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

ABSTRACT Sex 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 infl...

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Autores principales:	Rachel E. Riccio, Seo J. Park, Richard Longnecker, Sarah J. Kopp
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	herpes simplex virus herpes stromal keratitis ocular sex differences Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b62e06f1255f428b85047d7a11ebd6d0
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spelling	oai:doaj.org-article:b62e06f1255f428b85047d7a11ebd6d02021-11-15T15:22:22ZCharacterization of Sex Differences in Ocular Herpes Simplex Virus 1 Infection and Herpes Stromal Keratitis Pathogenesis of Wild-Type and Herpesvirus Entry Mediator Knockout Mice10.1128/mSphere.00073-192379-5042https://doaj.org/article/b62e06f1255f428b85047d7a11ebd6d02019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00073-19https://doaj.org/toc/2379-5042ABSTRACT Sex 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. IMPORTANCE Sex 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.Rachel E. RiccioSeo J. ParkRichard LongneckerSarah J. KoppAmerican Society for Microbiologyarticleherpes simplex virusherpes stromal keratitisocularsex differencesMicrobiologyQR1-502ENmSphere, Vol 4, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	herpes simplex virus herpes stromal keratitis ocular sex differences Microbiology QR1-502
spellingShingle	herpes simplex virus herpes stromal keratitis ocular sex differences Microbiology QR1-502 Rachel E. Riccio Seo J. Park Richard Longnecker Sarah J. Kopp 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
description	ABSTRACT Sex 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. IMPORTANCE Sex 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.
format	article
author	Rachel E. Riccio Seo J. Park Richard Longnecker Sarah J. Kopp
author_facet	Rachel E. Riccio Seo J. Park Richard Longnecker Sarah J. Kopp
author_sort	Rachel E. Riccio
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/b62e06f1255f428b85047d7a11ebd6d0
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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

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