UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Alphavirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic changes

Mazzon, M; Castro, C; Thaa, B; Liu, L; Mutso, M; Liu, X; Mahalingam, S; ... McInerney, GM; + view all (2018) Alphavirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic changes. PLoS Pathog , 14 (1) , Article e1006835. 10.1371/journal.ppat.1006835. Green open access

[img]
Preview
Text
journal.ppat.1006835.pdf - Published version

Download (9MB) | Preview

Abstract

Virus reprogramming of cellular metabolism is recognised as a critical determinant for viral growth. While most viruses appear to activate central energy metabolism, different viruses have been shown to rely on alternative mechanisms of metabolic activation. Whether related viruses exploit conserved mechanisms and induce similar metabolic changes is currently unclear. In this work we investigate how two alphaviruses, Semliki Forest virus and Ross River virus, reprogram host metabolism and define the molecular mechanisms responsible. We demonstrate that in both cases the presence of a YXXM motif in the viral protein nsP3 is necessary for binding to the PI3K regulatory subunit p85 and for activating AKT. This leads to an increase in glucose metabolism towards the synthesis of fatty acids, although additional mechanisms of metabolic activation appear to be involved in Ross River virus infection. Importantly, a Ross River virus mutant that fails to activate AKT has an attenuated phenotype in vivo, suggesting that viral activation of PI3K/AKT contributes to virulence and disease.

Type: Article
Title: Alphavirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic changes
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.ppat.1006835
Publisher version: http://doi.org/10.1371/journal.ppat.1006835
Language: English
Additional information: Copyright: © 2018 Mazzon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10043155
Downloads since deposit
53Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item