Viral complementation allows HIV-1 replication without integration.
Viral complementation allows HIV-1 replication without integration.
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DOI：
10.1186/1742-4690-5-60
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发表时间：
2008-07-09
期刊：
影响因子：
3.3
通讯作者：
Levy, David N.
中科院分区：
文献类型：
--
作者：
Gelderblom, Huub C.;Vatakis, Dimitrios N.;Burke, Sean A.;Lawrie, Steven D.;Bristol, Gregory C.;Levy, David N.
HIV-1 DNA整合到细胞染色质中是高水平病毒基因表达和产生新病毒体所必需的。然而，大多数HIV-1 DNA仍然是未整合的，通常被认为是复制的死胡同。已经报道了来自未整合的DNA的有限量的早期基因表达，但是病毒复制在仅含有未整合的DNA的细胞中不进一步进行。细胞的多重感染是常见的，并且被整合的前病毒有效感染的细胞通常也含有未整合的HIV-1 DNA。在这里，我们研究了整合的前病毒对未整合的HIV-1 DNA（UDNA）的影响。我们采用报告病毒和定量真实的时间PCR检测整合和非整合HIV-1共感染过程中的基因表达和病毒复制。大多数细胞只含有uDNA显示没有检测到的荧光报告基因插入到早期（Rev独立）和晚期（Rev依赖）的位置在HIV-1基因组中的表达。与整合的前病毒共感染导致显示uDNA早期基因表达的细胞数量增加数倍，并有效地驱动uDNA进入晚期基因表达。我们发现，共同感染会产生病毒粒子，这些病毒粒子将uDNA衍生的基因组包装并递送到细胞中;这样，uDNA通过病毒互补完成其复制周期。在第二轮感染期间，uDNA衍生的基因组与整合的前病毒衍生的基因组进行重组。这种新的逆转录病毒复制模式允许病毒存活，否则这些病毒将由于整合失败而丢失，放大了细胞共感染的有效量，增加了复制的HIV-1基因库，并通过聚合和重组的错误增加了多样化的机会。
The integration of HIV-1 DNA into cellular chromatin is required for high levels of viral gene expression and for the production of new virions. However, the majority of HIV-1 DNA remains unintegrated and is generally considered a replicative dead-end. A limited amount of early gene expression from unintegrated DNA has been reported, but viral replication does not proceed further in cells which contain only unintegrated DNA. Multiple infection of cells is common, and cells that are productively infected with an integrated provirus frequently also contain unintegrated HIV-1 DNA. Here we examine the influence of an integrated provirus on unintegrated HIV-1 DNA (uDNA). We employed reporter viruses and quantitative real time PCR to examine gene expression and virus replication during coinfection with integrating and non-integrating HIV-1. Most cells which contained only uDNA displayed no detected expression from fluorescent reporter genes inserted into early (Rev-independent) and late (Rev-dependent) locations in the HIV-1 genome. Coinfection with an integrated provirus resulted in a several fold increase in the number of cells displaying uDNA early gene expression and efficiently drove uDNA into late gene expression. We found that coinfection generates virions which package and deliver uDNA-derived genomes into cells; in this way uDNA completes its replication cycle by viral complementation. uDNA-derived genomes undergo recombination with the integrated provirus-derived genomes during second round infection. This novel mode of retroviral replication allows survival of viruses which would otherwise be lost because of a failure to integrate, amplifies the effective amount of cellular coinfection, increases the replicating HIV-1 gene pool, and enhances the opportunity for diversification through errors of polymerization and recombination.
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影响因子：
56.9
作者：
BUKRINSKY, MI;STANWICK, TL;STEVENSON, M
通讯作者：
STEVENSON, M
DOI：
10.1073/pnas.94.24.13193
发表时间：
1997-11-25
影响因子：
11.1
作者：
Chun, TW;Stuyver, L;Fauci, AS
通讯作者：
Fauci, AS
影响因子：
56.9
作者：
COFFIN, JM
通讯作者：
COFFIN, JM
影响因子：
32.4
作者：
Brooks, DG;Hamer, DH;Zack, JA
通讯作者：
Zack, JA
影响因子：
5.5
作者：
Cara, Andrea;Klotman, Mary E.
通讯作者：
Klotman, Mary E.