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

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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Publication Details

Journal
PLoS Pathogens
Published
2025-05-06
DOI
https://doi.org/10.1371/journal.ppat.1013068
Citations
2
Primary Topic
Herpesvirus Infections and Treatments
Type
article
Field-Weighted Citation Impact
2.71

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article

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

Gloria Griffante, Marta Vallino, Marco De Andrea, Mario Malerba et al.
2 citations
PLoS Pathogens
Herpesvirus Infections and Treatments
2.71
article

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

Gloria Griffante, Marta Vallino, Marco De Andrea, Mario Malerba, Matteo Biolatti, Selina Pasquero, Francesca Gugliesi, Weronika Hewelt-Belka, Valentina Dell’Oste, David L. Kaplan, Camilla Albano, Dana M. Cairns, Greta Bajetto, Marika Rossi, Dorota Garwolińska, Linda Trifirò
article en
2 citations

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.

PLoS PathogensVol. 21(5)
Tufts University (US), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), Gdańsk University of Technology (PL), Institute for Sustainable Plant Protection (IT), Istituto Nazionale di Ricerca Metrologica (IT), National Research Council (IT), University of Turin (IT)
European Society of Clinical Microbiology and Infectious Diseases, Ministero dell’Istruzione, dell’Università e della Ricerca, Università degli Studi di Torino
Responsible consumption and production
Openalex Percentile: Top 11%
Herpesvirus Infections and Treatments
2.71
DOIOpen Access PDFOpenAlex
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