Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3000, Australia;
Institute for Vector Borne Disease, Monash University, Clayton, Melbourne, VIC 3168, Australia.
Proc Natl Acad Sci U S A. 2020 Sep 29;117(39):24475-24483. doi: 10.1073/pnas.1914814117. Epub 2020 Sep 10.
-infected mosquitoes are refractory to flavivirus infections, but the role of lipids in -mediated virus blocking remains to be elucidated. Here, we use liquid chromatography mass spectrometry to provide a comprehensive picture of the lipidome of cells infected with only, either dengue or Zika virus only, and -infected cells superinfected with either dengue or Zika virus. This approach identifies a class of lipids, acyl-carnitines, as being down-regulated during infection. Furthermore, treatment with an acyl-carnitine inhibitor assigns a crucial role for acyl-carnitines in the replication of dengue and Zika viruses. In contrast, depletion of acyl-carnitines increases density while addition of commercially available acyl-carnitines impairs production. Finally, we show an increase in flavivirus infection of -infected cells with the addition of acyl-carnitines. This study uncovers a previously unknown role for acyl-carnitines in this tripartite interaction that suggests an important and broad mechanism that underpins -mediated pathogen blocking.
受感染的蚊子对黄病毒感染具有抗性，但脂质在介导的病毒阻断中的作用仍有待阐明。在这里，我们使用液相色谱-质谱联用技术对仅感染登革热病毒或寨卡病毒的细胞以及再次感染登革热病毒或寨卡病毒的感染细胞的脂质组进行了全面描绘。该方法鉴定出一类脂质，酰基辅酶 A，在感染期间下调。此外，用酰基辅酶 A 抑制剂处理赋予酰基辅酶 A 在登革热和寨卡病毒复制中的关键作用。相比之下，酰基辅酶 A 的消耗增加了密度，而商业上可用的酰基辅酶 A 的添加则损害了的产生。最后，我们发现添加酰基辅酶 A 会增加感染细胞的黄病毒感染。这项研究揭示了酰基辅酶 A 在这种三分体相互作用中的一个以前未知的作用，表明了一个重要的、广泛的机制，为介导的病原体阻断提供了支持。
