HIV pathogenesis: gp120-antibody complexes bind CD4 and kill T4 cells--immunotoxin therapy should prevent the progression of HIV to AIDS.
Current models of the role of human immunodeficiency virus (HIV) in the pathogenesis of acquired immune deficiency syndrome (AIDS) are inadequate and inconsistent with the literature. This article reviews a wide range of AIDS research and proposes the first model of HIV pathogenesis that is entirely consistent with the literature. This model is based on antibody-gp120 complex crosslinking of CD4 on the T4 cells. Previously unexplained observations embraced by this model include early qualitative defects in the immune system, changes in cytokine expression, 'bystander' T4 cell death, and the apparent discrepancy between the low rate of T4 cell infection and the near-complete elimination of T4 cells in AIDS. A new class of drugs based on this model is detailed. These drugs should disrupt the pathway leading to AIDS and leave an HIV infection indefinitely asymptomatic. These drugs are designed to be readily modified, so the treatment is immune to HIV's notorious mutation-based drug resistance.
Chaplin
J W
JW
Santa Cruz AIDS Research Foundation, CA 95061, USA. scarf@scarf.org
D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000936:Antigen-Antibody Complex / Q000378:metabolism; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017635:Clonal Anergy; D003602:Cytotoxicity, Immunologic; D006678:HIV / Q000276:immunology / Q000472:pathogenicity; D015483:HIV Antibodies / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000209:etiology / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008954:Models, Biological
D000936:Antigen-Antibody Complex; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D000922:Immunotoxins