Research Article: Transcriptional changes after herpes simplex virus type 1 infection in human trabecular meshwork cells

Date Published: May 28, 2019

Publisher: Public Library of Science

Author(s): Jin A. Choi, Hyun-hee Ju, Ju-Eun Kim, Seon-Kyu Kim, Donghyun Jee, Jiyoung Lee, Chan Kee Park, Soon-young Paik, Nancy M. Sawtell.


Herpes simplex virus type 1 (HSV-1) is causative for hypertensive anterior uveitis. Trabecular meshwork (TM) cells, which are the key cells regulating intraocular pressure (IOP), is considered to be the site of inflammation. We explored the profiles of genes expressed in human TM primary cells upon HSV-1 infection.

Human TM cells were infected with HSV-1 and total RNA was isolated. The global transcriptional gene network analyses were performed in mock-infected and HSV-1 infected TM cells. Using ingenuity pathway analysis, we determined the key biological networks upon HSV-1 infection. The results of microarray analyses were validated using quantitative PCR.

TM cells had a high susceptibility to HSV-1 infection. HSV-1 induced transcriptional suppression of many components related to fibrosis in TM cells. The top biological network related to the genes which were significantly altered upon HSV-1 infection was organismal injury and abnormalities involving TGF-β1 and PDGF-BB. The results of PCR analyses for selected molecules were found to be in good agreement with the microarray data. HSV-1-infected TM cells showed an 80-fold increase in the expression of PDGF-BB, which was further increased by treatment with TGF-β1. HSV-1 also induced a 4-fold increase in the expression of the monocyte chemoattractant protein (MCP)-1, the downstream molecules of PDGF-BB.

In human TM cells, HSV-1 induced transcriptional suppression of many components related to fibrosis and enhanced expression of both PDGF-BB and MCP-1. Our study may provide a novel mechanism for the pathogenesis of HSV-1 infection in TM cells.

Partial Text

Herpes virus is one of the most common etiologies of acute, recurrent, and chronic anterior uveitis worldwide.[1] Herpes simplex virus (HSV) type 1 is ubiquitous and has a characteristic feature of life-long latency following primary infection. It causes various ocular problems such as conjunctivitis, keratitis, and uveitis.

Many growth factors and cytokines are found in the aqueous humor (AH). Among them, sufficient levels of TGF-β exist in the AH for physiologic function of eyes.[11] However, TGF-β generally exerts negative regulatory effect on innate and adaptive immune response. TGF-β signaling is known to result in increased HSV-1 latency.[12] Therefore, human TM cells, nourished by the aqueous humor, should provide an enriched environment for viral replication. Tiwari et al. reported that primary human trabecular meshwork cells were permissive for HSV-1 infection, and TM cell expresses high level of anti-herpesvirus entry mediator, which facilitates viral infection.[13] In accordance with their study, we also found a 2-fold increased expression level of viral gene transcripts in the HSV-1 infected TM cells compared with the Vero cells (Fig 1A), which were exponentially increased at 2 days after infection (Fig 1B).