Chaplin J W
Santa Cruz AIDS Research Foundation, CA 95061, USA.
Med Hypotheses. 1999 Feb;52(2):133-46. doi: 10.1054/mehy.1997.0702.
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.
目前关于人类免疫缺陷病毒（HIV）在获得性免疫缺陷综合征（AIDS）发病机制中作用的模型并不完善，且与文献不一致。本文回顾了广泛的艾滋病研究，并提出了首个与文献完全一致的HIV发病机制模型。该模型基于T4细胞上CD4的抗体 - gp120复合物交联。该模型所涵盖的此前无法解释的观察结果包括免疫系统的早期定性缺陷、细胞因子表达的变化、“旁观者”T4细胞死亡，以及AIDS中T4细胞低感染率与T4细胞几乎完全消除之间的明显差异。详细介绍了基于该模型的一类新型药物。这些药物应能阻断导致AIDS的途径，并使HIV感染长期保持无症状。这些药物设计为易于修饰，因此该治疗方法对HIV臭名昭著的基于突变的耐药性具有免疫作用。
