Superinfection of defective human immunodeficiency virus type 1 with different subtypes of wild-type virus efficiently produces infectious variants with the initial viral phenotypes by complementation followed by recombination
Superinfection of defective human immunodeficiency virus type 1 with different subtypes of wild-type virus efficiently produces infectious variants with the initial viral phenotypes by complementation followed by recombination
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DOI：
10.1016/j.micinf.2008.01.012
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发表时间：
2008-04-01
影响因子：
5.8
通讯作者：
Ikuta, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Iwabu, Yukie;Mizuta, Hiroyuki;Ikuta, Kazuyoshi
人类免疫缺陷病毒1型（HIV-1）的重复感染率越来越高，导致HIV-1的变异越来越多，这一点可以通过循环重组形式（CRF）的出现得到证明。我们最近报道了一个持续复制缺陷亚型B感染的细胞克隆，L-2，与CRF15_01B的重叠感染的互补。L-2细胞由于在pol蛋白酶处的一个碱基插入而持续产生未成熟颗粒。超感染细胞中的前病毒携带两种亚型，并产生具有成熟形态的颗粒。在这项研究中，我们研究了可能的重组后互补产生复制能力的变体，通过使用三个细胞克隆制备的超感染L-2细胞。单个克隆主要表达初始亚型B衍生的成熟Gag蛋白。然而，病毒颗粒在pol处携带具有突变的亚型B和野生型CRF15_01 B，表明产生了具有杂合RNA的病毒体。有趣的是，随着后代的无细胞传代，缺陷颗粒消失，并被pol区域中的异源重组体取代，所述异源重组体具有来自表达亚型B表型的CRF 15_01 B的序列。因此，即使是一种有缺陷的持续性HIV-1也可以通过重叠感染介导的互补和随后的重组而变得有复制能力。这些发现表明，长寿命的感染细胞作为重复感染的受体的重要性。(C)2008年，Elsevier Masson SAS。All rights reserved.
Superinfection rates of human immunodeficiency virus type 1 (HIV-1) have increasingly been leading to more variation in HIV-1, as evidenced by the emergence of circulating recombinant forms (CRFs). We recently reported complementation in a persistently replication-defective subtype B-infected cell clone, L-2, by superinfection with CRF15_01B. The L-2 cells continuously produce immature particles due to a one-base insertion at pol protease. Proviruses in the superinfected cells carried both subtypes and produced particles with a mature morphology. In this study, we examined possible recombination following complementation to generate replication-competent variants by using three cell clones prepared from superinfected L-2 cells. The individual clones predominantly expressed the initial subtype B-derived mature Gag proteins. However, the viral particles carried both subtype B with the mutation and wild-type CRF15_01B at pol, suggesting the generation of virions with heterozygous RNAs. Interestingly, with cell-free passages of the progeny, defective particles disappeared, and were replaced with heterogeneous recombinants in the pol region with sequences derived from CRF15_01B that expressed subtype B phenotype. Thus, even a defective form of persistent HIV-1 can become replication-competent through superinfection-mediated complementation followed by recombination. These findings suggest the significance of long-lived infected cells as recipients for superinfection. (C) 2008 Elsevier Masson SAS. All rights reserved.