Duesberg P H
Department of Molecular Biology, University of California, Berkeley 94720.
Proc Natl Acad Sci U S A. 1989 Feb;86(3):755-64. doi: 10.1073/pnas.86.3.755.
AIDS is an acquired immunodeficiency syndrome defined by a severe depletion of T cells and over 20 conventional degenerative and neoplastic diseases. In the U.S. and Europe, AIDS correlates to 95% with risk factors, such as about 8 years of promiscuous male homosexuality, intravenous drug use, or hemophilia. Since AIDS also correlates with antibody to a retrovirus, confirmed in about 40% of American cases, it has been hypothesized that this virus causes AIDS by killing T cells. Consequently, the virus was termed human immunodeficiency virus (HIV), and antibody to HIV became part of the definition of AIDS. The hypothesis that HIV causes AIDS is examined in terms of Koch's postulates and epidemiological, biochemical, genetic, and evolutionary conditions of viral pathology. HIV does not fulfill Koch's postulates: (i) free virus is not detectable in most cases of AIDS; (ii) virus can only be isolated by reactivating virus in vitro from a few latently infected lymphocytes among millions of uninfected ones; (iii) pure HIV does not cause AIDS upon experimental infection of chimpanzees or accidental infection of healthy humans. Further, HIV violates classical conditions of viral pathology. (i) Epidemiological surveys indicate that the annual incidence of AIDS among antibody-positive persons varies from nearly 0 to over 10%, depending critically on nonviral risk factors. (ii) HIV is expressed in less than or equal to 1 of every 10(4) T cells it supposedly kills in AIDS, whereas about 5% of all T cells are regenerated during the 2 days it takes the virus to infect a cell. (iii) If HIV were the cause of AIDS, it would be the first virus to cause a disease only after the onset of antiviral immunity, as detected by a positive "AIDS test." (iv) AIDS follows the onset of antiviral immunity only after long and unpredictable asymptomatic intervals averaging 8 years, although HIV replicates within 1 to 2 days and induces immunity within 1 to 2 months. (v) HIV supposedly causes AIDS by killing T cells, although retroviruses can only replicate in viable cells. In fact, infected T cells grown in culture continue to divide. (vi) HIV is isogenic with all other retroviruses and does not express a late, AIDS-specific gene. (vii) If HIV were to cause AIDS, it would have a paradoxical, country-specific pathology, causing over 90% Pneumocystis pneumonia and Kaposi sarcoma in the U.S. but over 90% slim disease, fever, and diarrhea in Africa.(viii) It is highly improbable that within the last few years two viruses (HIV-1 and HIV-2) that are only 40% sequence-related would have evolved that could both cause the newly defined syndrome AIDS. Also, viruses are improbable that kill their only natural host with efficiencies of 50-100%, as is claimed for HIVs. It is concluded that HIV is not sufficient for AIDS and that it may not even be necessary for AIDS because its activity is just as low in symptomatic carriers as in asymptomatic carriers. The correlation between antibody to HIV and AIDS does not prove causation, because otherwise indistinguishable diseases are now set apart only on the basis of this antibody. I propose that AIDS is not a contagious syndrome caused by one conventional virus or microbe. No such virus or microbe would require almost a decade to cause primary disease, nor could it cause the diverse collection of AIDS diseases. Neither would its host range be as selective as that of AIDS, nor could it survive if it were as inefficiently transmitted as AIDS. Since AIDS is defined by new combinations of conventional diseases, it may be caused by new combinations of conventional pathogens, including acute viral or microbial infections and chronic drug use and malnutrition. The long and unpredictable intervals between infection with HIV and AIDS would then reflect the thresholds for these pathogenic factors to cause AIDS diseases, instead of an unlikely mechanism of HIV pathogenesis.
艾滋病是一种获得性免疫缺陷综合征,其特征为T细胞严重耗竭以及20多种常见的退行性和肿瘤性疾病。在美国和欧洲,95%的艾滋病病例与危险因素相关,如约8年的混乱男同性恋行为、静脉注射吸毒或血友病。由于艾滋病也与一种逆转录病毒的抗体相关,在美国约40%的病例中得到证实,因此有人推测这种病毒通过杀死T细胞导致艾滋病。因此,该病毒被称为人类免疫缺陷病毒(HIV),HIV抗体成为艾滋病定义的一部分。根据科赫法则以及病毒病理学的流行病学、生化、遗传和进化条件,对HIV导致艾滋病这一假说进行了检验。HIV不符合科赫法则:(i)在大多数艾滋病病例中检测不到游离病毒;(ii)病毒只能通过在体外从数百万未感染的淋巴细胞中重新激活少数潜伏感染的淋巴细胞来分离;(iii)将纯HIV实验性感染黑猩猩或意外感染健康人不会导致艾滋病。此外,HIV违反了病毒病理学的经典条件。(i)流行病学调查表明,抗体阳性者中艾滋病的年发病率从近0到超过10%不等,这主要取决于非病毒危险因素。(ii)在艾滋病中,HIV在其据称杀死的每10⁴个T细胞中表达的比例小于或等于1个,而在病毒感染一个细胞所需的2天时间内,约5%的所有T细胞会再生。(iii)如果HIV是艾滋病的病因,它将是第一种仅在抗病毒免疫开始后(通过阳性的“艾滋病检测”检测到)才导致疾病的病毒。(iv)艾滋病仅在平均8年的漫长且不可预测的无症状期后才随着抗病毒免疫的开始而出现,尽管HIV在1至2天内复制并在1至2个月内诱导免疫。(v)HIV据称通过杀死T细胞导致艾滋病,尽管逆转录病毒只能在活细胞中复制。事实上,在培养中生长的受感染T细胞会继续分裂。(vi)HIV与所有其他逆转录病毒具有同基因性,并且不表达晚期的、艾滋病特异性基因。(vii)如果HIV导致艾滋病,它将具有自相矛盾的、因国家而异的病理学特征,在美国导致超过90%的肺孢子菌肺炎和卡波西肉瘤,但在非洲导致超过90%的消瘦病、发热和腹泻。(viii)在过去几年中,两种序列相关性仅为40%的病毒(HIV - 1和HIV - 2)都能导致新定义的艾滋病综合征,这种可能性极小。而且,像声称的HIV那样以50 - 100%的效率杀死其唯一天然宿主的病毒是不太可能存在的。结论是,HIV不足以导致艾滋病,甚至可能对艾滋病来说并非必要条件,因为其在有症状携带者中的活性与无症状携带者中的活性一样低。HIV抗体与艾滋病之间的相关性并不能证明因果关系,因为否则无法区分的疾病现在仅基于这种抗体而被区分开来。我提出艾滋病不是由一种传统病毒或微生物引起的传染性综合征。没有这样的病毒或微生物会需要近十年时间来引发原发性疾病,也不会导致艾滋病所包含的多种疾病。其宿主范围也不会像艾滋病那样具有选择性,而且如果它像艾滋病那样传播效率低下,也无法存活。由于艾滋病是由传统疾病的新组合定义的,它可能是由传统病原体的新组合引起的,包括急性病毒或微生物感染以及慢性药物使用和营养不良。那么,感染HIV与艾滋病之间漫长且不可预测的间隔将反映这些致病因素导致艾滋病相关疾病的阈值,而不是HIV发病机制的一种不太可能的情况。