Antigenic diversity thresholds and the development of AIDS.

Longitudinal studies of patients infected with HIV-1 reveal a long and variable incubation period between infection and the development of AIDS. Data from a small number of infected patients show temporal changes in the number of genetically distinct strains of the virus throughout the incubation period, with a slow but steady rise in diversity during the progression to disease. A mathematical model of the dynamic interaction between viral diversity and the human immune system suggests the existence of an antigen diversity threshold, below which the immune system is able to regulate viral population growth but above which the virus population induces the collapse of the CD4+ lymphocyte population. The model suggests that antigenic diversity is the cause, not a consequence, of immunodeficiency disease. The model is compared with available data, and is used to assess how the timing of the application of chemotherapy or immunotherapy influences the rate of progress to disease.

[1]  R. Redfield,et al.  Type-restricted neutralization of molecular clones of human immunodeficiency virus. , 1988, Science.

[2]  Andreas Meyerhans,et al.  Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations , 1989, Cell.

[3]  Christine A. Lee,et al.  Serial CD4 lymphocyte counts and development of AIDS , 1991, The Lancet.

[4]  A. Ades,et al.  Children born to women with HIV-1 infection: natural history and risk of transmission , 1991, The Lancet.

[5]  P. Simmonds,et al.  Concurrent evolution of human immunodeficiency virus type 1 in patients infected from the same source , 2022 .

[6]  David Looney,et al.  Biologically diverse molecular variants within a single HIV-1 isolate , 1988, Nature.

[7]  W. Rozenbaum,et al.  EFFECTS OF ZIDOVUDINE IN 365 CONSECUTIVE PATIENTS WITH AIDS OR AIDS-RELATED COMPLEX , 1988, The Lancet.

[8]  J. Shih,et al.  Association of the virus-like infectious agent originally reported in patients with AIDS with acute fatal disease in previously healthy non-AIDS patients. , 1989, The American journal of tropical medicine and hygiene.

[9]  J. Levy,et al.  Changing concepts in HIV infection: challenges for the 1990s. , 1990, AIDS.

[10]  D. Stuart,et al.  Structural and serological evidence for a novel mechanism of antigenic variation in foot-and-mouth disease virus , 1990, Nature.

[11]  S D Kemp,et al.  Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). , 1989, Science.

[12]  M. Nowak.  HIV mutation rate , 1990, Nature.

[13]  J. Goudsmit,et al.  Evolution of sequences encoding the principal neutralization epitope of human immunodeficiency virus 1 is host dependent, rapid, and continuous. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[14]  G. Georgsson,et al.  Antigenic drift in visna: virus variation during long-term infection of Icelandic sheep. , 1983, The Journal of general virology.

[15]  J. Wasserman,et al.  Immunological changes in primary HIV‐1 infection , 1990, AIDS.

[16]  C. Cheng‐Mayer,et al.  Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp!20 gene , 1991, Nature.

[17]  J. Maclouf.  Cell-Cell Signalling , 1985 .

[18]  K Bebenek,et al.  The accuracy of reverse transcriptase from HIV-1. , 1988, Science.

[19]  H. Temin,et al.  Determination of the rate of base-pair substitution and insertion mutations in retrovirus replication , 1988, Journal of virology.

[20]  D. Ho,et al.  Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. , 1989, The New England journal of medicine.

[21]  M. Nowak,et al.  Error thresholds of replication in finite populations mutation frequencies and the onset of Muller's ratchet. , 1989, Journal of theoretical biology.

[22]  L. Loeb,et al.  Fidelity of HIV-1 reverse transcriptase. , 1988, Science.

[23]  K. Vickerman.  Antigenic variation in trypanosomes , 1978, Nature.

[24]  G. Shaw,et al.  Extensive variation of human immunodeficiency virus type-1 in vivo , 1988, Nature.

[25]  C. Cheng‐Mayer,et al.  Viral determinants of human immunodeficiency virus type 1 T-cell or macrophage tropism, cytopathogenicity, and CD4 antigen modulation , 1990, Journal of virology.

[26]  J. Albert,et al.  Distinct replicative and cytopathic characteristics of human immunodeficiency virus isolates , 1988, Journal of virology.