Influenza viral membrane fusion is sensitive to sterol concentration but surprisingly robust to sterol chemical identity.
Influenza viral membrane fusion is sensitive to sterol concentration but surprisingly robust to sterol chemical identity.
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DOI：
10.1038/srep29842
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发表时间：
2016-07-19
影响因子：
4.6
通讯作者：
Kasson PM
中科院分区：
文献类型：
--
作者：
Zawada KE;Wrona D;Rawle RJ;Kasson PM
流感病毒体相对于它们从中出芽的质膜而言富含胆固醇。先前的工作表明，流感病毒和合成脂质体之间的融合对病毒或靶膜中胆固醇的量敏感。在这里，我们测试所需的胆固醇，以促进流感病毒融合的化学性质，取代胆固醇与其他固醇和测定病毒融合动力学。我们发现，流感病毒与脂质体的融合对固醇化学身份是令人惊讶的稳健的，对于任何测试的固醇，在靶膜中显示对固醇身份没有显著依赖性。在病毒膜中，羊毛甾醇稍微减缓融合，而极性甾醇产生更明显的减缓和抑制融合。没有其他测试的甾醇显示出融合率的显著扰动，包括先前显示出改变膜弯曲模量或相行为的甾醇。虽然融合率取决于病毒胆固醇，但它们因此不需要胆固醇支持液-液相共存的能力。使用电子冷冻显微镜，我们进一步发现，甾醇依赖的变化，血凝素在病毒膜的空间图案不需要液-液相共存。因此，我们推测，在病毒包膜中的局部甾醇-血凝素相互作用可能控制融合的限速步骤。
Influenza virions are enriched in cholesterol relative to the plasma membrane from which they bud. Previous work has shown that fusion between influenza virus and synthetic liposomes is sensitive to the amount of cholesterol in either the virus or the target membrane. Here, we test the chemical properties of cholesterol required to promote influenza fusion by replacing cholesterol with other sterols and assaying viral fusion kinetics. We find that influenza fusion with liposomes is surprisingly robust to sterol chemical identity, showing no significant dependence on sterol identity in target membranes for any of the sterols tested. In the viral membrane, lanosterol slowed fusion somewhat, while polar sterols produced a more pronounced slowing and inhibition of fusion. No other sterols tested showed a significant perturbation in fusion rates, including ones previously shown to alter membrane bending moduli or phase behavior. Although fusion rates depend on viral cholesterol, they thus do not require cholesterol’s ability to support liquid-liquid phase coexistence. Using electron cryo-microscopy, we further find that sterol-dependent changes to hemagglutinin spatial patterning in the viral membrane do not require liquid-liquid phase coexistence. We therefore speculate that local sterol-hemagglutinin interactions in the viral envelope may control the rate-limiting step of fusion.