Evolution of mutation rate and virulence among human retroviruses

  • Paul W. Ewald


High mutation rates are generally considered to be detrimental to the fitness of multicellular organisms because mutations untune finely tuned biological machinery. However, high mutation rates may be favoured by a need to evade an immune system that has been strongly stimulated to recognize those variants that reproduced earlier during the infection, HIV infections conform to this situation because they are characterized by large numbers of viruses that are continually breaking latency and large numbers that are actively replicating throughout a long period of infection. To be transmitted, HIVS are thus generally exposed to an immune system that has been activated to destroy them in response to prior viral replication in the individual. Increases in sexual contact should contribute to this predicament by favouring evolution toward relatively high rates of replication early during infection. Because rapid replication and high mutation rate probably contribute to rapid progression of infections to aids, the interplay of sexual activity, replication rate, and mutation rate helps explain why HIV-1 has only recently caused a lethal pandemic, even though molecular data suggest that it may have been present in humans for more than a century. This interplay also offers an explanation for geographic differences in progression to cancer found among infections due to the other major group of human retroviruses, human T-cell lymphotropic viruses (HTLV). Finally, it suggests ways in which we can use natural selection as a tool to control the aids pandemic and prevent similar pandemics from arising in the future.


Human Immunodeficiency Virus Human Immunodeficiency Virus Type Mutation Rate Human Immunodeficiency Virus Infection High Mutation Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albert, J., Abrahamsson, B., Nagy, K., Aurelius, E., Gaines, H., Nyström, G. et al. 1990 Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AIDS 4, 107–112.PubMedCrossRefGoogle Scholar
  2. Anderson, M.G. & Clements, J.E. 1992 Two strains of SIV (mac) show differential transactivation mediated by sequences in the promoter. Virology 191, 559–568.PubMedCrossRefGoogle Scholar
  3. Bagasra, O., Hauptman, S.P., Lischner, H.W., Sachs, M. & Pomerantz, R.J. 1992 Detection of human immunodeficiency virus type 1 provirus in mononuclear cells by in situ polymerase chain reaction. N. Engl. J. Med. 326, 1385–1391.PubMedCrossRefGoogle Scholar
  4. Bakhanashvili, M. & Hizi, A. 1992 Fidelity of the reverse transcriptase of human immunodeficiency virus type 2. FEBS Lett. 306, 151–156.PubMedCrossRefGoogle Scholar
  5. Bakhanashvili, M. & Hizi, A. 1992a Fidelity of the RNA-dependent DNA synthesis exhibited by the reverse transcriptases of human immunodeficiency virus type 1 and type 2 and of murine leukemia virus: mispair extension frequencies. Biochemistry 31, 9393–9398.Google Scholar
  6. Bakhanashvili, M. & Hizi, A. 1993b The fidelity of the reverse transcriptases of human immunodeficiency viruses and murine leukemia virus, exhibited by the mispair extension frequencies, is sequence dependent and enzyme related. FEBS Lett. 319, 201–205.CrossRefGoogle Scholar
  7. Bartholomew, C., Saxinger, W.C., Clark, J.W., Gail, M., Dudgeon, A., Mahabir, B. et al. 1987 Transmission of HTLV I and HIV among homosexual men in Trinidad. J. Am. med. Ass. 257, 2604–2626.CrossRefGoogle Scholar
  8. Bell, G. 1993 Pathogen evolution within host individuals as a primary cause of sensescence. Genetica 91, 21–34.PubMedCrossRefGoogle Scholar
  9. Berneman, Z.N., Gartenhaus, R.B., Reitz, M.S., Blattner, W.A., Manns, A., Hanchard, B. et al. 1992 Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/ lymphoma and healthy carriers. Proc. natn. Acad. Sci. U.S.A. 89, 3005–3009.CrossRefGoogle Scholar
  10. Blattner, W.A. 1990 Epidemiology of HTLV-I and associated diseases. In Human retrovirology: HTLV (ed. W. A. Blattner), pp. 251–265. New York: Raven Press.Google Scholar
  11. Cheng-Mayer, C, Seto, D., Tateno, M. & Levy, J.A. 1988 Biologic features of HIV- 1 that correlate with virulence in the host. Science 240, 80–82.PubMedCrossRefGoogle Scholar
  12. Clark, J., Saxinger, C, Gibbs, W.N., Lofters, W., Lagranade, L., Deceulaer, K. et al. 1985 Seroepidemio-logic studies of human T-cell leukemia/lymphoma virus type I in Jamaica. Int. J. Cancer 36, 37–41.PubMedCrossRefGoogle Scholar
  13. Coffin, J.M. 1990 Genetic variation in retroviruses. In Applied virology research, volume 2. Virus variability, epidemiology and control (ed. E. Kurstak, R. G. Marusyk, F. A. Murphy & M.J. V. van Regenmortel), pp. 11–31. New York: Plenum.Google Scholar
  14. Connor, R.I., Mohri, H., Cao, Y.Z. & Ho, D.D. 1993 Increased viral burden and cytopathicity correlate temporally with CD4+ T lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals. J. Virol. 67, 1772–1777.PubMedGoogle Scholar
  15. De Leys, R., Vanderborght, B., Haeseveldt, M.V., Heyndrickx, L., van Geel, A., Wauters, C. et al. 1990 Isolation and partial characterization of an unusual human immunodeficiency retrovirus from two persons of westcentral African origin. J. Virol. 64, 1207–1216.PubMedGoogle Scholar
  16. Eigen, M. & Biebricher, C.K. 1988 Sequence space and quasispecies distribution. In RNA genetics, vol. 3 (ed. E. Domingo, J. J. Holland & P. Ahlquist), pp. 211-245. Boca Raton, Florida: CRC.Google Scholar
  17. Eigen, M. & Nieselt-Struwe, K. 1990 How old is the immunodeficiency virus? AIDS 4 (Suppl. 1), S85–93.PubMedCrossRefGoogle Scholar
  18. Embretson, J., Zupancic, M., Ribas, J.L., Burke, A., Racz, P., Tenner-Racz, K. et al. 1993 Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature 362, 359–362.PubMedCrossRefGoogle Scholar
  19. Ewald, P.W. 1991 Transmission modes and the evolution of virulence, with special reference to cholera, influenza and AIDS. Hum. Nature 2, 1–30.CrossRefGoogle Scholar
  20. Ewald, P.W. 1994 Evolution of infectious disease. New York: Oxford University Press.Google Scholar
  21. Fan, N., Gavalchin, J., Paul, B., Wells, K.H., Lane, M.J. & Poiesz, B.J. 1992 Infection of peripheral blood mononuclear cells and cell lines by cell-free human T-cell lymphoma/leukemia virus type I. J. clin. Microbiol. 30, 905–910.PubMedGoogle Scholar
  22. Fauci, A.S., Schnittman, S.M., Poli, G., Koenig, S. & Pantaleo, G. 1991 Immunopathogenic mechanisms in human immunodeficiency virus (HIV) infection. Ann. intern. Med. 114, 678–693.PubMedGoogle Scholar
  23. Gessain, A., Yanagihara, R., Franchini, G., Garruto, R.M., Jenkins, C.L., Ajdukiewicz, A.B. et al. 1991 Highly divergent molecular variants of human T-lymphotropic virus type I from isolated populations in Papua New Guinea and the Solomon Islands. Proc. natn. Acad. Sci. U.S.A. 88, 7694–7698.CrossRefGoogle Scholar
  24. Goodman, M.F., Creighton, S., Bloom, L.B. & Petruska, J. 1993 Biochemical basis of DNA replication fidelity. C.r. Biochem. Mol. Biol. 28, 83–126.CrossRefGoogle Scholar
  25. Goubau, P., Desmyter, J., Ghesquiere, J. & Kasereka, B. 1992 HTLV-II among pygmies. Nature 359, 201.PubMedCrossRefGoogle Scholar
  26. Gruters, R.A., Terpstra, F.G., Degoede, R.E.Y., Mulder, J.W., DeWolf, F., Schellekens, P.T.A. et al. 1991 Immunological and virological markers in individuals progressing from seroconversion to AIDS. AIDS 5, 837–844.PubMedCrossRefGoogle Scholar
  27. Gürtler, L.G., Hauser, P.H., Eberle, J., Von Brunn, A., Knapp, S., Zekeng, L. et al. 1994 A new subtype of human immunodeficiency virus type 1 (MVP-5180) from Cameroon. J. Virol. 68, 1581–1585.PubMedGoogle Scholar
  28. Halsey, N.A., Coberly, J.S., Holt, E., Coreil, J., Kissinger, P., Moulton, L.H. et al. 1992 Sexual behavior, smoking, and HIV-1 infection in Haitian women. J. Am. med. Ass. 267, 2062–2066.CrossRefGoogle Scholar
  29. Hamilton, W.D. 1980 Sex versus non-sex versus parasite. Oikos 35, 282–290.CrossRefGoogle Scholar
  30. Hino, S., Doi, H., Yoshikuni, H., Sugiyama, H., Ishimaru, T., Yamabe, T. et al. 1987 HTLV-I carrier mothers with high-titer antibody are at high risk as a source of infection. Jap. J. Cancer Res. 78, 1156–1158.Google Scholar
  31. Hino, S., Yamaguchi, K., Katamine, S., Amagasaki, T., Kinoshita, K., Yoshida, Y. et al. 1985 Mother-to-child transmission of human T-cell leukemia virus type-I. Jap. J. Cancer Res. 76, 474–480.Google Scholar
  32. Hizi, A., Tal, R., Shaharabany, M. & Loya, S. 1991 Catalytic properties of the reverse transcriptases of human immunodeficiency viruses type 1 and type 2. J. biol. Chem. 266, 6230–6239.PubMedGoogle Scholar
  33. Ho, G.Y.F., Nomura, A.M.Y., Nelson, K., Lee, H., Polk, B.F. & Blattner, W.A. 1991 Declining seroprevalence and transmission of HTLV-I in Japanese families who immigrated to Hawaii. Am. J. Epidemiol. 134, 981–987.PubMedGoogle Scholar
  34. Holland, J. 1993 Replication error, quaispecies populations, and extreme evolution rates of RNA viruses. In Emerging viruses (ed. S. Morse), pp. 203–218. New York: Oxford.Google Scholar
  35. Howell, R.M., Fitzgibbon, J.E., Noe, M., Ren, Z., Gocke, DJ., Schwartzer, T.A. et al. 1991 In vivo sequence variation of the human immunodeficiency virus type 1 env gene: Evidence for recombination among variants found in a single individual. AIDS Res. Hum. Retroviruses 7, 869–876.PubMedCrossRefGoogle Scholar
  36. Hübner, A., Kruhoffer, M., Grosse, F. & Krauss, G. 1992 Fidelity of human immunodeficiency virus type I reverse transcriptase in copying natural RNA. J. molec. Biol. 223, 595–600.PubMedCrossRefGoogle Scholar
  37. Ji, J.P. & Loeb, L.A. 1992 Fidelity of HIV-1 reverse transcriptase copying RNA in vitro. Biochemistry 31, 954–958.Google Scholar
  38. Kajiyama, W., Kashiwagi, S., Hayashi, J., Nomura, H., Ikematsu, H. & Okochi, K. 1986 Intrafamilial clustering of anti-ATLA persons. Am. J. Epidemiol. 124, 800–806.PubMedGoogle Scholar
  39. Kawase, K., Katamine, S., Moriuchi, R., Miyamoto, T., Kubota, K., Igarashi, H. et al. 1992 Maternal transmission of HTLV-1 other than through breast milk: discrepancy between the polymerase chain reaction positivity of cord blood samples for HTLV-1 and the subsequent seropositivity of individuals. Jap. J. Cancer Res. 83, 968–977.Google Scholar
  40. Kondo, T., Kono, H., Miyamoto, N., Yoshida, R., Toki, H., Matsumoto, I. et al. 1989 Age- and sex-specific cumulative rate and risk of ATLL for HTLV-I carriers. Int. J. Cancer 43, 1061–1064.PubMedCrossRefGoogle Scholar
  41. Kusuhara, K., Sonoda, S., Takahashi, K., Tokugawa, K., Fukushige, J. & Ueda, K. 1987 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 40, 755–757.PubMedCrossRefGoogle Scholar
  42. Levine, P.H., Manns, A., Jaffe, E.S., Colclough, G., Cavallaro, A., Reddy, G. et al. 1994 The effect of ethnic differences on the pattern of HTLV-I-associated T-cell leukemia/lymphoma (HATL) in the United States. Int. J. Cancer 56, 177–181.PubMedCrossRefGoogle Scholar
  43. Maloney, E.M., Biggar, R.J., Neel, J.V., Taylor, M.E., Hahn, B.H., Shaw, G.M. et al. 1992 Endemic human T-cell lymphotropic virus type II infection among isolated Brazilian Amerindians. J. infect. Dis. 166, 100–107.PubMedCrossRefGoogle Scholar
  44. McGuire, K.L., Curtiss, V.E., Larson, E.L. & Haseltine, W.A. 1993 Influence of human T-cell leukemia virus type I tax and rex on interleukin-2 gene expression. J. Virol. 67, 1590–1599.PubMedGoogle Scholar
  45. Monk, R.J., Malik, F.G., Stokesberry, D. & Evans, L.H. 1992 Direct determination of the point mutation rate of a murine retrovirus. J. Virol. 66, 3683–3689.PubMedGoogle Scholar
  46. Murphy, E.L. & Blattner, W. 1988 HTLV-I associated leukemia: A model for chronic retroviral diseases. Ann. Neurol. 23 (Suppl.), S174–180.PubMedCrossRefGoogle Scholar
  47. Murphy, E.L., Figueroa, J.P., Gibbs, W.N., Brathwaite, A., Holding-Cobham, M., Waters, D. et al. 1989 Sexual transmission of human T-lymphotropic virus type I (HTLV I). Ann. intern. Med. 111, 555–560.PubMedGoogle Scholar
  48. Murphy, E.L., Figueroa, J.P., Gibbs, W.N., Holding-Cobham, M., Cranston, B., Malley, K. et al. 1991 Human T-lymphotropic virus type-I (HTLV-I) seroprevalence in Jamaica. 1. Demographic determinants. Am. J. Epidemiol. 133, 1114–1124.PubMedGoogle Scholar
  49. Nagamine, M., Nakashima, Y., Uemura, S., Takei, H., Toda, T., Maehama, T. et al. 1991 DNA amplification of human T Lymphotropic virus type I (HTLV-I) proviral DNA in breast milk of HTLV-I carriers. J. infect. Dis. 164, 1024–1025.PubMedCrossRefGoogle Scholar
  50. Nkengasong, J.N., Peeters, M., van den Haesevelde, M., Musi, S.S., Willems, B., Ndumbe, P.M. et al. 1993 Antigenic evidence of the presence of the aberrant HIV-1 ANT70 virus in Cameroon and Gabon. AIDS 7, 1536–1538.PubMedCrossRefGoogle Scholar
  51. Nowak, M.A., May, R.M. & Anderson, R.M. 1990 The evolutionary dynamics of HIV-1 quasispecies and the development of immunodeficiency disease. AIDS 4, 1095–1103.PubMedCrossRefGoogle Scholar
  52. Padian, N., Marquis, L., Francis, D.P., Anderson, R.E., Rutherford, G.W., O’Malley, P.M. et al. 1987 Male-to-female transmission of human immunodeficiency virus. J. Am. med. Ass. 258, 788–790.CrossRefGoogle Scholar
  53. Piatak, M., Saag, M.S., Yang, L.C., Clark, S.J., Kappes, J.C., Luk, K.C. et al. 1993 High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science 259, 1749–1754.PubMedCrossRefGoogle Scholar
  54. Preston, B.D., Poiesz, B.J. & Loeb, L.A. 1988 Fidelity of HIV-I reverse transcriptase. Science 242, 1168.PubMedCrossRefGoogle Scholar
  55. Ratner, L., Philpott, T. & Trowbridge, D.B. 1991 Nucleotide sequence analysis of isolates of human T-lymphotropic virus type-1 of diverse geographical origins. AIDS Res. Hum. Retroviruses 7, 923–941.PubMedCrossRefGoogle Scholar
  56. Riedel, D.A., Evans, A.S., Saxinger, C. & Blattner, W. 1989 A historical study of human T lymphotropic virus type I transmission in Barbados. J. infect. Dis. 159, 603–609.PubMedCrossRefGoogle Scholar
  57. Roberts, J.D., Bebenek, K. & Kunkel, T.A. 1988 The accuracy of reverse transcriptase from HIV-1. Science 242, 1171–1173.PubMedCrossRefGoogle Scholar
  58. Rodriguez, E.M., de Moya, E.A., Guerrero, E., Monterroso, E.R., Quinn, T.C., Puello, E. et al. 1993 HIV-1 and HTLV-I in sexually transmitted disease clinics in the Dominican Republic. J. Acquired Immune Defic. Syndr. 6, 313–318.Google Scholar
  59. Sawada, T., Tohmatsu, J. & Obara, T. 1989 High risk of mother-to-child transmission of HTLV-I in p40tax antibody-positive mothers. Jap. J. Cancer Res. 80, 506–8.Google Scholar
  60. Scarlatti, G., Lombardi, V., Plebani, A., Principi, N., Vegni, C, Ferraris, G. et al. 1991 Polymerase chain reaction, virus isolation and antigen assay in HIV-1-antibody-positive mothers and their children. AIDS 5, 1173–1178.PubMedCrossRefGoogle Scholar
  61. Schellekens, P.T.A., Tersmette, M., Roos, M.T.L., Keet, R.P., Dewolf, F., Coutinho, R.A. et al. 1992 Biphasic rate of CD4+ cell count decline during progression to aids correlates with hiv-1 phenotype. AIDS 6, 665–669.PubMedCrossRefGoogle Scholar
  62. Schneweis K.E., Kleim J.-P., Bailly E., Niese D., Wagner N. & Brackmann H. H. 1990 Graded cytopathogenicity of the human immunodeficiency virus (HIV) in the course of HIV infection. Med. microbiol. Immunol. 179, 193–203.PubMedCrossRefGoogle Scholar
  63. Schwartz, J.B., Akin, J.S., Guilkey, D.K. & Pagueo, V. 1989 The effect of contraceptive prices on method choice in the Philippines, Jamaica and Thailand. In Choosing a contraceptive. Method choice in Asia and the United States (ed. R. A. Bulatao, J. A. Palmore & S. E. Ward), pp. 78–102. Boulder, Colorado: Westview Press.Google Scholar
  64. Shearer, G.M. & Clerici, M. 1991 Early T-helper cell defects in HIV infection. AIDS 5, 245–253.PubMedCrossRefGoogle Scholar
  65. Shimoyama, M. 1991 Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma: A report from the Lymphoma Study Group (1984–7). Br. med. Haematol. 79, 428–437.CrossRefGoogle Scholar
  66. Shioiri, S., Tachibana, N., Okayama, A., Ishihara, S., Tsuda, K., Essex, M. et al. 1993 Analysis of anti-tax antibody of HTLV-I carriers in an endemic area in Japan. Int. J. Cancer 53, 1–4.PubMedCrossRefGoogle Scholar
  67. Stuver, S.O., Tachibana, N., Okayama, A., Shioiri, S., Tsunetoshi, Y., Tsuda, K. et al. 1993 Heterosexual transmission of human T-cell leukemia/lymphoma virus type-I among married couples in southwestern Japan — an initial report from the Miyazaki cohort study. J. infect. Dis. 167, 57–65.PubMedCrossRefGoogle Scholar
  68. Suárez, P., Valcarcel, J. & Ortin, J. 1992 Heterogeneity of the mutation rates of influenza A viruses: Isolation of mutator mutants. J. Virol. 66, 2491–2494.PubMedGoogle Scholar
  69. Sugiyama, H., Doi, H., Yamaguchi, K., Tsuji, Y., Miyamoto, T. & Hino, S. 1986 Significance of postnatal mother-to-child transmission of human T-lymphotropic virus type-I on the development of adult T-cell leukemia/lymphoma. J. med. Virol. 20, 253–260.PubMedCrossRefGoogle Scholar
  70. Tajima, K. 1988 The T- and B-cell malignancy study group. The third nation-wide study on adult T-cell leukemia/lymphoma (ATL) in Japan: Characteristic patterns of HLA antigen and HTLV-I infection in ATL patients and their relatives. Int. J. Cancer 41, 505–512.CrossRefGoogle Scholar
  71. Tajima, K. 1990 The T- and B-cell malignancy study group. The fourth nation-wide study on adult T-cell leukemia/lymphoma (ATL) in Japan: estimates of risk of ATL and its geographical and clinical features. Int. J. Cancer 45, 237–243.PubMedCrossRefGoogle Scholar
  72. Tajima, K. & Ito, S. 1990 Prospective studies of HTLV-I and associated diseases in Japan. In Human retrovirology: HTLV (ed. W. A. Blattner), pp. 267–279. New York: Raven Press.Google Scholar
  73. Tajima, K., Tominaga, S., Suchi, T., Kawagoe, T., Komoda, H., Hinuma, Y. et al. 1982 Epidemiological analysis of the distribution of antibody to adult T-cell leukemia virus associated antigen (ATLA): Possible horizontal transmission of adult T-cell leukemia virus. Gann 73, 893–901.PubMedGoogle Scholar
  74. Take, H., Umemoto, M., Kusuhara, K. & Kuraya, K. 1993 Transmission routes of HTLV-I: an analysis of 66 families. Jap. J. Cancer Res. 84, 1265–1267.Google Scholar
  75. Takeuchi, Y., Nagumo, T. & Hoshino, H. 1988 Low fidelity of cell-free DNA synthesis by reverse transcriptase of human immunodeficiency virus. J. Virol. 62, 3900–3902.PubMedGoogle Scholar
  76. Temin, H.M. 1989a Retrovirus variation and evolution. Genome 31, 17–22.PubMedCrossRefGoogle Scholar
  77. Temin, H.M. 1989b Is HIV unique or merely different? J. Acquired Immune Defic. Syndr. 2, 1–9.Google Scholar
  78. Tersmette, M. & Miedema, F. 1990 Interactions between HIV and the host immune system in the pathogenesis of AIDS. AIDS 4 (Suppl. 1), S57–66.PubMedCrossRefGoogle Scholar
  79. Tremblay M., & Wainberg M. A. 1990 Neutralization of multiple HIV-1 isolates from a single subject by autologous sequential sera. J. infect. Dis. 162, 735–737.PubMedCrossRefGoogle Scholar
  80. Ueda, K., Kusuhara, K., Tokugawa, K., Miyazaki, C., Hoshida, C, Tokumura, K. et al. 1989 Cohort effect on HTLV-I seroprevalence in southern Japan. Lancet 2, 979.PubMedCrossRefGoogle Scholar
  81. Ueda, K., Kusuhara, K., Tokugawa, K., Miyazaki, C., Okada, K., Maeda, Y. et al. 1993 Mother-to-child transmission of human T-lymphotropic virus type I (HTLV-I): an extended follow-up study on children between 18 and 22–24 years old in Okinawa, Japan. Int. J. Cancer 53, 597–600.PubMedCrossRefGoogle Scholar
  82. Umemoto, M., Take, H., Kusuhara, K. & Kuraya, K. 1994 Risk of HTLV-I infection in Japanese women who are last in birth order. Cancer Lett. 76, 191–195.PubMedCrossRefGoogle Scholar
  83. Varela-Echavarria, A., Garvey, N., Preston, B.D. & Dougherty, J.P. 1992 Comparison of moloney murine leukemia virus mutation rate with the fidelity of its reverse transcriptase in vitro. J. biol. Chem. 267, 24681–24688.PubMedGoogle Scholar
  84. Wattel, E., Mariotti, M., Agis, F., Gordien, E., Le Coeur, F.F., Prin, L. et al. 1992 Quantification of HTLV-1 proviral copy number in peripheral blood of symptomless carriers from the French West Indies. J. Acquired Immune Defic. Syndr. 5, 943–946.Google Scholar
  85. Yamaguchi, K., Nishimura, H. & Takatsuki, K. 1983 Clinical features of malignant lymphoma and adult T-cell leukemia in Kumamoto. Rinsho Ketsekui 24, 1271–1276.Google Scholar
  86. Yoshida, M. 1994 Mechanism of transcriptional activation of viral and cellular genes by oncogenic protein of HTLV-I. Leukemia (suppl.) 8, s51–53.PubMedGoogle Scholar
  87. Yu, F., Itoyama, Y., Fujihara, K. & Goto, I. 1991 Natural killer (NK) cells in HTLV-I-associated myelopathy/tropical spastic paraparesis — decrease in NK cell subset populations and activity in HTLV-I seropositive individuals. J. Neuroimmunol. 33, 121–128.PubMedCrossRefGoogle Scholar

Copyright information

© The Royal Society 1997

Authors and Affiliations

  • Paul W. Ewald
    • 1
  1. 1.Department of BiologyAmherst CollegeAmherstUSA

Personalised recommendations