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

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2018 Oct 2

PMID 30269970

Citations 46

Authors

Pierre M Jean Beltran

Katelyn C Cook

Yutaka Hashimoto

Cyril Galitzine

Laura A Murray

Olga Vitek

Ileana M Cristea

Affiliations

Soon will be listed here.

Abstract

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 to peroxisomes to support their replication. Targeted proteomic quantification revealed a global virus-induced upregulation of peroxisomal proteins. Mathematical modeling and microscopy structural analysis show that infection triggers peroxisome growth and fission, leading to increased peroxisome numbers and irregular disc-like structures. HCMV-induced peroxisome biogenesis increased the phospholipid plasmalogen, thereby enhancing virus production. Peroxisome regulation and dependence were not observed for the non-enveloped adenovirus. Our findings uncover a role of peroxisomes in viral pathogenesis, with likely implications for multiple enveloped viruses.

Citing Articles

PEX1 remains functional in peroxisome biogenesis but is rapidly degraded by the proteasome.

Sheedy C, Chowdhury S, Ali B, Miyamoto J, Pang E, Bacal J bioRxiv. 2024; .

PMID: 39713301 PMC: 11661142. DOI: 10.1101/2024.12.10.627778.

Salmonella Typhimurium effector SseI regulates host peroxisomal dynamics to acquire lysosomal cholesterol.

Raj D, Nair A, Singh A, Basu S, Sarkar K, Sharma J EMBO Rep. 2024; 26(3):656-689.

PMID: 39695325 PMC: 11811301. DOI: 10.1038/s44319-024-00328-x.

HCMV strain- and cell type-specific alterations in membrane contact sites point to the convergent regulation of organelle remodeling.

Hofstadter W, Park J, Lum K, Chen S, Cristea I J Virol. 2024; 98(11):e0109924.

PMID: 39480111 PMC: 11575408. DOI: 10.1128/jvi.01099-24.

Acanthamoeba polyphaga de novo transcriptome and its dynamics during Mimivirus infection.

Bickels Nuri R, Feldmesser E, Fridmann-Sirkis Y, Keren-Shaul H, Nevo R, Minsky A Sci Rep. 2024; 14(1):25894.

PMID: 39472705 PMC: 11522460. DOI: 10.1038/s41598-024-76078-6.

Role and Function of Peroxisomes in Neuroinflammation.

Sarkar C, Lipinski M Cells. 2024; 13(19.

PMID: 39404418 PMC: 11476013. DOI: 10.3390/cells13191655.

References

Zhu H, Shen Y, Shenk T . Human cytomegalovirus IE1 and IE2 proteins block apoptosis. J Virol. 1995; 69(12):7960-70. PMC: 189741. DOI: 10.1128/JVI.69.12.7960-7970.1995. View

Lee M, Sumpter Jr R, Zou Z, Sirasanagandla S, Wei Y, Mishra P . Peroxisomal protein PEX13 functions in selective autophagy. EMBO Rep. 2016; 18(1):48-60. PMC: 5210156. DOI: 10.15252/embr.201642443. View

Ivanova P, Milne S, Byrne M, Xiang Y, Brown H . Glycerophospholipid identification and quantitation by electrospray ionization mass spectrometry. Methods Enzymol. 2007; 432:21-57. DOI: 10.1016/S0076-6879(07)32002-8. View

Lohner K, Balgavy P, Hermetter A, Paltauf F, Laggner P . Stabilization of non-bilayer structures by the etherlipid ethanolamine plasmalogen. Biochim Biophys Acta. 1991; 1061(2):132-40. DOI: 10.1016/0005-2736(91)90277-f. View

Zemski Berry K, Murphy R . Electrospray ionization tandem mass spectrometry of glycerophosphoethanolamine plasmalogen phospholipids. J Am Soc Mass Spectrom. 2004; 15(10):1499-508. DOI: 10.1016/j.jasms.2004.07.009. View

MacLean B, Tomazela D, Shulman N, Chambers M, Finney G, Frewen B . Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics. 2010; 26(7):966-8. PMC: 2844992. DOI: 10.1093/bioinformatics/btq054. View

Schrader M, Fahimi H . Peroxisomes and oxidative stress. Biochim Biophys Acta. 2006; 1763(12):1755-66. DOI: 10.1016/j.bbamcr.2006.09.006. View

Liu S, Sharon-Friling R, Ivanova P, Milne S, Myers D, Rabinowitz J . Synaptic vesicle-like lipidome of human cytomegalovirus virions reveals a role for SNARE machinery in virion egress. Proc Natl Acad Sci U S A. 2011; 108(31):12869-74. PMC: 3150939. DOI: 10.1073/pnas.1109796108. View

Hua R, Kim P . Multiple paths to peroxisomes: Mechanism of peroxisome maintenance in mammals. Biochim Biophys Acta. 2015; 1863(5):881-91. DOI: 10.1016/j.bbamcr.2015.09.026. View

10.

Kemp S, Wei H, Lu J, Braiterman L, McGuinness M, Moser A . Gene redundancy and pharmacological gene therapy: implications for X-linked adrenoleukodystrophy. Nat Med. 1998; 4(11):1261-8. DOI: 10.1038/3242. View

11.

Collins C, Gould S . Identification of a common PEX1 mutation in Zellweger syndrome. Hum Mutat. 1999; 14(1):45-53. DOI: 10.1002/(SICI)1098-1004(1999)14:1<45::AID-HUMU6>3.0.CO;2-J. View

12.

Braverman N, Moser A . Functions of plasmalogen lipids in health and disease. Biochim Biophys Acta. 2012; 1822(9):1442-52. DOI: 10.1016/j.bbadis.2012.05.008. View

13.

Muntau A, Mayerhofer P, Paton B, Kammerer S, Roscher A . Defective peroxisome membrane synthesis due to mutations in human PEX3 causes Zellweger syndrome, complementation group G. Am J Hum Genet. 2000; 67(4):967-75. PMC: 1287898. DOI: 10.1086/303071. View

14.

Li X, Baumgart E, Morrell J, Jimenez-Sanchez G, Valle D, Gould S . PEX11 beta deficiency is lethal and impairs neuronal migration but does not abrogate peroxisome function. Mol Cell Biol. 2002; 22(12):4358-65. PMC: 133847. DOI: 10.1128/MCB.22.12.4358-4365.2002. View

15.

Di Cara F, Sheshachalam A, Braverman N, Rachubinski R, Simmonds A . Peroxisome-Mediated Metabolism Is Required for Immune Response to Microbial Infection. Immunity. 2017; 47(1):93-106.e7. DOI: 10.1016/j.immuni.2017.06.016. View

16.

Deutsch E, Csordas A, Sun Z, Jarnuczak A, Perez-Riverol Y, Ternent T . The ProteomeXchange consortium in 2017: supporting the cultural change in proteomics public data deposition. Nucleic Acids Res. 2016; 45(D1):D1100-D1106. PMC: 5210636. DOI: 10.1093/nar/gkw936. View

17.

Steinberg S, Dodt G, Raymond G, Braverman N, Moser A, Moser H . Peroxisome biogenesis disorders. Biochim Biophys Acta. 2006; 1763(12):1733-48. DOI: 10.1016/j.bbamcr.2006.09.010. View

18.

Wessel D, Flugge U . A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids. Anal Biochem. 1984; 138(1):141-3. DOI: 10.1016/0003-2697(84)90782-6. View

19.

Wanders R, Waterham H . Biochemistry of mammalian peroxisomes revisited. Annu Rev Biochem. 2006; 75:295-332. DOI: 10.1146/annurev.biochem.74.082803.133329. View

20.

Chahal J, Flint S . Timely synthesis of the adenovirus type 5 E1B 55-kilodalton protein is required for efficient genome replication in normal human cells. J Virol. 2012; 86(6):3064-72. PMC: 3302336. DOI: 10.1128/JVI.06764-11. View