watanabe T, Aizawa S, Stuver S, Mueller N, Hsieh CC, Tsubouchi H: The clonal expansion of human T lymphotropic virus type 1-infected T cells: a comparison between seroconverters and long-term carriers. J Infect Dis 2005;191:1140–1147.
  26. Ozawa T, Itoyama T, Sadamori N, Yamada Y, Hata T, Tomonaga M, Isobe M: Rapid isolation of viral integration site reveals frequent integration of HTLV-1 into expressed loci. J Hum Genet 2004;49:154–165.
  27. Hanai S, Nitta T, Shoda M, Tanaka M, Iso N, Mizoguchi I, Yashiki S, Sonida S: Integration of human T-cell leukemia virus type 1 in genes of leukemia cells of patients with adult T-cell leukemia. Cancer Sci 2004;95:306–310.
  28. Plumelle Y, Gonin C, Edouard A, Bucher BJ, Thomas L, Brebion A, Panelatti G: Effect of Strongyloides stercoralis infection and eosinophilia on age at onset and prognosis of adult T-cell leukemia. Am J Clin Pathol 1997;107:81–87.
  29. Farre L, de Oliveira Mde F, Primo J, Vandamme AM, Van Weyenbergh J, Bittencourt AL: Early sequential development of infective dermatitis, human T cell lymphotropic virus type 1-associated myelopathy, and adult T cell leukemia/lymphoma. Clin Infect Dis 2008;46:440–442.