Functional organization of the HIV lipid envelope.

Functional organization of the HIV lipid envelope.
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DOI:
10.1038/srep34190
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发表时间:
2016-09-28
期刊:
影响因子:
4.6
通讯作者:
Nieva JL
Nieva JL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Huarte N;Carravilla P;Cruz A;Lorizate M;Nieto-Garai JA;Kräusslich HG;Pérez-Gil J;Requejo-Isidro J;Nieva JL

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人类免疫缺陷病毒 1 型 (HIV-1) 膜的化学成分对于融合和进入靶细胞至关重要,这表明有效感染可能需要保留功能性脂质双层组织。 HIV-1从宿主细胞质膜富含筏型脂质的位点获得其包膜。此外,感染性颗粒在其表面显示氨基磷脂,表明细胞膜代谢产生的小叶间脂质不对称性的消散。通过结合双光子激发劳丹荧光成像和原子力显微镜,我们对从病毒脂质(即从感染性 HIV-1 颗粒中提取)重构的膜的相态获得了前所未有的见解,确定了不同样本在混合物中所起的作用,并表征了膜活性杀病毒剂对膜组织的影响。在确定 HIV-1 膜的脂质堆积和横向异质性的分子基础时,我们的结果可能有助于开发通过扰乱脂质包膜的功能组织而发挥抗病毒活性的化合物。
The chemical composition of the human immunodeficiency virus type 1 (HIV-1) membrane is critical for fusion and entry into target cells, suggesting that preservation of a functional lipid bilayer organization may be required for efficient infection. HIV-1 acquires its envelope from the host cell plasma membrane at sites enriched in raft-type lipids. Furthermore, infectious particles display aminophospholipids on their surface, indicative of dissipation of the inter-leaflet lipid asymmetry metabolically generated at cellular membranes. By combining two-photon excited Laurdan fluorescence imaging and atomic force microscopy, we have obtained unprecedented insights into the phase state of membranes reconstituted from viral lipids (i.e., extracted from infectious HIV-1 particles), established the role played by the different specimens in the mixtures, and characterized the effects of membrane-active virucidal agents on membrane organization. In determining the molecular basis underlying lipid packing and lateral heterogeneity of the HIV-1 membrane, our results may help develop compounds with antiviral activity acting by perturbing the functional organization of the lipid envelope.
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