Stearoyl-CoA desaturase-1 is required for flavivirus RNA replication
Stearoyl-CoA desaturase-1 is required for flavivirus RNA replication
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DOI：
10.1016/j.antiviral.2019.03.002
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发表时间：
2019-05-01
影响因子：
7.6
通讯作者：
Takasaki, Tomohiko
中科院分区：
文献类型：
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作者：
Hishiki, Takayuki;Kato, Fumihiro;Takasaki, Tomohiko
登革病毒（DENV）是最流行的人类节肢动物传播的病毒，并在全球范围内引起严重的问题，主要在热带和亚热带地区。然而，目前还没有针对DENV感染的特异性抗病毒药物。我们和其他人最近报道了硬脂酰辅酶A去饱和酶-1（SCD 1）抑制剂对丙型肝炎病毒复制的有效抑制作用。在这项研究中，我们研究了SCD 1对DENV复制的影响。我们发现，SCD 1抑制剂（MK 8245和#1716）以剂量依赖性方式显著抑制DENV复制，而无细胞毒性。针对所有四种DENV血清型和其他黄病毒（包括寨卡病毒和日本脑炎病毒）观察到这种抗DENV功效。使用DENV的亚基因组复制子系统来证实SCD 1抑制剂抑制病毒RNA复制。有趣的是，即使在SCD 1抑制剂存在下，外源性补充不饱和脂肪酸也导致DENV滴度的恢复，表明脂肪酸生物合成有助于DENV基因组复制。这些结果表明，SCD 1是一种新的宿主因子所需的登革病毒复制，和SCD 1抑制剂是一个潜在的候选人，用于治疗登革热。
Dengue virus (DENV) is the most prevalent human arthropod-borne virus and causes severe problems worldwide, mainly in tropical and sub-tropical regions. However, there is no specific antiviral drug against DENV infection. We and others recently reported that stearoyl-CoA desaturase-1 (SCD1) inhibitor showed potent suppression of hepatitis C virus replication. In this study, we examined the impact of SCD1 on DENV replication. We found that SCD1 inhibitors (MK8245 and #1716) dramatically suppressed DENV replication in a dose dependent manner without cytotoxicity. This anti-DENV efficacy was observed against all four DENV serotypes and other flaviviruses, including Zika virus and Japanese encephalitis virus. A subgenomic replicon system of DENV was used to confirm that SCD1 inhibitor suppressed viral RNA replication. Interestingly, exogenous supplementation of unsaturated fatty acids resulted in recovery of the DENV titer even in the presence of SCD1 inhibitor, suggesting that fatty acid biosynthesis contributes to DENV genome replication. These findings indicate that SCD1 is a novel host factor required for DENV replication, and SCD1 inhibitor is a potential candidate for treating dengue fever.