Objective:

The aim of this research is to determine the effect of MST-312 on HSV-1 infection in neuronal cells.

Background:

Herpes simplex viruses (HSV) cause disease ranging from cold sores to life-threatening brain infections. HSV typically enters the body through mucosal epithelium, where its initial replication takes place. During this time, HSV enters sensory neurons servicing the site of infection. Most of the infected neurons eventually enter a latent state. However, in cases of HSV encephalitis in neonates, the virus spreads to the central nervous system and undergoes lytic replication without entering latency. Approximately 23% of the most severe neonatal HSV infections are fatal, even with current antiviral treatment. Thus, identifying additional antivirals that could block or reduce HSV replication in neurons would greatly reduce the disease burden of this virus. We previously determined that a cell permeable, reversible inhibitor of the telomerase enzyme, MST-312, suppresses HSV infection in epithelial cells. 

Design/Methods:

Lund human mesencephalic (LUHMES) cells, which are human embryonic neuronal precursor cells that can be differentiated into post-mitotic neuronal cells, were used as the model for neuronal infection. LUHMES cells were differentiated for 5 days prior to experiments. Synaptophysin and βIII-tubulin were used as markers of neuronal differentiation. Cytotoxicity of MST-312 on LUHMES cells was assessed via MTT assay.  Differentiated LUHMES cells were infected with HSV-1 in the presence or absence of 20 – 100 µM MST-312.  Virus isolated from cultures were quantified via plaque assays.   

Results:

Immunoblots of LUHMES cells for neuronal markers confirmed differentiation. MST-312 concentrations tested did not lead to increased cell toxicity compared to controls.  MST-312 treatment significantly reduced the production of HSV-1.   

Conclusions:

Our data shows that MST-312 can inhibit the replication of HSV-1 in neuronal cells. These data support further investigation into MST-312’s antiviral properties, which may provide novel targets for HSV therapies.