Viral infection of human neurons triggers strain-specific differences in host neuronal and viral transcriptomes

Infection with herpes simplex virus 1 (HSV-1) occurs in over half the global population, causing recurrent orofacial and/or genital lesions. Individual strains of HSV-1 demonstrate differences in neurovirulence in vivo, suggesting that viral genetic differences may impact strain phenotype. In the present study, differentiated SH-SY5Y human neuronal cells were infected with one of three HSV-1 strains known to differ in neurovirulence in vivo. Host and viral RNA were sequenced simultaneously, revealing strain-specific differences in viral and host transcription in infected neurons. Neuronal morphology and protein localization data revealed that HSV-1 induces strain-specific differences in neuronal structure and adherens junctions. Comparison of viral protein expression in neurons and epithelial cells demonstrated that a number of differences were neuron-specific, suggesting that strain-to-strain variations in host and virus transcription are cell type-dependent. Together, these data demonstrate the importance of studying virus strain- and cell-type-specific factors that may contribute to neurovirulence and highlight the specificity of HSV-1-host interactions.