Coxsackievirus A16 (CA16) is one of predominant Enterovirus that possesses high pathogenicity. Lipid rafts, as cholesterol ­ and sphingolipid ­ enriched membrane nanodomains, are involved into many aspects of the virus life cycle. Our previous study found that lipid rafts integrity was essential for CA16 replication, but how lipid rafts regulate CA16 replication through activating downstream signaling remains largely unknown. Thus, in this study, we revealed that lipid rafts were required for activation of PI3K/Akt signaling at early stage of CA16 infection. Treatment with wortmannin significantly reduced the expression of virus protein, indicating PI3K/Akt signaling was beneficial for early stage of virus infection. In addition, lipid rafts integrity was also indispensable for PI3K/Akt activation during the late stage of CA16 infection, which played critical functions in mediating sterol regulatory element-binding proteins 1 (SREBP1) maturation. Whereas, over-expression of SREBP1 exhibited inhibition on virus replication, suggesting that PI3K/Akt signaling and SREBP1 might positively and negatively influence virus replication in two different stage of infection, respectively. Taken together, our study demonstrates an important role for the lipid raft-associated PI3K/Akt/SREBP1 signaling in modulating CA16 replication, which will deepen our understanding mechanism of CA16 infection.

柯萨奇病毒A16（CA16）是主要的肠病毒之一具有高致病性。作为胆固醇和鞘脂富集的膜纳米域的脂质筏参与了病毒生命周期的许多方面。我们以前的研究发现脂质筏的完整性对于CA16复制至关重要，但是脂质筏如何通过激活下游信号传导调节CA16复制仍然是未知的。因此，在这项研究中，我们发现脂质筏是CA16感染早期激活PI3K / Akt信号传导所必需的。用渥曼青霉素处理显着降低了病毒蛋白的表达，表明PI3K / Akt信号传导对病毒感染的早期阶段是有益的。此外，在CA16感染的晚期，脂质筏的完整性对于PI3K / Akt激活也是必不可少的，在介导固醇调节元件结合蛋白1（SREBP1）成熟中起着关键作用。然而，SREBP1的过表达表现出对病毒复制的抑制作用，这表明PI3K / Akt信号和SREBP1可能分别在感染的两个不同阶段对病毒复制产生正向和负向影响。两者合计，我们的研究表明脂质筏相关的PI3K / Akt / SREBP1信号在调节CA16复制中起重要作用，这将加深我们对CA16感染的理解机制。