Herpes simplex virus-1 KOS-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis

Abstract To investigate the acute clinical, immunological, and corneal nerve changes following corneal HSV-1 KOS-63 strain inoculation. Corneas of C57BL/6 mice were inoculated with either low dose (Ld) or high dose (Hd) HSV-1 KOS-63 or culture medium. Clinical evaluation was conducted up to 7 days p...

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Autores principales:	Hamid-Reza Moein, Victor G. Sendra, Arsia Jamali, Ahmad Kheirkhah, Deshea L. Harris, Pedram Hamrah
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9070c8e29edd4f1ab5b45e8ae1b6d68c
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spelling	oai:doaj.org-article:9070c8e29edd4f1ab5b45e8ae1b6d68c2021-12-02T14:03:57ZHerpes simplex virus-1 KOS-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis10.1038/s41598-021-83412-92045-2322https://doaj.org/article/9070c8e29edd4f1ab5b45e8ae1b6d68c2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83412-9https://doaj.org/toc/2045-2322Abstract To investigate the acute clinical, immunological, and corneal nerve changes following corneal HSV-1 KOS-63 strain inoculation. Corneas of C57BL/6 mice were inoculated with either low dose (Ld) or high dose (Hd) HSV-1 KOS-63 or culture medium. Clinical evaluation was conducted up to 7 days post inoculation (dpi). Viral titers were assessed by standard plaque assay. Excised corneas were stained for CD45 and beta-III tubulin. Corneal flow cytometry was performed to assess changes in leukocyte subpopulations. Corneal sensation was measured using a Cochet-Bonnet esthesiometer. Naïve, sham-infected (post scarification), and McKrae-infected C57BL/6 corneas served as two negative and positive controls, respectively. Compared to Ld infected mice, Hd HSV-1 KOS-63 demonstrated higher incidence of corneal opacity (1.5 ×) and neovascularization (2.6 × ; p < 0.05). At 7 dpi Hd infected mice showed more severe corneal opacity (2.23 vs. 0.87; p = 0.0003), neovascularization (6.00 vs. 0.75; p < 0.0001), and blepharitis (3.11 vs. 2.06; p = 0.001) compared to the Ld group. At 3 dpi epitheliopathy was significantly larger in the Hd group (23.59% vs. 3.44%; p = 0.001). Similarly, corneal opacity was significantly higher in Hd McKrae-infected corneas as compared with Ld McKrae-infected corneas at 3 and 5 dpi. No significant corneal opacity, neovascularization, blepharitis, and epitheliopathy were observed in naïve or sham-infected mice. Higher viral titers were detected in corneas (1 and 3 dpi) and trigeminal ganglia (TG) (3 and 5 dpi) in Hd versus Ld KOS-63 groups (p < 0.05). Leukocyte density showed a gradual increase over time from 1 to 7 dpi in both KOS-63 and McKrae-infected corneas. Corneal flow cytometric analysis (3 dpi) demonstrated a higher percentage of Gr-1 + (71.6 vs. 26.3) and CD11b + (90.6 vs. 41.1) cells in Hd versus Ld KOS-63 groups. Corneal nerve density significantly decreased in both Hd KOS-63 and Hd McKrae infected corneas in comparison with naïve and sham-infected corneas. At 3 dpi corneal nerve density was lower in the Hd versus Ld KOS-63 groups (16.79 vs. 57.41 mm/mm2; p = 0.004). Corneal sensation decreased accordingly at 5 and 7 dpi in both Ld and Hd KOS-63-infected mice. Corneal inoculation with HSV-1 KOS-63 strain shows acute keratitis and nerve degeneration in a dose-dependent fashion, demonstrating virulence of this strain.Hamid-Reza MoeinVictor G. SendraArsia JamaliAhmad KheirkhahDeshea L. HarrisPedram HamrahNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hamid-Reza Moein Victor G. Sendra Arsia Jamali Ahmad Kheirkhah Deshea L. Harris Pedram Hamrah Herpes simplex virus-1 KOS-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis
description	Abstract To investigate the acute clinical, immunological, and corneal nerve changes following corneal HSV-1 KOS-63 strain inoculation. Corneas of C57BL/6 mice were inoculated with either low dose (Ld) or high dose (Hd) HSV-1 KOS-63 or culture medium. Clinical evaluation was conducted up to 7 days post inoculation (dpi). Viral titers were assessed by standard plaque assay. Excised corneas were stained for CD45 and beta-III tubulin. Corneal flow cytometry was performed to assess changes in leukocyte subpopulations. Corneal sensation was measured using a Cochet-Bonnet esthesiometer. Naïve, sham-infected (post scarification), and McKrae-infected C57BL/6 corneas served as two negative and positive controls, respectively. Compared to Ld infected mice, Hd HSV-1 KOS-63 demonstrated higher incidence of corneal opacity (1.5 ×) and neovascularization (2.6 × ; p < 0.05). At 7 dpi Hd infected mice showed more severe corneal opacity (2.23 vs. 0.87; p = 0.0003), neovascularization (6.00 vs. 0.75; p < 0.0001), and blepharitis (3.11 vs. 2.06; p = 0.001) compared to the Ld group. At 3 dpi epitheliopathy was significantly larger in the Hd group (23.59% vs. 3.44%; p = 0.001). Similarly, corneal opacity was significantly higher in Hd McKrae-infected corneas as compared with Ld McKrae-infected corneas at 3 and 5 dpi. No significant corneal opacity, neovascularization, blepharitis, and epitheliopathy were observed in naïve or sham-infected mice. Higher viral titers were detected in corneas (1 and 3 dpi) and trigeminal ganglia (TG) (3 and 5 dpi) in Hd versus Ld KOS-63 groups (p < 0.05). Leukocyte density showed a gradual increase over time from 1 to 7 dpi in both KOS-63 and McKrae-infected corneas. Corneal flow cytometric analysis (3 dpi) demonstrated a higher percentage of Gr-1 + (71.6 vs. 26.3) and CD11b + (90.6 vs. 41.1) cells in Hd versus Ld KOS-63 groups. Corneal nerve density significantly decreased in both Hd KOS-63 and Hd McKrae infected corneas in comparison with naïve and sham-infected corneas. At 3 dpi corneal nerve density was lower in the Hd versus Ld KOS-63 groups (16.79 vs. 57.41 mm/mm2; p = 0.004). Corneal sensation decreased accordingly at 5 and 7 dpi in both Ld and Hd KOS-63-infected mice. Corneal inoculation with HSV-1 KOS-63 strain shows acute keratitis and nerve degeneration in a dose-dependent fashion, demonstrating virulence of this strain.
format	article
author	Hamid-Reza Moein Victor G. Sendra Arsia Jamali Ahmad Kheirkhah Deshea L. Harris Pedram Hamrah
author_facet	Hamid-Reza Moein Victor G. Sendra Arsia Jamali Ahmad Kheirkhah Deshea L. Harris Pedram Hamrah
author_sort	Hamid-Reza Moein
title	Herpes simplex virus-1 KOS-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis
title_short	Herpes simplex virus-1 KOS-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis
title_full	Herpes simplex virus-1 KOS-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis
title_fullStr	Herpes simplex virus-1 KOS-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis
title_full_unstemmed	Herpes simplex virus-1 KOS-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis
title_sort	herpes simplex virus-1 kos-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9070c8e29edd4f1ab5b45e8ae1b6d68c
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Herpes simplex virus-1 KOS-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis

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