Journal
VIROLOGY
Volume 516, Issue -, Pages 147-157Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2018.01.009
Keywords
Flavivirus; Capsid; Akt-signalling; Apoptosis; Protein phosphatase-1; Dengue virus
Categories
Funding
- Frederick Banting & Charles Best Canada Graduate Doctoral Scholarship from Canadian Institutes of Health Research (CIHR)
- CIHR [MOP-125903, PJT-148699, ZV1-149782]
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Flaviviruses depend on multiple host pathways during their life cycles and have evolved strategies to avoid the innate immune response. Previously, we showed that the West Nile virus capsid protein plays a role in this process by blocking apoptosis. In this study, we examined how expression of capsid proteins from several flaviviruses affects apoptosis and other host processes that impact virus replication. All of the tested capsid proteins protected cells from Fas-dependent apoptosis through a mechanism that requires activated Akt. Capsid expression upregulated other Akt-dependent cellular processes including expression of glucose transporter 1 and mitochondrial metabolism. Protein phosphatase 1, which is known to inactivate Akt, was identified as a DENV capsid interacting protein. This suggests that DENV capsid expression activates Akt by sequestering phosphatases that downregulate phospho-Akt. Capsid-dependent upregulation of Akt would enhance downstream signalling pathways that affect cell survival and metabolism, thus providing a favourable environment for virus replication.
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