Enhancement of human immunodeficiency virus type 1 infection by the CC-chemokine RANTES is independent of the mechanism of virus-cell fusion

Enhancement of human immunodeficiency virus type 1 infection by the CC-chemokine RANTES is independent of the mechanism of virus-cell fusion
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DOI:
10.1128/jvi.73.1.684-694.1999
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发表时间:
1999-01-01
影响因子:
5.4
通讯作者:
Trkola, A
Trkola, A
中科院分区:
医学2区
文献类型:
--
作者:
Gordon, CJ;Muesing, MA;Trkola, A

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我们研究了CC-趋化因子对人类免疫缺陷病毒1型(HIV-1)感染的影响,重点是RANTES引起的感染性增强。高RANTES浓度增加了使用CXC趋化因子受体3进入的HIV-1分离株的感染性。然而,RANTES可以对通过CC-趋化因子受体5(CCRS)进入的巨噬细胞病毒具有类似的增强作用,尽管与病毒结合至相同的受体。此外,RANTES增强了HIV-1假型与小鼠白血病病毒或水泡性口炎病毒的包膜糖蛋白的感染性,表明增强的机制是独立的病毒-细胞融合的途径。RANTES的增强作用不通过CCR 5或其他已知的趋化因子受体介导,也不被MIP-1 α或MIP-1 β模拟。N-末端修饰的衍生物氨氧基戊烷RANTES(AOP-RANTES)通过CCRS有效地抑制HIV-1感染,但通过增强病毒感染性来模拟RANTES。有两种增强机制:一种是当靶细胞用RANTES(或AOP-RANTES)预处理数小时时明显,另一种是当在病毒-细胞吸收过程中加入RANTES(或AOP-RANTES)时明显。我们认为,第一种机制与RANTES的细胞活化有关,而第二种机制是病毒粒子附着靶细胞的增加。
We have studied the effects of CC-chemokines on human immunodeficiency virus type 1 (HIV-1) infection, focusing on the infectivity enhancement caused by RANTES. High RANTES concentrations increase the infectivity of HIV-1 isolates that use CXC-chemokine receptor 3 for entry. However, RANTES can have a similar enhancing effect on macrophagetropic viruses that enter via CC-chemokine receptor 5 (CCRS), despite binding to the same receptor as the virus. Furthermore, RANTES enhances the infectivity of HIV-1 pseudotyped with the envelope glycoprotein of murine leukemia virus or vesicular stomatitis virus, showing that the mechanism of enhancement is independent of the route of virus-cell fusion. The enhancing effects of RANTES are not mediated via CCR5 or other known chemokine receptors and are not mimicked by MIP-1 alpha or MIP-1 beta. The N-terminally modified derivative aminooxypentane RANTES (AOP-RANTES) efficiently inhibits HIV-1 infection via CCRS but otherwise mimics RANTES by enhancing viral infectivity. There are two mechanisms of enhancement: one apparent when target cells are pretreated with RANTES (or AOP-RANTES) for several hours, and the other apparent when RANTES (or AOP-RANTES) is added during virus-cell absorption. We believe that the first mechanism is related to cellular activation by RANTES, whereas the second is an increase in virion attachment to target cells.