TY  - JOUR
AU  - Manokaran, G
AU  - Flores, HA
AU  - Dickson, CT
AU  - Narayana, VK
AU  - Kanojia, K
AU  - Dayalan, S
AU  - Tull, D
AU  - McConville, MJ
AU  - Mackenzie, JM
AU  - Simmons, CP
Y2  - 2020/11/17
Y1  - 2020/09/29
SN  - 0027-8424
UR  - http://hdl.handle.net/11343/251564
AB  - Wolbachia-infected mosquitoes are refractory to flavivirus infections, but the role of lipids in Wolbachia-mediated virus blocking remains to be elucidated. Here, we use liquid chromatography mass spectrometry to provide a comprehensive picture of the lipidome of Aedes aegypti (Aag2) cells infected with Wolbachia only, either dengue or Zika virus only, and Wolbachia-infected Aag2 cells superinfected with either dengue or Zika virus. This approach identifies a class of lipids, acyl-carnitines, as being down-regulated during Wolbachia 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 Wolbachia density while addition of commercially available acyl-carnitines impairs Wolbachia production. Finally, we show an increase in flavivirus infection of Wolbachia-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 Wolbachia-mediated pathogen blocking.
LA  - English
PB  - NATL ACAD SCIENCES
T1  - Modulation of acyl-carnitines, the broad mechanism behind Wolbachia-mediated inhibition of medically important flaviviruses in Aedes aegypti
DO  - 10.1073/pnas.1914814117
IS  - Proceedings of the National Academy of Sciences of USA
VL  - 117
IS  - 39
SP  - 24475-24483
L1  - /bitstream/handle/11343/251564/PMC7533870.pdf?sequence=1&isAllowed=y
ER  -