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.
复制标题
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
复制
发表时间:
2009
期刊:
影响因子:
3.7
通讯作者:
Verani,Alessia
中科院分区:
文献类型:
--
作者:
Mikulak,Joanna;Gianolini,Monica;Versmisse,Pierre;Pancino,Gianfranco;Lusso,Paolo;Verani,Alessia
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.