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Alphaherpesvirus manipulates retinoic acid metabolism for optimal replication.

ABSTRACT: Retinoic acid (RA), derived from retinol (ROL), is integral to cell growth, differentiation, and organogenesis. It is known that RA can inhibit herpes simplex virus (HSV) replication, but the interactions between alphaherpesviruses and RA metabolism are unclear. Our present study revealed that alphaherpesvirus (HSV-1 and Pseudorabies virus, PRV) infections suppressed RA synthesis from ROL by activating P53, which increased retinol reductase 3 (DHRS3) expression-an enzyme that converts retinaldehyde back to ROL. This process depended on the virus-triggered DNA damage response, the degradation of class I histone deacetylases, and the subsequent hyperacetylation of histones H3 and H4. Counteracting DHRS3 or P53 enabled higher RA synthesis and reduced viral growth. RA enhanced antiviral defenses by promoting ABCA1- and ABCG1-mediated lipid efflux. Treatment with the retinoic acid receptor (RAR) agonist palovarotene protected mice from HSV-1 infection, thus providing a potential therapeutic strategy against viral infections.

SUBMITTER: Ming S

PROVIDER: S-EPMC11233922 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Alphaherpesvirus manipulates retinoic acid metabolism for optimal replication.

Ming Shengli S Zhang Shijun S Xing Jiayou J Yang Guoyu G Zeng Lei L Wang Jiang J Chu Beibei B

iScience 20240604 7

Retinoic acid (RA), derived from retinol (ROL), is integral to cell growth, differentiation, and organogenesis. It is known that RA can inhibit herpes simplex virus (HSV) replication, but the interactions between alphaherpesviruses and RA metabolism are unclear. Our present study revealed that alphaherpesvirus (HSV-1 and Pseudorabies virus, PRV) infections suppressed RA synthesis from ROL by activating P53, which increased retinol reductase 3 (DHRS3) expression-an enzyme that converts retinaldeh ...[more]

PMID: 38989466

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Alphaherpesvirus manipulates retinoic acid metabolism for optimal replication.

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Alphaherpesvirus manipulates retinoic acid metabolism for optimal replication.

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