ZDHHC14 and APT2 regulate the palmitoylation of HSV-2 gB

IF 2.4 3区医学 Q3 VIROLOGY

Virology Pub Date : 2025-06-25 DOI:10.1016/j.virol.2025.110614

Yajie Chen , Guangfu Yu , Shan Gao , Leiliang Zhang

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引用次数: 0

Abstract

Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted pathogen known for causing genital herpes. Glycoprotein B (gB) of HSV-2 plays a crucial role in viral entry and infection. However, its post-translational modifications are not well understood. This study investigated the palmitoylation of HSV-2 gB, identifying cysteine residue 8 (C8) as a critical palmitoylation site. Using an acyl-biotin exchange assay, we confirmed that gB was indeed palmitoylated, and treatment with 2-bromopalmitate significantly reduced this modification. Further analysis revealed that ZDHHC14 interacted with gB and facilitated its palmitoylation. We also identified APT2 as a negative regulator of gB palmitoylation. Importantly, palmitoylation enhanced gB's localization to the plasma membrane, whereas the C8S mutation substantially impaired this localization. Functionally, palmitoylation of gB enhanced the infective efficiency of HSV-2 pseudotyped particles (pp) and live viruses, while both palmitoyltransferase and APT2 inhibition affected the entry efficiency of HSV-2pp. Our findings demonstrate that the palmitoylation of gB is crucial for its localization to the membrane and for facilitating efficient HSV-2 infection, highlighting palmitoylation as a promising target for antiviral interventions and providing new insights into the pathogenesis of HSV-2.

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ZDHHC14和APT2调控HSV-2 gB的棕榈酰化

单纯疱疹病毒2型（HSV-2）是一种常见的性传播病原体，已知可引起生殖器疱疹。2型单纯疱疹病毒的糖蛋白B （gB）在病毒进入和感染中起着至关重要的作用。然而，其翻译后修饰尚不清楚。本研究对HSV-2 gB的棕榈酰化进行了研究，发现半胱氨酸残基8 （C8）是一个关键的棕榈酰化位点。通过酰基生物素交换实验，我们证实了gB确实是棕榈酰化的，用2-溴棕榈酰酸盐处理可以显著减少这种修饰。进一步分析发现ZDHHC14与gB相互作用并促进其棕榈酰化。我们还发现APT2是gB棕榈酰化的负调节因子。重要的是，棕榈酰化增强了gB在质膜上的定位，而C8S突变则严重损害了这种定位。功能上，gB棕榈酰化可提高HSV-2假型颗粒（pp）和活病毒的感染效率，而棕榈酰转移酶和APT2抑制均影响HSV-2pp的进入效率。我们的研究结果表明，gB的棕榈酰化对于其在膜上的定位和促进HSV-2的有效感染至关重要，突出了棕榈酰化作为抗病毒干预的有希望的靶点，并为HSV-2的发病机制提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Virology 医学-病毒学

CiteScore

6.00

自引率

0.00%

发文量

157

审稿时长

50 days

期刊介绍： Launched in 1955, Virology is a broad and inclusive journal that welcomes submissions on all aspects of virology including plant, animal, microbial and human viruses. The journal publishes basic research as well as pre-clinical and clinical studies of vaccines, anti-viral drugs and their development, anti-viral therapies, and computational studies of virus infections. Any submission that is of broad interest to the community of virologists/vaccinologists and reporting scientifically accurate and valuable research will be considered for publication, including negative findings and multidisciplinary work.Virology is open to reviews, research manuscripts, short communication, registered reports as well as follow-up manuscripts.