Unknown

Dataset Information

0

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


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.

SUBMITTER: Mazzon M 

PROVIDER: S-EPMC5805360 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Mazzon Michela M   Castro Cecilia C   Thaa Bastian B   Liu Lifeng L   Mutso Margit M   Liu Xiang X   Mahalingam Suresh S   Griffin Julian L JL   Marsh Mark M   McInerney Gerald M GM  

PLoS pathogens 20180129 1


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  ...[more]

Similar Datasets

| S-EPMC8192787 | biostudies-literature
| S-EPMC8034842 | biostudies-literature
| S-EPMC6041272 | biostudies-literature
| S-EPMC2556239 | biostudies-literature
| S-EPMC5122961 | biostudies-literature
| S-EPMC8113585 | biostudies-literature
| S-EPMC10918153 | biostudies-literature
| S-EPMC7294049 | biostudies-literature
| S-EPMC8655334 | biostudies-literature
| S-EPMC5260505 | biostudies-literature