Nowak M A, May R M, Anderson R M
Department of Zoology, University of Oxford, UK.
AIDS. 1990 Nov;4(11):1095-103. doi: 10.1097/00002030-199011000-00007.
This paper presents a theory to explain the development of immunodeficiency disease after a long and variable incubation period of infection with HIV-1. Two assumptions are central to the theory: (1) mutation via reverse transcription during viral replication can generate viral strains resistant to neutralization by antibodies specific to earlier mutants in a particular host; (2) the virus can kill the CD4-positive lymphocytes that play a role in mounting an immunological attack directed at the virus. The theory is examined via the development of a mathematical model which reveals that an increasing number of antigenically distinct viral strains may overwhelm the immune system of the host. As the viral diversity increases beyond a certain level the immune system is unable to suppress the population growth of all the strains simultaneously. The intuitive explanation of this pattern of model behaviour lies in the assumption that each virus can kill CD4-positive lymphocytes that are specific to any of the viral strains, but each lymphocyte only directs immunological attack against a single viral strain.(ABSTRACT TRUNCATED AT 250 WORDS)
本文提出了一种理论，用以解释在感染人类免疫缺陷病毒1型（HIV-1）后经过漫长且可变的潜伏期才出现免疫缺陷疾病的原因。该理论有两个核心假设：（1）病毒复制过程中通过逆转录产生的突变可生成对特定宿主中早期突变体的特异性抗体中和具有抗性的病毒株；（2）该病毒可杀死在针对该病毒发起免疫攻击中起作用的CD4阳性淋巴细胞。通过建立一个数学模型来检验该理论，该模型表明抗原性不同的病毒株数量不断增加可能会使宿主的免疫系统不堪重负。随着病毒多样性增加到一定程度以上，免疫系统无法同时抑制所有病毒株的种群增长。对这种模型行为模式的直观解释基于这样的假设：每种病毒都能杀死针对任何一种病毒株具有特异性的CD4阳性淋巴细胞，但每个淋巴细胞仅针对单一病毒株发起免疫攻击。（摘要截选至250字）
