VIROLOGICAL AND IMMUNOLOGICAL CHARACTERIZATION OF LONG-TERM SURVIVORS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION
VIROLOGICAL AND IMMUNOLOGICAL CHARACTERIZATION OF LONG-TERM SURVIVORS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION
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DOI：
10.1056/nejm199501263320401
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发表时间：
1995-01-26
影响因子：
158.5
通讯作者：
HO, DD
中科院分区：
文献类型：
--
作者：
CAO, YZ;QIN, LM;HO, DD
背景。在大多数感染1型人类免疫缺陷病毒（HIV - 1）的个体中，在血清转化后的10年内会出现免疫缺陷的临床或实验室证据，但有少数感染者在十多年里保持健康且免疫功能正常。对这些被称为长期存活者的个体进行研究，可能会为针对获得性免疫缺陷综合征的预防和治疗干预措施的研发提供重要线索。
方法与结果。我们研究了10名血清阳性个体，尽管感染HIV - 1已达12至15年，但他们仍无症状，且CD4⁺淋巴细胞计数正常且稳定。血浆培养均未检测到有传染性的病毒。然而，通过一种灵敏的分支DNA信号放大检测法，在4名个体中检测到了与颗粒相关的HIV - 1 RNA，而在另外5名个体中，HIV - 1 RNA水平过低无法检测到。通过标准的有限稀释培养法，在3名个体的外周血单个核细胞（PBMC）中检测到了有传染性的HIV - 1，并且使用去除CD8⁺细胞的培养法从另一名个体中恢复出了有传染性的病毒。其他6名个体的PBMC中未检测到有传染性的病毒。一种定量聚合酶链反应检测法显示，所有个体的PBMC中都可检测到病毒DNA，但滴度较低。总体而言，长期存活者血浆和PBMC中的病毒载量比进行性疾病患者通常的病毒载量低几个数量级。
没有体外证据表明宿主CD4⁺淋巴细胞对HIV - 1感染有抵抗力。然而，长期存活者具有强烈的抑制病毒的CD8⁺淋巴细胞反应和强大的中和抗体反应。在2名个体中，病毒复制的动力学与存在一种明显减毒的HIV - 1毒株相符。
结论。尽管感染了HIV - 1但多年无症状的个体体内HIV - 1水平较低，并且具有强烈的病毒特异性免疫反应以及病毒一定程度的减毒。
Background. In most subjects infected with human immunodeficiency virus type 1 (HIV-1), clinical or laboratory evidence of immunodeficiency develops within 10 years of seroconversion, but a few infected people remain healthy and immunologically normal for more than a decade. Studies of these subjects, termed long-term survivors, may yield important clues for the development of prophylactic and therapeutic interventions against the acquired immunodeficiency syndrome.Methods and Results. We studied 10 seropositive subjects who remained asymptomatic with normal and stable CD4+ lymphocyte counts despite 12 to 15 years of HIV-1 infection. Plasma cultures were uniformly negative for infectious virus. However, particle-associated HIV-1 RNA was detected in four subjects with a sensitive branched-DNA signal-amplification assay, whereas in five others the levels of HIV-1 RNA were too low to detect. Infectious HIV-1 was detected in peripheral-blood mononuclear cells (PBMC) of three subjects by standard limiting-dilution cultures, and infectious virus was recovered from another subject with use of a CD8-depleted culture. The other six subjects had no detectable infectious virus in their PBMC. A quantitative polymerase-chain-reaction assay revealed that all subjects had detectable but low titers of viral DNA in PBMC. Overall, the viral burden in the plasma and PBMC of long-term survivors was orders of magnitude lower than that typically found in subjects with progressive disease.There was no in vitro evidence of resistance by host CD4+ lymphocytes to HIV-1 infection. However, longterm survivors had a vigorous, virus-inhibitory CD8+ lymphocyte response and a strong neutralizing-antibody response. In two subjects the kinetics of viral replication was consistent with the presence of a substantially attenuated strain of HIV-1.Conclusions. Subjects who remain asymptomatic for many years despite HIV-1 infection have low levels of HIV-1 and a combination of strong virus-specific immune responses with some degree of attenuation of the virus.