Inhibition of herpes virus infection in oligodendrocyte cultured cells by valproic acid

• Valproic acid drastically inhibits HSV-1 productivity in HOG infected cells.
• The infection of differentiated oligodendrocytes is more susceptible to the inhibitory effect of valproic acid.
• Viral transcription – especially alpha genes –, replication and also virus egress seem to be affected by valproic acid.

Valproic acid (VPA) is a small fatty acid used for treatment of different neurologic diseases such as epilepsy, migraines or bipolar disorders. VPA modulates different processes of cell metabolism that can lead to alterations in susceptibility of several cell types to the infection of Human Immunodeficiency Virus (HIV), Epstein-Barr virus (EBV), as well as to exert an inhibitory effect on the replication of different enveloped viruses in cultured cells. Taken these data into account and the fact that HSV-1 has been involved in some neuropathies, we have characterized the effect of VPA on this herpesvirus infection of the differentiation/maturation-inducible human oligodendrocyte cell line HOG, which resulted more susceptible to VPA inhibition of virus growth after cell differentiation. In these cells, the role of VPA in virus entry was tackled. Incubation with VPA induced a slight but reproducible inhibition in the virus particles uptake mainly observed when the drug was added in the adsorption or early upon infection. In addition, transcription and expression of viral proteins were significantly downregulated in the presence of VPA. Remarkably, when the infective viral production was assessed, VPA dramatically blocked the detection of infectious HSV-1 particles. Herein, our results indicate that VPA treatment of HOG cells significantly reduces the effect of HSV-1 infection, virus entry and productivity without affecting cellular viability.