The impact of fatty acid synthase on HSV-1 infection dynamics

  • PLoS Pathog. 2025 May 6;21(5):e1013068. doi: 10.1371/journal.ppat.1013068.
Camilla Albano  1 ,  Linda Trifirò  1 ,  Weronika Hewelt-Belka  2 ,  Dana M Cairns  3 ,  Selina Pasquero  1 ,  Gloria Griffante  1 ,  Francesca Gugliesi  1 ,  Greta Bajetto  1  4 ,  Dorota Garwolińska  2 ,  Marika Rossi  5 ,  Marta Vallino  5 ,  Mario Malerba  6 ,  Marco De Andrea  1  4 ,  David L Kaplan  3 ,  Valentina Dell'Oste  1 ,  Matteo Biolatti  1
Affiliations
  • 1. Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy.
  • 2. Department of Analytical Chemistry, Gdańsk University of Technology, Gdańsk, Poland.
  • 3. Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, United States of America.
  • 4. CAAD Center for Translational Research on Autoimmune and Allergic Disease, University of Piemonte Orientale, Novara, Italy.
  • 5. Institute for Sustainable Plant Protection, National Research Council of Italy, Turin, Italy.
  • 6. INRIM Istituto Nazionale di Ricerca Metrologica, Turin, Italy.
PMID: 40327680 DOI: 10.1371/journal.ppat.1013068
Abstract

Herpes simplex virus type-1 (HSV-1) is a widespread human pathogen that relies on host cell pathways, including those involved in metabolism to support replication. Here, we demonstrate that de novo lipogenesis is essential for HSV-1 infectivity. Specifically, HSV-1 Infection upregulates fatty acid synthase (FASN) expression, accompanied by a marked increase in lipids and a differential lipid species distribution. Conversely, silencing FASN or applying FASN inhibitors (i.e., CMS121 and C75) markedly reduces the infectivity of newly released HSV-1 virions, suggesting that, while initial replication remains unaffected, FASN is crucial for maintaining virion structure and facilitating entry into host cells. Additionally, we show that a source of lipid-rich external factors provided by fetal bovine serum significantly increases HSV-1 infectivity. Specifically, HSV-1 Infection enhanced CD36-mediated fatty acid uptake, especially in FASN-depleted cells, compensating for reduced lipogenesis. Blocking CD36 function with SSO further decreased viral infectivity, demonstrating the critical role of lipid uptake in HSV-1 life cycle. Altogether, our findings reveal how HSV-1 manipulates lipid metabolism, offering insights into its association with chronic disease and therapeutic intervention.

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