HIGH TITERS OF CYTOPATHIC VIRUS IN PLASMA OF PATIENTS WITH SYMPTOMATIC PRIMARY HIV-1 INFECTION
HIGH TITERS OF CYTOPATHIC VIRUS IN PLASMA OF PATIENTS WITH SYMPTOMATIC PRIMARY HIV-1 INFECTION
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DOI：
10.1056/nejm199104043241404
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发表时间：
1991-04-04
影响因子：
158.5
通讯作者：
SHAW, GM
中科院分区：
文献类型：
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作者：
CLARK, SJ;SAAG, MS;SHAW, GM
背景人类免疫缺陷病毒（HIV-1）的原发性感染经常引起急性自限性病毒综合征。为了研究病毒复制，宿主的免疫反应和临床疾病之间的关系，在感染的初始阶段，我们进行了定量，分子和生物学分析的传染性HIV-1的血液和血浆中的3例有症状的原发性感染和其中之一的性伴侣。在原发感染的8周期间，HIV-1频繁地在血浆和外周血单个核细胞（PBMC）的稀释液中培养，并且HIV-1抗原和抗体的水平通过酶联免疫吸附试验和免疫印迹法依次测定。复制能力的HIV-1前病毒的克隆和生物学特性。在症状发作后6至15天，在所有3名患者的血浆中检测到高滴度的感染性HIV-1（每毫升血浆10至10（3）个组织培养感染剂量）和病毒p24抗原。这些滴度在第27天急剧下降，并且下降与抗病毒抗体水平的增加和症状的消退相一致。从血浆和PBMC中获得的病毒的连续分离物，以及来自两个分子前病毒克隆的病毒，对正常供体PBMC和永生化T细胞具有高度致细胞病变性，尽管血浆中病毒滴度显著降低。原发性、有症状的HIV-1感染与高滴度的致细胞病变的、有复制能力的病毒株相关，并且在这种感染期间，潜在的感染性增强。有效控制HIV-1在原发感染期间的复制意味着激活临床上重要的免疫防御机制，这值得进一步研究与抗病毒治疗和疫苗的开发有关。
Background. Primary infection with the human immunodeficiency virus (HIV-1) frequently causes an acute, self-limited viral syndrome. To examine the relations among viral replication, the immune response of the host, and clinical illness during this initial phase of infection, we undertook a quantitative, molecular, and biologic analysis of infectious HIV-1 in the blood and plasma of three patients with symptomatic primary infection and of a sexual partner of one of them.Methods. During an eight-week period of primary infection, HIV-1 was cultured frequently in dilutions of plasma and peripheral-blood mononuclear cells (PBMC), and levels of HIV-1 antigen and antibody were determined sequentially by enzyme-linked immunosorbent assay and immunoblotting. Replication-competent HIV-1 proviruses were cloned and characterized biologically.Results. Six to 15 days after the onset of symptoms, high titers of infectious HIV-1 (from 10 to 10(3) tissue-culture-infective doses per milliliter of plasma) and viral p24 antigen were detected in the plasma of all three patients. These titers fell precipitously by day 27, and the decline coincided with an increase in the levels of antiviral antibodies and the resolution of symptoms. Sequential isolates of virus from plasma and PBMC obtained throughout the period of primary infection, as well as virus derived from two molecular proviral clones, were highly cytopathic for normal-donor PBMC and immortalized T cells, despite the marked reduction in the titers of virus in plasma.Conclusions. Primary, symptomatic HIV-1 infection is associated with high titers of cytopathic, replication-competent viral strains, and during such infection potential infectivity is enhanced. Effective control of HIV-1 replication during primary infection implies the activation of clinically important mechanisms of immune defense that merit further examination in relation to the development of antiviral therapy and vaccines.