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

TitleInfection-Induced Peroxisome Biogenesis Is a Metabolic Strategy for Herpesvirus Replication.
Publication TypeJournal Article
Year of Publication2018
AuthorsBeltran, PMJean, Cook, KC, Hashimoto, Y, Galitzine, C, Murray, LA, Vitek, O, Cristea, IM
JournalCell Host Microbe
Date Published2018 Oct 10
KeywordsAdenoviridae, Adenoviridae Infections, Cell Line, Cytomegalovirus, Cytomegalovirus Infections, Fibroblasts, Herpes Simplex, Herpesvirus 1, Human, Humans, Organelle Biogenesis, Peroxisomes, Primary Cell Culture, Proteomics, Virus Replication

<p>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.</p>

Alternate JournalCell Host Microbe
PubMed ID30269970
PubMed Central IDPMC6195127
Grant ListR01 GM114141 / GM / NIGMS NIH HHS / United States