PDF(Pubmed)
Abstract：
One third of all emerging infectious diseases are vector-borne, with no licensed antiviral therapies available against any vector-borne viruses. Zika virus and Usutu virus are two emerging flaviviruses transmitted primarily by mosquitoes. These viruses modulate different host pathways, including the PI3K/AKT/mTOR pathway. Here, we report the effect on ZIKV and USUV replication of two AKT inhibitors, Miransertib (ARQ-092, allosteric inhibitor) and Capivasertib (AZD5363, competitive inhibitor) in different mammalian and mosquito cell lines. Miransertib showed a stronger inhibitory effect against ZIKV and USUV than Capivasertib in mammalian cells, while Capivasertib showed a stronger effect in mosquito cells. These findings indicate that AKT plays a conserved role in flavivirus infection, in both the vertebrate host and invertebrate vector. Nevertheless, the specific function of AKT may vary depending on the host species. These findings indicate that AKT may be playing a conserved role in flavivirus infection in both, the vertebrate host and the invertebrate vector. However, the specific function of AKT may vary depending on the host species. A better understanding of virus-host interactions is therefore required to develop new treatments to prevent human disease and new approaches to control transmission by insect vectors.
摘要：
所有新出现的传染病中有三分之一是媒介传播的，没有针对任何媒介传播病毒的许可抗病毒疗法。寨卡病毒和Usutu病毒是两种主要由蚊子传播的新兴黄病毒。这些病毒调节不同的宿主途径，包括PI3K/AKT/mTOR通路。这里,我们报道了两种AKT抑制剂对ZIKV和USUV复制的影响，不同哺乳动物和蚊子细胞系中的Miransertib（ARQ-092，变构抑制剂）和Capivasertib（AZD5363，竞争性抑制剂）。在哺乳动物细胞中，Miransertib对ZIKV和USUV的抑制作用强于Capivasertib，而Capivasertib在蚊子细胞中显示出更强的作用。这些发现表明AKT在黄病毒感染中起保守作用。在脊椎动物宿主和无脊椎动物载体中。然而，AKT的特定功能可能因宿主物种而异。这些发现表明，AKT可能在黄病毒感染中发挥保守作用。脊椎动物宿主和无脊椎动物载体。然而,AKT的特定功能可能因宿主物种而异。因此，需要更好地了解病毒与宿主的相互作用，以开发预防人类疾病的新疗法和控制昆虫媒介传播的新方法。
