Dataset Information

Infection-Induced Peroxisome Biogenesis Is a Metabolic Strategy for Herpesvirus Replication

ABSTRACT: Peroxisomes are primarily metabolic organelles with important functions in lipid metabolism, such as fatty acid oxidation and ether phospholipid synthesis (e.g. plasmalogens). Certain viruses, such as human cytomegalovirus (HCMV), hijack organelle functions to facilitate their replication and spread. However, the role of peroxisomes in herpesvirus replication remains elusive. Following a discovery that peroxisome proteins are upregulated upon HCMV infection, we quantified the production of plasmalogens, lipids that require peroxisome functions. In agreement with the increase in peroxisome protein abundance, plasmalogen production was increased by HCMV infection.

OTHER RELATED OMICS DATASETS IN: PXD009321

INSTRUMENT(S): Liquid Chromatography MS - Positive (LC-MS (Positive))

PROVIDER: MTBLS652 | MetaboLights | 2018-10-22

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	Infected_02122018_PJ_A.raw	Raw
	Infected_02122018_PJ_B.raw	Raw
	MRCF5_Mock_A_020718_lipid.raw	Raw
	MRCF5_Mock_B_020718_lipid.raw	Raw
	MRCF5_Mock_C_020718_lipid.raw	Raw

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Infection-Induced Peroxisome Biogenesis Is a Metabolic Strategy for Herpesvirus Replication.

Jean Beltran Pierre M PM Cook Katelyn C KC Hashimoto Yutaka Y Galitzine Cyril C Murray Laura A LA Vitek Olga O Cristea Ileana M IM

Cell host & microbe 20180927 4

Viral proteins have evolved to target cellular organelles and usurp their functions for virus replication. Despite the knowledge of these critical functions for several organelles, little is known about peroxisomes during infection. Peroxisomes are primarily metabolic organelles with important functions in lipid metabolism. Here, we discovered that the enveloped viruses human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) induce the biogenesis of and unique morphological changes ...[more]

PMID: 30269970

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Project description:Peroxisome biogenesis diseases (PBDs) are characterized by global defects in peroxisomal function and can result in severe brain, liver, kidney, and bone malfunctions. PBDs are due to mutations in peroxisome biogenesis factors (PEX genes) that are responsible for peroxisome assembly and function. Increasing evidence suggests that peroxisome import functions decline during aging. However, the transcriptome profiling of peroxisome import defects and how they affect disease development are still lacking. PEX5 encodes the cytoplasmic receptors for peroxisome-targeting signal types 1. We generate knock-in human HEK293 cells mutant using CRISPR to transiently express PEX5 cysteine 11 to alanine mutant (PEX5C11A), which blocks PEX5 recycling and exerts dominant negative effect on PEX5 mediated peroxisome import. To identify conserved responses, we perform transcriptomic analysis on Drosophila oenocyte-specific Pex1, Pex12 and Pex5 knockdowns and on human cells with impaired peroxisome import (through expressing PEX5C11A and applying PEX5 siRNA respectively). PEX5C11A induction triggers vast transcriptomic changes, including decreased oxidative phosphorylation, increased MAPK signaling and HIPPO signaling. PEX5 siRNA specifically decreases spliceosome activity and increases cholesterol metabolism. Using gene set enrichment analysis (GSEA), we identify protein processing in endoplasmic reticulum pathway, specifically ER-associated protein degradation (ERAD) pathway is induced in all PEX knockdowns in Drosophila. Peroxisome dysfunction elevates eIF2α phosphorylation in both Drosophila and human cell culture independent of XBP1 activation, suggesting increased integrative stress response (ISR). Moreover, peroxisome stress decreases ribosome biogenesis genes and impairs ribosome biogenesis in flies and human cells. Specifically, peroxisome stress impairs the 5'-ETS cleavage activity during the ribosome biogenesis and dampens 40S small ribosomal export in both flies and human. Our results suggest that reduced ribosome biogenesis and elevated ISR could be conserved cellular response to peroxisome import stress.