Kinomoto Masanobu, Mukai Tetsu, Li Yong-Gang, Iwabu Yukie, Warachit Jiranan, Palacios J Alejandro, Ibrahim Madiha S, Tsuji Shoutaro, Goto Toshiyuki, Ikuta Kazuyoshi
Department of Virology, Research Institute for Microbial Disease, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Microbes Infect. 2004 Aug;6(10):911-8. doi: 10.1016/j.micinf.2004.05.003.
The infection and subsequent replication rates of human immunodeficiency virus type 1 (HIV-1) affect the pathogenicity. The initial stage of HIV-1 infection is largely regulated by viral envelope sequence. We previously reported that the defective doughnut-shaped particles produced from a persistently infected cell clone, named L-2, obtained from human CD4+ T-cell line MT-4 that was persistently infected with HIV-1 LAI strain, efficiently form particle-mediated syncytia with uninfected human CD4+ T-cell line, MOLT-4. Here, we prepared a molecular clone (pL2) containing the L-2 provirus to characterize the viral genetic region contributing to this activity to form particle-mediated syncytia. Several recombinants were constructed with pNL4-3 by replacing the pL2-derived region including full-length env. Characterization of the particles obtained by transfection with these recombinant clones confirmed that pL2-derived env carried the particle-mediated syncytia formation activity. It is noteworthy that the pL2-derived env region could also contribute to enhancement of infectivity in CD4+ T-cell lines as well as primary peripheral blood mononuclear cells (PBMCs). Thus, the HIV-1 particle-mediated syncytium formation activity could also contribute to the enhancement of HIV-1 infectivity.
1型人类免疫缺陷病毒（HIV-1）的感染及后续复制率会影响其致病性。HIV-1感染的初始阶段很大程度上受病毒包膜序列调控。我们之前报道过，从持续感染HIV-1 LAI毒株的人CD4+ T细胞系MT-4中获得的一个持续感染细胞克隆（命名为L-2）产生的有缺陷的甜甜圈状颗粒，能与未感染的人CD4+ T细胞系MOLT-4高效形成颗粒介导的多核巨细胞。在此，我们制备了一个包含L-2前病毒的分子克隆（pL2），以表征对这种形成颗粒介导的多核巨细胞活性有贡献的病毒基因区域。通过用包括全长env在内的pL2衍生区域替换pNL4-3构建了几个重组体。对用这些重组克隆转染获得的颗粒进行表征证实，pL2衍生的env具有颗粒介导的多核巨细胞形成活性。值得注意的是，pL2衍生的env区域也有助于增强在CD4+ T细胞系以及原代外周血单核细胞（PBMC）中的感染性。因此，HIV-1颗粒介导的多核巨细胞形成活性也可能有助于增强HIV-1的感染性。
