Exogenous and endogenous hyaluronic acid reduces HIV infection of CD4(+) T cells.

Exogenous and endogenous hyaluronic acid reduces HIV infection of CD4(+) T cells.
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DOI:
10.1038/icb.2014.50
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发表时间:
2014-10
影响因子:
4
通讯作者:
Wong, Joseph K.
Wong, Joseph K.
中科院分区:
医学3区
文献类型:
--
作者:
Li, Peilin;Fujimoto, Katsuya;Bourguingnon, Lilly;Yukl, Steven;Deeks, Steven;Wong, Joseph K.

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预防艾滋病毒的粘膜传播对遏制艾滋病毒流行至关重要。需要防止粘膜传播的新方法。透明质酸(HA)是粘膜的主要细胞外组分,也是细胞表面受体CD44的主要配体。CD44增强了HIV感染CD4+ T细胞,但HA在此过程中的作用尚不清楚。为了研究这一点,用CD44(HIVCD44)或不用CD44(HIVmock)产生病毒体。外源性HA以CD44依赖性方式减少未刺激的CD4+ T细胞的HIV感染。相反,透明质酸酶介导的细胞表面内源性HA的减少增强了HIV与未受刺激的CD4+ T细胞的结合和感染。外源性HA治疗减少了HIV感染过程中CD4+ T细胞上通过CD44激活的蛋白激酶C α。这些结果揭示了HA在HIV与CD4+ T细胞相互作用过程中的新作用,这些作用可能与粘膜HIV传播有关,并可作为预防HIV感染的未来策略。
Preventing mucosal transmission of HIV is critical to halting the HIV epidemic. Novel approaches to preventing mucosal transmission are needed. Hyaluronic acid (HA) is a major extracellular component of mucosa and the primary ligand for the cell surface receptor CD44. CD44 enhances HIV infection of CD4+ T cells, but the role of HA in this process is not clear. To study this, virions were generated with CD44 (HIVCD44) or without CD44 (HIVmock). Exogenous HA reduced HIV infection of unstimulated CD4+ T cells in a CD44-dependent manner. Conversely, hyaluronidase-mediated reduction of endogenous HA on the cell surface enhanced HIV binding to and infection of unstimulated CD4+ T cells. Exogenous HA treatment reduced activation of protein kinase C alpha via CD44 on CD4+ T cells during infection with HIVCD44. These results reveal new roles for HA during the interaction of HIV with CD4+ T cells that may be relevant to mucosal HIV transmission and could be exploitable as a future strategy to prevent HIV infection.
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