Weikang Sun,Ke Ren,Jingjing Li,Mengyu Zhang,Qishen Jiang,Lingling Wang,Erguang Li
(199 words) The c-Jun N-terminal kinase (JNK) signaling pathway is required for herpes simplex virus 1 lytic infection and reactivation from latency. JNK signaling regulates cellular processes in response to stress through transcriptional regulation. However, the mechanisms by which JNK regulates HSV-1 infection are less defined. We show here that HSV-1 infection triggers BRD4 transition from chromosome association to transcriptional regulation for viral infection. Specifically, HSV-1 infection induces JNK activation which mediates redistribution of BRD4, an epigenetic reader protein, from chromatin-targeting to association with proteins of transcriptional regulation. BRD4 transitions to viral infection regulation by complexing with P-TEFb, a positive transcription elongation factor, and association with viral DNA. Genetic ablation or perturbation of JNK with chemical inhibitors or siRNA leads to impediment of BRD4 release and inhibition of HSV-1 infection. Both chemotherapeutic agents and irradiation are known to promote JNK activation and HSV reactivation. We show further that JNK agonist or chemotherapeutic agents known to activate JNK have the ability to enhance HSV-1 infection. Our study reveals a novel mechanism by which JNK regulates HSV-1 infection through stress-induced BRD4 function transition from host chromosome association to viral gene expression. The work links recurrent HSV infection by chemotherapeutic agents to JNK activation.
Xu Chen,Jian Yue,Xiongjun Xu,Jiajun Chen,Xuechan Huang,Yukai Huang,Yang Yang,Feng Li,Tianwang Li
Selenium-based nanoparticles exhibit antiviral activity by directly modulating immune function. Despite recent promising developments in utilizing selenium nanoparticles (Se NPs) against viral infections, the impact of surface ligand charge on the conformation and interaction with viral proteins, as well as the effectiveness of Se NPs in anti-Herpes simplex virus 1 (HSV-1) infection remains unexplored. In this study, three types of selenium nanoparticles (CTAB-Se, PVP-Se, SDS-Se) with distinct surface charges were synthesized by modifying the surface ligands. We found that apart from differences in surface charge, the size, morphology, and crystal structure of the three types of Se NPs were similar. Notably, although the lipophilicity and cellular uptake of SDS-Se with a negative charge were lower compared to positively charged CTAB-Se and neutrally charged PVP-Se, SDS-Se exhibited the strongest protein binding force during interaction with HSV-1. Consequently, SDS-Se demonstrated the most potent anti-HSV-1 activity and safeguarded normal cells from damage. The mechanistic investigation further revealed that SDS-Se NPs effectively inhibited the proliferation and assembly of HSV-1 by powerfully suppressing the key genes and proteins of HSV-1 at various stages of viral development. Hence, this study highlights the significant role of surface ligand engineering in the antiviral activity of Se NPs, presenting a viable approach for synthesizing Se NPs with tailored antiviral properties by modulating surface charge. This method holds promise for advancing research on the antiviral capabilities of Se NPs.
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