Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China.
Insect Molecular Genetics and Biotechnology, National Centre for Scientific Research Demokritos, Institute of Biosciences and Applications, Athens, Greece.
Front Immunol. 2022 May 23;13:906738. doi: 10.3389/fimmu.2022.906738. eCollection 2022.
Silent information regulators (Sirtuins) belong to the family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (HDACs) that have diverse functions in cells. Mammalian Sirtuins have seven isoforms (Sirt1-7) which have been found to play a role in viral replication. However, Sirtuin members of insects are very different from mammals, and the function of insect Sirtuins in regulating virus replication is unclear. The silkworm, , as a model species of Lepidoptera, is also an important economical insect. nucleopolyhedrovirus (BmNPV) is a major pathogen that specifically infects silkworms and causes serious losses in the sericulture industry. Here, we used the infection of the silkworm by BmNPV as a model to explore the effect of Sirtuins on virus replication. We initially knocked down all silkworm Sirtuins, and then infected with BmNPV to analyze its replication. Sirt2 and Sirt5 were found to have potential antiviral functions in the silkworm. We further confirmed the antiviral function of silkworm Sirt5 through its effects on viral titers during both knockdown and overexpression experiments. Additionally, Suramin, a Sirt5 inhibitor, was found to promote BmNPV replication. In terms of molecular mechanism, it was found that silkworm Sirt5 might promote the immune pathway mediated by Relish, thereby enhancing the host antiviral response. This study is the first to explore the role of Sirtuins in insect-virus interactions, providing new insights into the functional role of members of the insect Sirtuin family.
沉默信息调节因子（Sirtuins）属于烟酰胺腺嘌呤二核苷酸（NAD）依赖性组蛋白去乙酰化酶（HDACs）家族，在细胞中具有多种功能。哺乳动物 Sirtuins 有 7 种同工型（Sirt1-7），已发现它们在病毒复制中发挥作用。然而，昆虫的 Sirtuin 成员与哺乳动物非常不同，昆虫 Sirtuins 在调节病毒复制中的功能尚不清楚。家蚕 作为鳞翅目昆虫的模式物种，也是一种重要的经济昆虫。 核型多角体病毒（BmNPV）是一种专门感染家蚕并导致养蚕业严重损失的主要病原体。在这里，我们使用 BmNPV 感染家蚕作为模型来探索 Sirtuins 对病毒复制的影响。我们最初敲低了所有家蚕 Sirtuins，然后感染 BmNPV 来分析其复制。发现 Sirt2 和 Sirt5 在蚕中具有潜在的抗病毒功能。我们通过在敲低和过表达实验中对病毒滴度的影响进一步证实了家蚕 Sirt5 的抗病毒功能。此外，发现 Sirt5 抑制剂苏拉明促进了 BmNPV 的复制。就分子机制而言，发现家蚕 Sirt5 可能通过激活 Relish 介导的免疫途径来促进宿主抗病毒反应。这项研究首次探索了 Sirtuins 在昆虫-病毒相互作用中的作用，为昆虫 Sirtuin 家族成员的功能作用提供了新的见解。
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