Orsay Virus Infection of Caenorhabditis elegans Is Modulated by Zinc and Dependent on Lipids.
Orsay Virus Infection of Caenorhabditis elegans Is Modulated by Zinc and Dependent on Lipids.
复制标题
DOI：
10.1128/jvi.01211-22
复制
发表时间：
2022-11-23
影响因子：
5.4
通讯作者：
中科院分区：
文献类型：
--
作者：
病毒利用宿主脂质来促进病毒生命周期，但其如何调节仍不清楚。锌是生命的关键元素，很少有研究将锌与脂质稳态联系起来。我们证明奥赛病毒对秀丽隐杆线虫的感染依赖于脂质，并且脂质生物合成的主调节因子 sbp-1 的突变使奥赛病毒 RNA 水平降低了约 236 倍。通过饮食补充 fat-6/fat-7 下游的脂质可以挽救病毒感染。 sur-7 编码的锌转运蛋白突变可抑制 sbp-1 的脂质缺陷，也挽救了奥赛病毒感染。此外，通过 sbp-1 突变体中的化学螯合降低锌水平也增加了脂质并挽救了奥赛病毒 RNA 水平。最后，通过膳食补充剂增加锌水平导致病毒 RNA 减少约 1,620 倍。这些发现为病毒感染所需的锌和宿主脂质之间的关键相互作用提供了见解。重要性 奥赛病毒是唯一已知的秀丽隐杆线虫天然病毒病原体，它与人类共享许多进化上保守的途径。我们利用线虫强大的遗传易处理性来表征锌、脂质和病毒感染之间的新型相互作用。 sbp-1突变动物中奥赛病毒复制的抑制（通过脂质消耗来解释）可以通过遗传和药理学方法来挽救，该方法减少突变动物中的锌积累并挽救脂质水平。有趣的是，sbp-1 的人类直系同源物 srebp-1 据报道在病毒感染中发挥作用，并且锌已被证明可以抑制多种病毒的病毒复制。然而，锌的作用机制尚不清楚。这些结果表明，锌介导的脂质调节可能在哺乳动物病毒感染过程中发挥相关作用。
Viruses utilize host lipids to promote the viral life cycle, but much remains unknown as to how this is regulated. Zinc is a critical element for life, and few studies have linked zinc to lipid homeostasis. We demonstrated that Caenorhabditis elegans infection by Orsay virus is dependent upon lipids and that mutation of the master regulator of lipid biosynthesis, sbp-1, reduced Orsay virus RNA levels by ~236-fold. Virus infection could be rescued by dietary supplementation with lipids downstream of fat-6/fat-7. Mutation of a zinc transporter encoded by sur-7, which suppresses the lipid defect of sbp-1, also rescued Orsay virus infection. Furthermore, reducing zinc levels by chemical chelation in the sbp-1 mutant also increased lipids and rescued Orsay virus RNA levels. Finally, increasing zinc levels by dietary supplementation led to an ~1,620-fold reduction in viral RNA. These findings provide insights into the critical interactions between zinc and host lipids necessary for virus infection. IMPORTANCE Orsay virus is the only known natural virus pathogen of Caenorhabditis elegans, which shares many evolutionarily conserved pathways with humans. We leveraged the powerful genetic tractability of C. elegans to characterize a novel interaction between zinc, lipids, and virus infection. Inhibition of the Orsay virus replication in the sbp-1 mutant animals, explained by the lipid depletion, can be rescued by a genetic and pharmacological approach that reduces the zinc accumulation and rescues the lipid levels in this mutant animal. Interestingly, the human ortholog of sbp-1, srebp-1, has been reported to play a role for virus infection, and zinc has been shown to inhibit the virus replication of multiple viruses. However, the mechanism through which zinc is acting is not well understood. These results suggest that the lipid regulation mediated by zinc may play a relevant role during mammalian virus infection.
登录
查看更多内容
秀丽隐杆线虫中不饱和脂肪酸组成的遗传调节。
影响因子：
4.5
作者：
Brock, Trisha J.;Browse, John;Watts, Jennifer L.
通讯作者：
Watts, Jennifer L.
影响因子：
5.9
作者：
通讯作者：
--
影响因子：
13.5
作者：
BODE, JC;HANISCH, P;BODE, C
通讯作者：
BODE, C
影响因子：
4.8
作者：
Fenstermacher, Katherine J.;DeStefano, Jeffrey J.
通讯作者：
DeStefano, Jeffrey J.
Caenorhabdision秀丽隐杆线虫中的删除多态性RIG-I同源物可以禁用病毒RNA DICING和抗病毒免疫。
影响因子：
7.7
作者：
Ashe A;Bélicard T;Le Pen J;Sarkies P;Frézal L;Lehrbach NJ;Félix MA;Miska EA
通讯作者：
Miska EA