QUANTITATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION KINETICS

QUANTITATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION KINETICS
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DOI:
10.1128/jvi.67.4.2182-2190.1993
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发表时间:
1993-04-01
影响因子:
5.4
通讯作者:
MARTIN, MA
MARTIN, MA
中科院分区:
医学2区
文献类型:
--
作者:
DIMITROV, DS;WILLEY, RL;MARTIN, MA

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1型人免疫缺陷病毒(HIV-1)对CD4阳性人T细胞的组织培养感染分三个阶段进行:(i)感染开始后的一段时间,在此期间不产生可检测的病毒;(ii)可以测量到释放的子代病毒粒子的急剧增加,随后达到峰值的阶段;和(iii)病毒产生下降的最后阶段。在这项研究中,我们推导出方程描述的HIV-1积累在细胞培养上清液中的动力学在多轮感染。我们的分析表明,影响HIV-1感染动力学的关键参数是感染速率常数k = Inn/t(i),其中n是一个细胞产生的感染性病毒体的数量(约10(2)),t(i)是病毒感染一个完整周期所需的时间(通常为3至4天)。特别值得注意的是,我们发现HIV-1在细胞间传播过程中的感染性比无细胞病毒原液的感染性高10(2)至10(3)倍,无细胞病毒原液是通常用于启动组织培养感染的接种物。我们还证明了HIV-1 tat突变体的缓慢感染动力学不是由于较长的复制时间,而是反映了每个周期产生的感染性颗粒数量较少。
Tissue culture infections of CD4-positive human T cells by human immunodeficiency virus type 1 (HIV-1) proceed in three stages: (i) a period following the initiation of an infection during which no detectable virus is produced; (ii) a phase in which a sharp increase followed by a peak of released progeny virions can be measured; and (iii) a final period when virus production declines. In this study, we have derived equations describing the kinetics of HIV-1 accumulation in cell culture supernatants during multiple rounds of infection. Our analyses indicated that the critical parameter affecting the kinetics of HIV-1 infection is the infection rate constant k = Inn/t(i), where n is the number of infectious virions produced by one cell (about 10(2)) and t(i) is the time required for one complete cycle of virus infection (typically 3 to 4 days). Of particular note was our finding that the infectivity of HIV-1 during cell-to-cell transmission is 10(2) to 10(3) times greater than the infectivity of cell-free virus stocks, the inocula commonly used to initiate tissue culture infections. We also demonstrated that the slow infection kinetics of an HIV-1 tat mutant is not due to a longer replication time but reflects the small number of infectious particles produced per cycle.