Gp120 V3-dependent impairment of R5 HIV-1 infectivity due to virion-incorporated CCR5
Gp120 V3-dependent impairment of R5 HIV-1 infectivity due to virion-incorporated CCR5
复制标题
DOI：
10.1074/jbc.m705298200
复制
发表时间：
2007-12-21
影响因子：
4.8
通讯作者：
Yusa, Keisuke
中科院分区：
文献类型：
--
作者：
Monde, Kazuaki;Maeda, Yosuke;Yusa, Keisuke
R5人类免疫缺陷病毒1型(HIV-1)进入靶细胞需要包膜糖蛋白gp120与受体CD4和辅受体CCR5的顺序相互作用。我们研究了来自HIV-1(JR-flan)文库的45个R5病毒克隆的复制，该文库在gp120 V3环中携带0-10个随机氨基酸替换。结果发现，6.7%(3/45)的病毒在高水平表达CCR5的PM1/CCR5细胞中表现出复制抑制，是低水平表达CCR5的PM1细胞的10倍。在HIV-1(V3L#08)中，复制抑制与进入事件和病毒生产无关，但与新生后代病毒的传染性显著降低有关。从感染的PM1/CCR5细胞产生的HIV-1(V3L#08)，98%被抗CCR5单抗T21/8免疫沉淀，而其他感染性病毒只有部分沉淀，这表明大量的CCR5掺入病毒粒子中导致了HIV-1(V3L#08)病毒感染性的降低。结果证明了CCR5对HIV-1复制的另一种影响的含义。
Entry of R5 human immunodeficiency virus type 1 (HIV-1) into target cells requires sequential interactions of the envelope glycoprotein gp120 with the receptor CD4 and the coreceptor CCR5. We investigated replication of 45 R5 viral clones derived from the HIV-1(JR-FLan) library carrying 0 - 10 random amino acid substitutions in the gp120 V3 loop. It was found that 6.7% (3/45) of the viruses revealed >= 10-fold replication suppression in PM1/CCR5 cells expressing high levels of CCR5 compared with PM1 cells expressing low levels of CCR5. In HIV-1(V3L#08), suppression of replication was not associated with entry events and viral production but with a marked decrease in infectivity of nascent progeny virus. HIV-1(V3L#08), generated from infected PM1/CCR5 cells, was 98% immunoprecipitated by anti-CCR5 monoclonal antibody T21/8, whereas the other infectious viruses were only partially precipitated, suggesting that incorporation of larger amounts of CCR5 into the virions caused impairment of viral infectivity in HIV-1(V3L#08). The results demonstrate the implications of an alternative influence of CCR5 on HIV-1 replication.