REPLICATION OF PATIENT ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN T-CELLS - A SPECTRUM OF RATES AND EFFICIENCIES OF ENTRY
REPLICATION OF PATIENT ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN T-CELLS - A SPECTRUM OF RATES AND EFFICIENCIES OF ENTRY
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DOI：
10.1073/pnas.89.6.2223
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发表时间：
1992-03-15
影响因子：
11.1
通讯作者：
ROBINSON, HL
中科院分区：
文献类型：
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作者：
FERNANDEZLARSSON, R;SRIVASTAVA, KK;ROBINSON, HL
人类免疫缺陷病毒1型（HIV-1）的分离株经历许多不同的复制速率，复制的时间过程由宿主细胞和病毒决定。最近，我们证明了四种CD 4 + T细胞系对实验室毒株NL 4 -3的容许性与病毒进入的速率和效率相关。在这项研究中，我们分析了复制的“慢/低”分离株从艾滋病前感染期和两个“快/高”分离株从艾滋病感染期，以确定在病毒的生命周期中的哪些步骤确定患者分离株的生长特征的差异。患者分离株的生长差异与病毒生命周期的入组差异相关，但与入组后步骤无关。两种快速/高水平患者分离株（SF 33和SF 216）在C8166细胞中小于或等于0.5小时内、在促分裂原刺激的外周血单核细胞中小于或等于1小时内以及在H9细胞中小于或等于2.5小时内进入50%。相比之下，3类慢/低患者分离株50%进入C8166细胞需要1小时，50%进入外周血单核细胞需要3小时，50%进入H9细胞需要5-6小时。进入效率与进入速率相关，与H9细胞相比，快速/高病毒在C8166上的滴度高2倍，而慢速/低病毒在C8166上的滴度高5倍。实验室菌株NL 4 -3显示出中等的进入速率和效率。这些数据表明，入口特征是患者分离株致病潜力的主要决定因素。
Isolates of human immunodeficiency virus type 1 (HIV-1) undergo many different rates of replication, with the time course of replication being determined by the host cell and the virus. Recently, we demonstrated that the permissiveness of four CD4+ T-cell lines for the laboratory strain NL4-3 correlated with the rate and efficiency of virus entry. In this study, we have analyzed the replication of a "slow/low" isolate from the pre-AIDS period of infection and two "rapid/high" isolates from the AIDS period of infection to determine which steps in the virus life cycle determine differences in the growth characteristics of patient isolates. Differences in the growth of the patient isolates correlated with differences in entry but not postentry steps of the virus life cycle. The two rapid/high patient isolates (SF33 and SF216) underwent 50% entry in less-than-or-equal-to 0.5 hr in C8166 cells, in less-than-or-equal-to 1 hr in mitogen-stimulated peripheral blood mononuclear cells, and in greater-than-or-equal-to 2.5 hr in H9 cells. In contrast, a class 3 slow/low patient isolate required 1 hr for 50% entry into C8166 cells, 3 hr for 50% entry into peripheral blood mononuclear cells, and 5-6 hr for 50% entry into H9 cells. Entry efficiency correlated with entry rate, with the rapid/high viruses having a 2-fold higher titer and the slow/low virus having a 5-fold higher titer on C8166 than H9 cells. The laboratory strain NL4-3 displayed intermediate rates and efficiencies of entry. These data demonstrate that entry characteristics are major determinants of the pathogenic potential of patient isolates.