AN UNSUAL VIRAL ENDOTHELIITIS

HSV infection can affect nearly every ocular tissue. In cases of corneal involvement, the epithelium, stroma, or endothelium may be affected. Both herpes stromal keratitis (HSK) and HSV endotheliitis can present clinically with stromal opacity and, therefore, may be difficult to distinguish. In this case we will be describing a viral endotheliitis with a particular aspect on the corneal endothelium.

OPTN limits herpes stromal keratitis severity and demyelination through negative regulation of IL-17 and hyperinflammatory T-cell response

Herpes stromal keratitis (HSK) is a result of the inflammatory sequelae following primary and recurrent Herpes simplex virus type-1 (HSV-1) infections. This pathology is known to be mediated by immunopathogenic T cell responses against viral antigens, however most individuals infected with HSV-1 never exhibit signs of this immunopathology. Recent studies have identified the host restriction factor, optineurin (OPTN), as an inhibitor of viral spread in the central nervous system, protecting hosts from viral encephalopathy. In an HSV-1 corneal infection mouse model on OPTN knockout mice, we assess the contribution of OPTN to ameliorating the clinical manifestations of HSK. We identify that OPTN protects the host from loss of ocular and whisker sensitivity and opacification of the cornea. scRNA-seq of the trigeminal ganglion (TG) reveals that transcription changes to the peripheral neurons and immune cell populations drive the expression of Il-17A in CD4 and CD8 T cells, as well as increased infiltration of T cells into the TG. This leads to demyelination and the observed HSK pathology.

Characterization of Sex Differences in Ocular Herpes Simplex Virus 1 Infection and Herpes Stromal Keratitis Pathogenesis of Wild-Type and Herpesvirus Entry Mediator Knockout Mice

ABSTRACTSex differences related to immune response and inflammation play a role in the susceptibility and pathogenesis of a variety of viral infections and disease (S. L. Klein, Bioessays 34:1050–1059, 2012,https://doi.org/10.1002/bies.201200099). Herpes simplex virus 1 (HSV-1) causes chronic inflammatory disease in the cornea, an immune-privileged tissue, resulting in irreversible damage and blindness in affected individuals (A. Rowe, A. St Leger, S. Jeon, D. K. Dhaliwal, et al., Prog Retin Eye Res 32:88–101, 2013,https://doi.org/10.1016/j.preteyeres.2012.08.002). Our research focuses on the role of herpesvirus entry mediator (HVEM) as an immune regulator during ocular HSV-1 infection. Mice lacking HVEM (HVEM knockout [KO] mice) exhibit lower levels of immune cell infiltrates and less severe ocular disease in the cornea than wild-type (WT) mice. As sex differences contribute to pathogenesis in many inflammatory diseases, we tested whether sex acts as a biological variable in the immune response to HSV-1 infection and herpes stromal keratitis (HSK) pathogenesis. Adult male and female WT and HVEM KO mice were inoculated with HSV-1 via corneal scarification and monitored daily for disease course. Viral titers were determined, and immune cell infiltrates were collected and analyzed. Our results indicated no significant differences in viral titers in tear film or affected tissues, in immune cell infiltration, or in clinical symptoms between males and females of either genotype. These results suggest that sex is not a significant biological variable in this experimental model and that male and female mice of the C57BL/6 background can be used similarly in studies of ocular HSV-1 pathogenesis.IMPORTANCESex hormones have come to be considered an important factor for the development of certain diseases only recently and as such should continue to be considered a biological variable. Ocular HSV-1, and the resulting HSK, is the leading cause of infectious blindness worldwide. We compared levels of ocular HSV-1 infection and pathogenesis in the two sexes and found no significance differences between male and female WT mice or HVEM KO mice.

Characterization of Sex Differences in Ocular HSV-1 Infection and Herpes Stromal Keratitis Pathogenesis of Wild Type and Herpesvirus Entry Mediator Knockout Mice

ABSTRACTSex differences related to immune response and inflammation play a role in the susceptibility and pathogenesis of a variety of viral infections and disease (S. L. Klein, Bioessays 34:1050-9, 2012). Herpes simplex virus type 1 (HSV-1) causes chronic inflammatory disease in the cornea, an immune privileged tissue, resulting in irreversible damage and blindness in affected individuals (A. Rowe, A. St Leger, S. Jeon, D. K. Dhaliwal, J. E. Knickelbein, and E. Vilain, Prog Retin Eye Res 32:88-101, 2013). Our research focuses on the role of Herpes Viral Entry Mediator (HVEM) as an immune regulator during ocular HSV-1 infection. Mice lacking HVEM (HVEM KO) exhibit lower immune cell infiltrates and less severe ocular disease in the cornea compared to wild type (WT) mice. As sex differences contribute to pathogenesis in many inflammatory diseases, we tested sex as a biological variable in the immune response to HSV-1 infection and Herpes Stromal Keratitis pathogenesis (HSK). Adult male and female WT and HVEM KO mice were inoculated with HSV-1 via corneal scarification and monitored daily for disease course. Viral titers and immune cell infiltrates were collected and analyzed. Our results indicate no significant difference in viral titers in tear film or affected tissues; immune cell infiltration; or clinical symptoms between males and females of either genotype. These results suggest that sex is not a significant biological variable in this experimental model, and that male and female mice can similarly be used in studies of ocular HSV-1 pathogenesis.IMPORTANCESex hormones have only recently been considered as an important factor for the development of certain diseases and as such should continue to be considered as a biological variable. Ocular Herpesvirus Type 1 (HSV-1), and the resulting Herpes Stromal Keratitis, is the leading cause of infectious blindness worldwide. We compared ocular HSV-1 infection and pathogenesis between sexes and found no significance difference between male and female wild type mice or herpesvirus entry mediator knockout mice. Therefore, male and female mice can be used interchangeably in studying ocular HSV-1 pathogenesis.