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

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. Jean Beltran et al. reveal the virus-induced modulation of peroxisome functions to facilitate viral replication, a mechanism likely relevant across enveloped viruses. Human cytomegalovirus increases peroxisome numbers and proteome abundance and alters peroxisome shape. This represents a virus strategy to engage peroxisome lipid metabolism for the assembly of infectious particles.