Host sphingomyelin increases West Nile virus infection in vivo
Flaviviruses, such as the dengue virus and the West Nile virus (WNV), are arthropod-borne viruses that represent a global health problem. The flavivirus lifecycle is intimately connected to cellular lipids. Among the lipids co-opted by flaviviruses, we have focused on SM, an important component of cellular membranes particularly enriched in the nervous system. After infection with the neurotropic WNV, mice deficient in acid sphingomyelinase (ASM), which accumulate high levels of SM in their tissues, displayed exacerbated infection. In addition, WNV multiplication was enhanced in cells from human patients with Niemann-Pick type A, a disease caused by a deficiency of ASM activity resulting in SM accumulation. Furthermore, the addition of SM to cultured cells also increased WNV infection, whereas treatment with pharmacological inhibitors of SM synthesis reduced WNV infection. Confocal microscopy analyses confirmed the association of SM with viral replication sites within infected cells. Our results unveil that SM metabolism regulates flavivirus infection in vivo and propose SM as a suitable target for antiviral design against WNV. © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.
Main Authors: | Martín-Acebes, M. A., Gabandé-Rodríguez, E., García-Cabrero, A. M., Sánchez, M. P., Ledesma, M. D., Sobrino, F., Saiz Calahorra, Juan Carlos |
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Format: | artículo biblioteca |
Language: | English |
Published: |
Elsevier
2016
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Subjects: | Niemann-Pick disease, Storage diseases, Sphingolipids, Brain lipids, Lipids, Flavivirus, |
Online Access: | http://hdl.handle.net/20.500.12792/2671 http://hdl.handle.net/10261/293105 |
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