RNA seq analysis of chemokine expression in HSV-1 infected human iris stromal cells 2576

Abstract Description Herpes simplex virus 1 (HSV-1) associated uveitis is a common cause of anterior uveitis. Here, we use human iris stromal (HIS) cells to demonstrate HSV-1 infection-mediated stromal cell chemokine production. We hypothesize that HIS cells are an important source of chemokines following HSV-1 infection and contribute to the onset of anterior uveitis. Primary cultures of HIS cells were infected with HSV-1 at different time points, followed by RNA seq analysis. HIS cell supernatants were also generated after HSV-1 infection to determine chemokine protein levels using an antibody array. Finally, HIS cells were stimulated with TNFa and IFNg to mimic the inflammatory environment and chemokine levels were determined. The study showed that HSV-1 infected HIS cells had an increase in CCL2 transcription for up to 6 hours post infection which agreed with the CCL2 protein secretion studies at 48 hours post HSV-1 infection and post cytokine stimulation. Additionally, HIS cell CXCL1 transcription was significantly elevated at 1 and 3 hours post HSV-1 infection, which agreed with CXCL1 secretion from cytokine stimulated HIS cells at 24 hours. The expression of other chemokines, CXCL2 and CXCL3, did not significantly change with HSV-1 infection. In conclusion, HSV-1 infection of HIS cells stimulates the transcription and secretion of leukocyte chemoattractants, CCL2 and CXCL1, suggesting an important role for these chemokines in the pathogenesis of HSV-1 associated anterior uveitis. Funding Sources Midwestern University intramural research funds Topic Categories Viral Immunology (VIR)