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Updated: Jul 20, 2026

A Primary Neuron Culture System for the Study of Herpes Simplex Virus Latency and Reactivation
Published on: April 2, 2012
A novel, cell-specific attenuation of a herpes simplex virus type 1 infection in vivo
T E Kienzle1, T M Chen, R E Mrak
1Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. tkienz@arlpc.org
Abstract:
We have observed a cell-specific attenuation of herpes simplex virus type 1 strain 17syn+ in vivo that was dependent upon the cell type used to grow the virus. Direct corneal infection of rabbits with 17syn+ propagated in Vero cells caused 60% (6 of 10) to develop severe central nervous system (CNS) disease as evidenced by seizures and/or paralysis; all neurologically impaired rabbits died. In contrast, infection of rabbits with 17syn+ propagated in BHK-21 cells induced seizures and was fatal in 10% (1 of 10). The cell-specific attenuation of a 17syn+ occurred after one growth cycle in BHK-21 cells. To determine whether the decreased virulence of the BHK-21 cell-grown virus correlated with a less severe CNS inflammatory reaction, CNS tissues from rabbits infected with 17syn+ grown in Vero and BHK-21 cells were compared. Histopathological analyses revealed no differences in the location or severity of inflammatory lesions from rabbits infected with virus grown in either cell type. Virus-induced corneal disease was less dependent upon the cell type used to propagate the virus as there were no significant differences in the type or severity of observed corneal lesions. Possible explanations based on differences between Vero and BHK-21 cells are discussed.
Insights
Herpes simplex virus type 1 (HSV-1) virulence in rabbits depends on the cell type used for virus propagation. Growing HSV-1 in BHK-21 cells, not Vero cells, significantly reduced severe central nervous system (CNS) disease and mortality.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Herpes simplex virus type 1 (HSV-1) is a significant human pathogen.
- HSV-1 can cause severe central nervous system (CNS) disease, including encephalitis and meningitis.
- The in vivo behavior of viruses can be influenced by their in vitro propagation methods.
Purpose of the Study:
- To investigate the impact of cell type used for HSV-1 propagation on viral virulence and disease severity in a rabbit model.
- To determine if cell-specific attenuation of HSV-1 affects the inflammatory response in the CNS.
- To compare the effects of HSV-1 grown in different cell lines on corneal disease.
Main Methods:
- Herpes simplex virus type 1 strain 17syn+ was propagated in either Vero or BHK-21 cells.
- Rabbits were infected via direct corneal inoculation.
- Disease severity, neurological signs (seizures, paralysis), mortality, and histopathological CNS and corneal lesions were assessed.
Main Results:
- HSV-1 propagated in Vero cells caused severe CNS disease and death in 60% of rabbits.
- HSV-1 propagated in BHK-21 cells induced seizures but resulted in fatality in only 10% of rabbits.
- No significant differences were observed in the location or severity of CNS inflammatory lesions or corneal disease between the two virus propagation groups.
Conclusions:
- Cell type used for HSV-1 propagation significantly influences in vivo neurovirulence.
- HSV-1 attenuation in BHK-21 cells does not correlate with reduced CNS inflammation.
- Corneal disease severity is less dependent on the cell type used for HSV-1 propagation.
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