A critical role for CD63 in HIV replication and infection of macrophages and cell lines.

A critical role for CD63 in HIV replication and infection of macrophages and cell lines.
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DOI:
10.1016/j.virol.2008.06.029
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发表时间:
2008-09-30
期刊:
影响因子:
3.7
通讯作者:
Ferguson, Monique R.
Ferguson, Monique R.
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Hui;Dziuba, Natallia;Friedrich, Brian;von Lindern, Jana;Murray, James L.;Rojo, Daniel R.;Hodge, Thomas W.;O'Brien, William A.;Ferguson, Monique R.

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HIV感染通常涉及Env与CD4和趋化因子辅助受体CCR5或CXCR4的相互作用。支持艾滋病毒复制的其他细胞因素也已确定。我们先前通过抗CD63抗体的预处理抑制巨噬细胞中的HIV感染事件,证明了CD63在早期HIV感染事件中的作用。为了证实HIV复制中对CD63的需求,我们利用CD63特异性的短干扰RNA(SiRNA)降低了CD63的表达,并显示了对巨噬细胞中HIV复制的抑制。令人惊讶的是,CD63 siRNA预处理不仅使CD63的表达沉默了90%,而且还抑制了HIV-1在培养的细胞系(U373-MAGI)中的复制,该细胞系以前被证明对CD63单抗的抑制不敏感。尽管抗CD63抗体以前被证明只在巨噬细胞中抑制早期HIV感染事件,但我们现在显示CD63在巨噬细胞和细胞系中的后来的HIV复制事件中具有潜在的作用。进一步阐明CD63在HIV复制中的作用可能会导致新的治疗化合物的开发。
HIV infection typically involves interaction of Env with CD4 and a chemokine coreceptor, either CCR5 or CXCR4. Other cellular factors supporting HIV replication have also been characterized. We previously demonstrated a role for CD63 in early HIV infection events in macrophages via inhibition by anti-CD63 antibody pretreatment. To confirm the requirement for CD63 in HIV replication, we decreased CD63 expression using CD63-specific short interfering RNAs (siRNA), and showed inhibition of HIV replication in macrophages. Surprisingly, pretreatment with CD63 siRNA not only silenced CD63 expression by 90%, but also inhibited HIV-1 replication in a cultured cell line (U373-MAGI) which had been previously shown to be insensitive to CD63 monoclonal antibody inhibition. Although the anti-CD63 antibody was previously shown to inhibit early HIV infection events only in macrophages, we now show a potential role for CD63 in later HIV replication events in macrophages and cell lines. Further delineation of the role of CD63 in HIV replication may lead to development of novel therapeutic compounds.
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