The combined effects of HSV-1 glycoprotein D and aluminum hydroxide on human neuroblastoma cells: Insights into oxidative DNA damage, apoptosis, and epigenetic modifications

Abstract

Herpes simplex virus type 1 (HSV-1) infections are a significant global health concern due to the virus's ability to evade apoptosis and establish lifelong latency in the peripheral nervous system. The specific viral components responsible for these effects remain unclear, necessitating individual examination of their molecular impacts. This study focused on investigating the effects of recombinant HSV-1 glycoprotein D (HSV-1 gD), a viral protein essential for host cell entry, and/or aluminum hydroxide, a known neurotoxic agent, on reactive oxygen species (ROS) production, apoptotic markers, and epigenetic modifications in SH-SY5Y neuroblastoma cells. Using inhibitory concentration 20 (IC₂₀) values for HSV-1 gD and aluminum hydroxide, experimental groups were established. Intracellular ROS levels, oxidative DNA damage, and the expression and activity of key apoptotic proteins were measured. Additionally, global DNA methylation, histone H3 and H4 acetylation, and the activities of histone deacetylases (HDAC3 and HDAC8) were evaluated. Results of the study showed that both HSV-1 gD and aluminum hydroxide independently increased ROS production and induced apoptosis in SH-SY5Y cells. Notably, significant alterations in epigenetic markers were observed, including decreased global DNA methylation and histone acetylation levels. These epigenetic modifications suggest potential underlying mechanisms for the neurotoxic effects of aluminum hydroxide and HSV-1 gD. In addition to the traditional suggestions for HSV-1 gD as an anti-apoptotic factor, our findings indicate that it may also contribute to neurotoxicity. This study provides new insights into the molecular interactions between viral components and neurotoxic agents and emphasizes the importance of epigenetic regulation in neuronal cell death.

Keywords: Aluminum hydroxide adjuvant; Apoptosis in infection; Epigenetic regulation; Glycoprotein D function in apoptosis; Herpes simplex virus infection.