Abstract：
Several flaviviruses such as Hepatitis C virus, West Nile virus, Dengue virus and Japanese Encephalitis virus exploit the raft platform to enter host cells whereas the involvement of lipid rafts in Zika virus-host cell interaction has not yet been demonstrated. Zika virus disease is caused by a flavivirus transmitted by Aedes spp. Mosquitoes, although other mechanisms such as blood transfusion, sexual and maternal-fetal transmission have been demonstrated. Symptoms are generally mild, such as fever, rash, joint pain and conjunctivitis, but neurological complications, including Guillain-Barré syndrome, have been associated to this viral infection. During pregnancy, it can cause microcephaly and other congenital abnormalities in the fetus, as well as pregnancy complications, representing a serious health threat. In this study, we show for the first time that Zika virus employs cell membrane lipid rafts as a portal of entry into Vero cells. We previously demonstrated that the antifungal drug Amphotericin B (AmphB) hampers a microbe-host cell interaction through the disruption of lipid raft architecture. Here, we found that Amphotericin B by the same mechanism of action inhibits both Zika virus cell entry and replication. These data encourage further studies on the off-label use of Amphotericin B in Zika virus infections as a new and alternate antiviral therapy.
摘要：
几种黄病毒，如丙型肝炎病毒，西尼罗河病毒,登革热病毒和日本脑炎病毒利用移植物平台进入宿主细胞，而脂筏参与寨卡病毒-宿主细胞相互作用尚未得到证实。寨卡病毒病是由伊蚊传播的黄病毒引起的。蚊子,尽管其他机制如输血，已经证明了性传播和母婴传播。症状一般轻微,比如发烧，皮疹,关节痛和结膜炎,但神经系统并发症,包括格林-巴利综合征,与这种病毒感染有关。在怀孕期间,它会导致胎儿的小头畸形和其他先天性畸形，以及妊娠并发症，代表着严重的健康威胁。在这项研究中,我们首次证明寨卡病毒利用细胞膜脂筏作为进入Vero细胞的入口。我们先前证明了抗真菌药物两性霉素B（AmphB）通过破坏脂筏结构来阻碍微生物与宿主细胞的相互作用。这里,我们发现两性霉素B通过相同的作用机制抑制寨卡病毒细胞的进入和复制。这些数据鼓励进一步研究在寨卡病毒感染中使用两性霉素B作为一种新的和替代的抗病毒疗法。
