Effects of IFNα on late stages of HIV-1 replication cycle
Effects of IFNα on late stages of HIV-1 replication cycle
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DOI：
10.1016/s0300-9084(99)80028-5
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发表时间：
1998-08-01
期刊：
影响因子：
3.9
通讯作者：
Capobianchi, MR
中科院分区：
文献类型：
--
作者：
Dianzani, F;Castilletti, C;Capobianchi, MR
IFN α可导致慢性感染的单核细胞样U937细胞中HIV-1表达的适度降低。然而，细胞相关和脱落的病毒p24抗原之间的比例被改变，细胞相关部分剂量依赖性地增强IFN。此外，观察到细胞相关和脱落物质的感染性显著降低。IFN-处理的细胞的透射电子显微镜显示病毒组装被强烈抑制，与形态改变（泪滴形）的病毒颗粒的生产。gag蛋白的蛋白水解处理在IFN处理的培养物中似乎是正常的。然而，从IFN处理的细胞脱落的病毒粒子显示出病毒特异性gp 120和细胞衍生的ICAM-1的病毒包膜的掺入显着减少。此外，这些颗粒显示出与CD 4+靶细胞结合的能力显著降低，至少部分地解释了观察到的感染性降低。总之，这些数据表明，在慢性感染的细胞中，IFN α可以通过抑制病毒组装和释放以及通过降低脱落病毒粒子的感染性来影响HIV-1复制的晚期阶段。后一种效果似乎是由于，至少部分地，改变掺入的表面糖蛋白和有缺陷的颗粒形成。受损的gp 120掺入和改变HIV-1病毒粒子的形态发生之间的关系正在调查中。(C)法国生物化学与分子生物学协会/爱思唯尔，巴黎。
IFN alpha causes a modest reduction of HIV-1 expression in chronically infected monocytoid U937 cells. However, the ratio between cell-associated and shed viral p24 antigen is altered, being the cell-associated fraction dose-dependently enhanced by IFN. Furthermore, a significant decrease of infectivity of both cell-associated and shed material is observed. Transmission electron microscopy of IFN-treated cells revealed virus assembly being strongly inhibited, with the production of morphologically altered (tear-drop shaped) virus particles. Proteolytic processing of gag proteins appeared to be normal in IFN-treated cultures. However, virions shed from IFN-treated cells showed a markedly reduced incorporation of virus-specific gp120 and cell-derived ICAM-1 by the virus envelope. Additionally, these particles showed a significantly decreased ability to become bound to CD4+ target cells, accounting for, at least in part, the observed decrease of infectivity. Taken together the data suggest that, in chronically infected cells, IFN alpha can affect late stages of HIV-1 replication, by inhibiting virus assembly and release, and by reducing the infectivity of shed virions. The latter effect seems to be due, at least in part, to altered incorporation of surface glycoproteins and defective particle formation. The relationship between impaired gp120 incorporation and altered morphogenesis of HIV-1 virions is under investigation. (C) Societe francaise de biochimie et biologie moleculaire/Elsevier, Paris.