Biological and physical characterization of the X4 HIV-1 suppressive factor secreted by LPS-stimulated human macrophages.

Biological and physical characterization of the X4 HIV-1 suppressive factor secreted by LPS-stimulated human macrophages.
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LPS 刺激的人类巨噬细胞分泌的 X4 HIV-1 抑制因子的生物学和物理特征。

DOI:
10.1016/j.virol.2009.04.005
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发表时间:
2009
期刊:
影响因子:
3.7
通讯作者:
Verani,Alessia
Verani,Alessia
中科院分区:
医学3区
文献类型:
--
作者:
Mikulak,Joanna;Gianolini,Monica;Versmisse,Pierre;Pancino,Gianfranco;Lusso,Paolo;Verani,Alessia

文献摘要

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LPS刺激的巨噬细胞释放可溶性因子,抑制CD 4 +T淋巴细胞和巨噬细胞中的HIV-1感染。这些抑制因子包括CCR 5配体RANTES、MIP-1α和MIP-1β,它们选择性地阻断R5 HIV-1毒株,以及一种尚未鉴定的对X4 HIV-1毒株具有活性的因子,我们将其命名为可溶性巨噬细胞源性抗HIV因子(MIFE)。在这里,我们使用X4 HIV-1菌株作为特异性探针,在没有CCR 5结合趋化因子的混杂作用的情况下,研究MIBI的生物学和物理特性。我们表明,Meso具有广泛的作用,因为它可以阻止不同基因亚型的HIV-1菌株的感染。MSTK对热和蛋白酶K处理敏感,并且似乎在MDM内预先形成,因为它在LPS刺激后迅速释放,并且其产生对蛋白质新合成的抑制剂放线菌酮不敏感。不同试验的收敛结果表明,Mexican主要在病毒进入水平起作用。最后,MRF不同于几种已知的具有抗HIV-1活性的细胞因子,包括IL-10、IL-12、IL-16、IFN-γ和α-防御素。的生物学和物理特性的Mesophila可能有助于设计有效的新策略,其识别。
LPS-stimulated macrophages release soluble factors that inhibit HIV-1 infection in both CD4+T lymphocytes and macrophages. These inhibitory factors include the CCR5 ligands RANTES, MIP-1α and MIP-1β, which selectively block R5 HIV-1 strains, and a still unidentified factor with activity against X4 HIV-1 strains that we designate soluble macrophage-derived anti-HIV factor (MDAF). Here, we used X4 HIV-1 strains as specific probes to investigate the biological and physical characteristics of MDAF without the confounding effect of CCR5-binding chemokines. We show that MDAF has a broad spectrum of action, as it blocks infection by HIV-1 strains of different genetic subtypes. MDAF is sensitive to heat and proteinase K treatment, and it appears to be preformed within MDM, in that it is rapidly released upon LPS stimulation and its production is insensitive to cycloheximide, an inhibitor of protein neosynthesis. The convergent results of different assays indicate that MDAF acts primarily at the level of viral entry. Finally, MDAF is distinct from several known cytokines that possess anti-HIV-1 activity, including IL-10, IL-12, IL-16, IFN-γ and α-defensins. The biological and physical characterization of MDAF may be instrumental in devising effective new strategies for its identification.