PDF(Pubmed)
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.
摘要：
维甲酸(RA),来源于视黄醇（ROL），是细胞生长不可或缺的一部分，分化,和器官发生。已知RA可以抑制单纯疱疹病毒(HSV)的复制,但是甲疱疹病毒与RA代谢之间的相互作用尚不清楚。我们目前的研究表明，甲疱疹病毒（HSV-1和伪狂犬病病毒，PRV）感染通过激活P53抑制了ROL的RA合成，P53增加了视黄醇还原酶3（DHRS3）的表达，该酶可将视黄醛转化回ROL。这个过程依赖于病毒触发的DNA损伤反应,I类组蛋白脱乙酰酶的降解，以及随后组蛋白H3和H4的高乙酰化。对抗DHRS3或P53能够实现更高的RA合成并减少病毒生长。RA通过促进ABCA1-和ABCG1介导的脂质流出来增强抗病毒防御。用视黄酸受体（RAR）激动剂palovarotene治疗可保护小鼠免受HSV-1感染，从而提供了一个潜在的治疗策略来对抗病毒感染。
