Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1994 Oct;68(10):6323–6331. doi: 10.1128/jvi.68.10.6323-6331.1994

Induction of antibody responses that neutralize human T-cell leukemia virus type I infection in vitro and in vivo by peptide immunization.

Y Tanaka 1, R Tanaka 1, E Terada 1, Y Koyanagi 1, N Miyano-Kurosaki 1, N Yamamoto 1, E Baba 1, M Nakamura 1, H Shida 1
PMCID: PMC237053  PMID: 8083972

Abstract

In order to define neutralization regions on the envelope antigen of human T-cell leukemia virus type I (HTLV-I), we have generated a number of new anti-envelope gp46 monoclonal antibodies from rats and mice. Epitopes recognized by new monoclonal antibodies which could neutralize HTLV-I in syncytium and transformation inhibition assays were localized to sequences in gp46 from amino acids 186 to 193, 190 to 195, 191 to 195, 191 to 196, and 194 to 199. Ovalbumin-conjugated synthetic gp46 peptides containing these neutralization epitopes, pep190-199 (a synthetic gp46 peptide containing amino acids 190 to 199) and pep180-204, but not pep185-194 or pep194-203, could give rise to HTLV-I-neutralizing antibody responses in rabbits. These immune or nonimmune rabbits were then challenged with HTLV-I by intravenous inoculation with 5 x 10(7) live HTLV-I-producing ILT-8M2 cells. By a PCR assay, it was revealed that HTLV-I provirus was detected in peripheral blood lymphocytes from nonimmune and pep288-312-immunized rabbits, whereas the provirus was not detected in peripheral blood lymphocytes from pep190-199- and pep180-204-immunized rabbits over an extended period. These results suggest that the induction of anti-gp46 neutralizing antibody responses by immunization with synthetic peptides has the potential to protect animals against HTLV-I infection in vivo.

Full text

PDF
6325

Images in this article

6329Image
on p.6329

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnon R. Synthetic peptides as the basis for vaccine design. Mol Immunol. 1991 Mar;28(3):209–215. doi: 10.1016/0161-5890(91)90063-p. [DOI] [PubMed] [Google Scholar]
  2. Baba E., Nakamura M., Tanaka Y., Kuroki M., Itoyama Y., Nakano S., Niho Y. Multiple neutralizing B-cell epitopes of human T-cell leukemia virus type 1 (HTLV-1) identified by human monoclonal antibodies. A basis for the design of an HTLV-1 peptide vaccine. J Immunol. 1993 Jul 15;151(2):1013–1024. [PubMed] [Google Scholar]
  3. Bartholomew C., Blattner W., Cleghorn F. Progression to AIDS in homosexual men co-infected with HIV and HTLV-I in Trinidad. Lancet. 1987 Dec 19;2(8573):1469–1469. doi: 10.1016/s0140-6736(87)91172-x. [DOI] [PubMed] [Google Scholar]
  4. Blattner W. A., Kalyanaraman V. S., Robert-Guroff M., Lister T. A., Galton D. A., Sarin P. S., Crawford M. H., Catovsky D., Greaves M., Gallo R. C. The human type-C retrovirus, HTLV, in Blacks from the Caribbean region, and relationship to adult T-cell leukemia/lymphoma. Int J Cancer. 1982 Sep 15;30(3):257–264. doi: 10.1002/ijc.2910300302. [DOI] [PubMed] [Google Scholar]
  5. De B. K., Lairmore M. D., Griffis K., Williams L. J., Villinger F., Quinn T. C., Brown C., Nzilambi, Sugimoto M., Araki S. Comparative analysis of nucleotide sequences of the partial envelope gene (5' domain) among human T lymphotropic virus type I (HTLV-I) isolates. Virology. 1991 May;182(1):413–419. doi: 10.1016/0042-6822(91)90692-5. [DOI] [PubMed] [Google Scholar]
  6. Desgranges C., Souche S., Vernant J. C., Smadja D., Vahlne A., Horal P. Identification of novel neutralization-inducing regions of the human T cell lymphotropic virus type I envelope glycoproteins with human HTLV-I-seropositive sera. AIDS Res Hum Retroviruses. 1994 Feb;10(2):163–173. doi: 10.1089/aid.1994.10.163. [DOI] [PubMed] [Google Scholar]
  7. Gessain A., Gout O. Chronic myelopathy associated with human T-lymphotropic virus type I (HTLV-I). Ann Intern Med. 1992 Dec 1;117(11):933–946. doi: 10.7326/0003-4819-117-11-933. [DOI] [PubMed] [Google Scholar]
  8. Hattori S., Kiyokawa T., Imagawa K., Shimizu F., Hashimura E., Seiki M., Yoshida M. Identification of gag and env gene products of human T-cell leukemia virus (HTLV). Virology. 1984 Jul 30;136(2):338–347. doi: 10.1016/0042-6822(84)90170-3. [DOI] [PubMed] [Google Scholar]
  9. Hino S., Yamaguchi K., Katamine S., Sugiyama H., Amagasaki T., Kinoshita K., Yoshida Y., Doi H., Tsuji Y., Miyamoto T. Mother-to-child transmission of human T-cell leukemia virus type-I. Jpn J Cancer Res. 1985 Jun;76(6):474–480. [PubMed] [Google Scholar]
  10. Hinuma Y., Nagata K., Hanaoka M., Nakai M., Matsumoto T., Kinoshita K. I., 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 Oct;78(10):6476–6480. doi: 10.1073/pnas.78.10.6476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hoshino H., Nakamura T., Tanaka Y., Miyoshi I., Yanagihara R. Functional conservation of the neutralizing domains on the external envelope glycoprotein of cosmopolitan and melanesian strains of human T cell leukemia/lymphoma virus type I. J Infect Dis. 1993 Dec;168(6):1368–1373. doi: 10.1093/infdis/168.6.1368. [DOI] [PubMed] [Google Scholar]
  12. Jacobson S., Raine C. S., Mingioli E. S., McFarlin D. E. Isolation of an HTLV-1-like retrovirus from patients with tropical spastic paraparesis. Nature. 1988 Feb 11;331(6156):540–543. doi: 10.1038/331540a0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Kannagi M., Kuroda M. J., Maeda Y., Harada S. Coexistence of fusion receptors for human T-cell leukemia virus type-I (HTLV-I) and human immunodeficiency virus type-1 (HIV-1) on MOLT-4 cells. Microbiol Immunol. 1991;35(9):729–740. doi: 10.1111/j.1348-0421.1991.tb01606.x. [DOI] [PubMed] [Google Scholar]
  15. Kaplan J. E., Osame M., Kubota H., Igata A., Nishitani H., Maeda Y., Khabbaz R. F., Janssen R. S. The risk of development of HTLV-I-associated myelopathy/tropical spastic paraparesis among persons infected with HTLV-I. J Acquir Immune Defic Syndr. 1990;3(11):1096–1101. [PubMed] [Google Scholar]
  16. Kataoka R., Takehara N., Iwahara Y., Sawada T., Ohtsuki Y., Dawei Y., Hoshino H., Miyoshi I. Transmission of HTLV-I by blood transfusion and its prevention by passive immunization in rabbits. Blood. 1990 Oct 15;76(8):1657–1661. [PubMed] [Google Scholar]
  17. Kinoshita K., Yamanouchi K., Ikeda S., Momita S., Amagasaki T., Soda H., Ichimaru M., Moriuchi R., Katamine S., Miyamoto T. Oral infection of a common marmoset with human T-cell leukemia virus type-I (HTLV-I) by inoculating fresh human milk of HTLV-I carrier mothers. Jpn J Cancer Res. 1985 Dec;76(12):1147–1153. [PubMed] [Google Scholar]
  18. Kiyokawa T., Yoshikura H., Hattori S., Seiki M., Yoshida M. Envelope proteins of human T-cell leukemia virus: expression in Escherichia coli and its application to studies of env gene functions. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6202–6206. doi: 10.1073/pnas.81.19.6202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kuroki M., Nakamura M., Itoyama Y., Tanaka Y., Shiraki H., Baba E., Esaki T., Tatsumoto T., Nagafuchi S., Nakano S. Identification of new epitopes recognized by human monoclonal antibodies with neutralizing and antibody-dependent cellular cytotoxicity activities specific for human T cell leukemia virus type 1. J Immunol. 1992 Aug 1;149(3):940–948. [PubMed] [Google Scholar]
  20. Kusuhara K., Sonoda S., Takahashi K., Tokugawa K., Fukushige J., Ueda K. Mother-to-child transmission of human T-cell leukemia virus type I (HTLV-I): a fifteen-year follow-up study in Okinawa, Japan. Int J Cancer. 1987 Dec 15;40(6):755–757. doi: 10.1002/ijc.2910400607. [DOI] [PubMed] [Google Scholar]
  21. Milich D. R. Synthetic T and B cell recognition sites: implications for vaccine development. Adv Immunol. 1989;45:195–282. doi: 10.1016/s0065-2776(08)60694-x. [DOI] [PubMed] [Google Scholar]
  22. Miyoshi I., Kubonishi I., Yoshimoto S., Shiraishi Y. A T-cell line derived from normal human cord leukocytes by co-culturing with human leukemic T-cells. Gan. 1981 Dec;72(6):978–981. [PubMed] [Google Scholar]
  23. Mueller N. The epidemiology of HTLV-I infection. Cancer Causes Control. 1991 Jan;2(1):37–52. doi: 10.1007/BF00052359. [DOI] [PubMed] [Google Scholar]
  24. Murphy E. L., Hanchard B., Figueroa J. P., Gibbs W. N., Lofters W. S., Campbell M., Goedert J. J., Blattner W. A. Modelling the risk of adult T-cell leukemia/lymphoma in persons infected with human T-lymphotropic virus type I. Int J Cancer. 1989 Feb 15;43(2):250–253. doi: 10.1002/ijc.2910430214. [DOI] [PubMed] [Google Scholar]
  25. Nakamura H., Hayami M., Ohta Y., Ishikawa K., Tsujimoto H., Kiyokawa T., Yoshida M., Sasagawa A., Honjo S. Protection of cynomolgus monkeys against infection by human T-cell leukemia virus type-I by immunization with viral env gene products produced in Escherichia coli. Int J Cancer. 1987 Sep 15;40(3):403–407. doi: 10.1002/ijc.2910400320. [DOI] [PubMed] [Google Scholar]
  26. Nakano S., Ando Y., Saito K., Moriyama I., Ichijo M., Toyama T., Sugamura K., Imai J., Hinuma Y. Primary infection of Japanese infants with adult T-cell leukaemia-associated retrovirus (ATLV): evidence for viral transmission from mothers to children. J Infect. 1986 May;12(3):205–212. doi: 10.1016/s0163-4453(86)94086-7. [DOI] [PubMed] [Google Scholar]
  27. Okochi K., Sato H., Hinuma Y. A retrospective study on transmission of adult T cell leukemia virus by blood transfusion: seroconversion in recipients. Vox Sang. 1984;46(5):245–253. doi: 10.1111/j.1423-0410.1984.tb00083.x. [DOI] [PubMed] [Google Scholar]
  28. 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 May 3;1(8488):1031–1032. doi: 10.1016/s0140-6736(86)91298-5. [DOI] [PubMed] [Google Scholar]
  29. Page J. B., Lai S. H., Chitwood D. D., Klimas N. G., Smith P. C., Fletcher M. A. HTLV-I/II seropositivity and death from AIDS among HIV-1 seropositive intravenous drug users. Lancet. 1990 Jun 16;335(8703):1439–1441. doi: 10.1016/0140-6736(90)91456-k. [DOI] [PubMed] [Google Scholar]
  30. Paine E., Garcia J., Philpott T. C., Shaw G., Ratner L. Limited sequence variation in human T-lymphotropic virus type 1 isolates from North American and African patients. Virology. 1991 May;182(1):111–123. doi: 10.1016/0042-6822(91)90654-t. [DOI] [PubMed] [Google Scholar]
  31. Palker T. J., Riggs E. R., Spragion D. E., Muir A. J., Scearce R. M., Randall R. R., McAdams M. W., McKnight A., Clapham P. R., Weiss R. A. Mapping of homologous, amino-terminal neutralizing regions of human T-cell lymphotropic virus type I and II gp46 envelope glycoproteins. J Virol. 1992 Oct;66(10):5879–5889. doi: 10.1128/jvi.66.10.5879-5889.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pique C., Pham D., Tursz T., Dokhélar M. C. Human T-cell leukemia virus type I envelope protein maturation process: requirements for syncytium formation. J Virol. 1992 Feb;66(2):906–913. doi: 10.1128/jvi.66.2.906-913.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Sahai Srivastava B. I., Minowada J. Terminal deoxynucleotidyl transferase activity in a cell line (molt-4) derived from the peripheral blood of a patient with acute lymphoblastic leukemia. Biochem Biophys Res Commun. 1973 Apr 2;51(3):529–535. doi: 10.1016/0006-291x(73)91346-6. [DOI] [PubMed] [Google Scholar]
  35. Schneider J., Yamamoto N., Hinuma Y., Hunsmann G. Sera from adult T-cell leukemia patients react with envelope and core polypeptides of adult T-cell leukemia virus. Virology. 1984 Jan 15;132(1):1–11. doi: 10.1016/0042-6822(84)90086-2. [DOI] [PubMed] [Google Scholar]
  36. Tajima K. The 4th nation-wide study of adult T-cell leukemia/lymphoma (ATL) in Japan: estimates of risk of ATL and its geographical and clinical features. The T- and B-cell Malignancy Study Group. Int J Cancer. 1990 Feb 15;45(2):237–243. doi: 10.1002/ijc.2910450206. [DOI] [PubMed] [Google Scholar]
  37. Tajima K., Tominaga S., Suchi T., Kawagoe T., Komoda H., Hinuma Y., Oda T., Fujita K. Epidemiological analysis of the distribution of antibody to adult T-cell leukemia-virus-associated antigen: possible horizontal transmission of adult T-cell leukemia virus. Gan. 1982 Dec;73(6):893–901. [PubMed] [Google Scholar]
  38. Takahashi K., Takezaki T., Oki T., Kawakami K., Yashiki S., Fujiyoshi T., Usuku K., Mueller N., Osame M., Miyata K. Inhibitory effect of maternal antibody on mother-to-child transmission of human T-lymphotropic virus type I. The Mother-to-Child Transmission Study Group. Int J Cancer. 1991 Nov 11;49(5):673–677. doi: 10.1002/ijc.2910490508. [DOI] [PubMed] [Google Scholar]
  39. Takehara N., Iwahara Y., Uemura Y., Sawada T., Ohtsuki Y., Iwai H., Hoshino H., Miyoshi I. Effect of immunization on HTLV-I infection in rabbits. Int J Cancer. 1989 Aug 15;44(2):332–336. doi: 10.1002/ijc.2910440224. [DOI] [PubMed] [Google Scholar]
  40. Tanaka Y., Isobe A., Masuda M., Tozawa H., Koyanagi Y., Yamamoto N., Shida H. Immunogenicity of human T cell leukemia virus type-I (HTLV-I) antigens for cytotoxic T lymphocytes in the rat system. J Immunol. 1991 Nov 15;147(10):3646–3652. [PubMed] [Google Scholar]
  41. Tanaka Y., Yasumoto M., Nyunoya H., Ogura T., Kikuchi M., Shimotohno K., Shiraki H., Kuroda N., Shida H., Tozawa H. Generation and characterization of monoclonal antibodies against multiple epitopes on the C-terminal half of envelope gp46 of human T-cell leukemia virus type-I (HTLV-I). Int J Cancer. 1990 Oct 15;46(4):675–681. doi: 10.1002/ijc.2910460421. [DOI] [PubMed] [Google Scholar]
  42. Tanaka Y., Zeng L., Shiraki H., Shida H., Tozawa H. Identification of a neutralization epitope on the envelope gp46 antigen of human T cell leukemia virus type I and induction of neutralizing antibody by peptide immunization. J Immunol. 1991 Jul 1;147(1):354–360. [PubMed] [Google Scholar]
  43. Weiss R. A., Clapham P., Nagy K., Hoshino H. Envelope properties of human T-cell leukemia viruses. Curr Top Microbiol Immunol. 1985;115:235–246. doi: 10.1007/978-3-642-70113-9_15. [DOI] [PubMed] [Google Scholar]
  44. 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]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES