Herpes simplex virus type 1-induced transcriptional networks of corneal endothelial cells indicate antigen presentation function.

PURPOSE

To determine the transcriptional response of cultured human corneal endothelial (HCEn) cells after herpes simplex virus type (HSV-1) infection and to characterize the primary functional elements and antiviral responses.

METHODS

Immortalized HCEn cells were infected with HSV-1, and the global transcriptional profile was determined. The transcriptional networks of HCEn cells were constructed, and the inflammatory network nodes were evaluated for induction of candidate inflammatory mediators by protein array analyses. HSV-1-specific allogeneic T cells isolated from HSV-1-infected donors were co-cultured with HSV-1-pulsed HCEn cells, and T cell activation was assessed for antigen-specific proliferation.

RESULTS

HSV-1 infection induced a global transcriptional activation with 331 genes significantly up- or downregulated compared with mock-infected HCEn cells (P < 0.01; 4< or 0.25> threshold). Network analysis showed that the HSV-1-induced transcriptome was specifically associated with antigen presentation, interferon-related responses, and cellular development, and was characterized by NF-κB and extracellular signal-regulated kinase signaling pathways. The primary associated function in the transcriptome was antigen presentation. Protein array analysis identified significant elevation of genes related to antigen presentation: IL-6, IP-10, HVEML, and interferon-γ. In addition, inflammatory cytokines including IL-8, MCP-1, TIMP-1, RANTES, I-309, MIF, MCP-2, IL-10, and SDF-1, in descending order, were significantly elevated. Mixed lymphocyte reaction assays showed that HSV-1-pulsed HCEn cells stimulated antigen-specific proliferation of allogeneic T lymphocytes.

CONCLUSIONS

HCEn cells respond to HSV-1 infection by initiating antigen presentation-related inflammatory responses, and they may serve as antigen-presenting cells.