Herpes keratitis

Rowe, Alexander M.; Leger, Anthony J. St.; Jeon, Seung Hyuck; Dhaliwal, D.K.; Knickelbein, Jared E.; Hendricks, Robert L.

doi:10.1016/j.preteyeres.2012.08.002

Cited by 251 publications

(264 citation statements)

References 198 publications

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“…We identified 122 novel O-glycosylation sites on 28 HCMV proteins, including gB, gH, gL, gN, and gO (Table 2 and supplemental Data Sets S1 and S4). Most of the identified glycoproteins had a relatively small number of sites (1)(2)(3)(4)(5)(6)(7)(8), with the exception of RL12 and UL22A, in which we found 18 and 14 sites, respectively. Five HCMV envelope glycoproteins are indispensable for replication: gB, gH, gL, gM, and gN (57).…”

Section: Mapping O-glycosites In Human Herpesvirusesmentioning

confidence: 56%

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus

Bagdonaite

Nordén

Joshi

et al. 2016

Journal of Biological Chemistry

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Herpesviruses are among the most complex and widespread viruses, infection and propagation of which depend on envelope proteins. These proteins serve as mediators of cell entry as well as modulators of the immune response and are attractive vaccine targets. Although envelope proteins are known to carry glycans, little is known about the distribution, nature, and functions of these modifications. This is particularly true for O-glycans; thus we have recently developed a "bottom up" mass spectrometry-based technique for mapping O-glycosylation sites on herpes simplex virus type 1. We found wide distribution of O-glycans on herpes simplex virus type 1 glycoproteins and demonstrated that elongated O-glycans were essential for the propagation of the virus. Here, we applied our proteome-wide discovery platform for mapping O-glycosites on representative and clinically significant members of the herpesvirus family: varicella zoster virus, human cytomegalovirus, and Epstein-Barr virus. We identified a large number of O-glycosites distributed on most envelope proteins in all viruses and further demonstrated conserved patterns of O-glycans on distinct homologous proteins. Because glycosylation is highly dependent on the host cell, we tested varicella zoster virus-infected cell lysates and clinically isolated virus and found evidence of consistent O-glycosites. These results present a comprehensive view of herpesvirus O-glycosylation and point to the widespread occurrence of O-glycans in regions of envelope proteins important for virus entry, formation, and recognition by the host immune system. This knowledge enables dissection of specific functional roles of individual glycosites and, moreover, provides a framework for design of glycoprotein vaccines with representative glycosylation.

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Section: Mapping O-glycosites In Human Herpesvirusesmentioning

confidence: 56%

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus

Bagdonaite

Nordén

Joshi

et al. 2016

Journal of Biological Chemistry

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“…13,31 Previously, we reported that HSV-1 causes regression of sensory fibers innervating the cornea and loss of their function during the acute phase of infection, followed by abnormal nerve regeneration at a time point consistent with establishment of viral latency. 23 Since 8 days pi, the time point pi of maximal observed loss of innervation, coincides with a highly inflammatory milieu in the infected cornea, 12,14 we hypothesized the mechanism triggering regression of corneal nerves is immune system mediated. To test this hypothesis, we evaluated the effects of DEX, a clinically prescribed, anti-inflammatory reagent, 25,26 on the corneal nerve network after HSV-1 infection.…”

Section: Dex Prevents Corneal Nerve Regression and Sensation Loss Aftmentioning

confidence: 99%

IL-6 Contributes to Corneal Nerve Degeneration after Herpes Simplex Virus Type I Infection

Chucair-Elliott

Jinkins

Carr

et al. 2016

The American Journal of Pathology

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Herpes simplex virus type 1 (HSV-1) is a leading cause of neurotrophic keratitis characterized by decreased corneal sensation because of damage to the corneal sensory fibers. We and others have reported regression of corneal nerves during acute HSV-1 infection. To determine whether denervation is caused directly by the virus or indirectly by the elicited immune response, mice were infected with HSV-1 and topically treated with dexamethasone (DEX) or control eye drops. Corneal sensitivity was measured using a Cochet-Bonnet esthesiometer and nerve network structure via immunohistochemistry. Corneas were assessed for viral content by plaque assay, leukocyte influx by flow cytometry, and content of chemokines and inflammatory cytokines by suspension array. DEX significantly preserved corneal nerve structure and sensitivity on infection. DEX reduced myeloid and T-cell populations in the cornea and did not affect viral contents at 4 and 8 days post infection. The elevated protein contents of chemokines and inflammatory cytokines on infection were greatly suppressed by DEX. Subconjunctival delivery of neutralizing antibody against IL-6 to infected mice resulted in partial preservation of corneal nerve structure and sensitivity. Our study supports a role for the immune response, but not local virus replication in the development of HSV-1einduced neurotrophic keratitis. IL-6 is one of the factors produced by the elicited inflammatory response to HSV-1 infection contributing to nerve regression.

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“…tory cytokines and chemokines that result in the recruitment of neutrophils and then various types of T cells into the cornea (21)(22)(23)(24). For some infections, like HSV infections, blood vessels and lymphatics infiltrate into the cornea, amplifying the response.…”

Section: Fig 9 Flow Cytometry Analysis Of T-cell Subsets In Infectedmentioning

confidence: 99%

Both CD8⁺and CD4⁺T Cells Contribute to Corneal Clouding and Viral Clearance following Vaccinia Virus Infection in C57BL/6 Mice

Larsen

Clausius

Kolb

et al. 2016

J Virol

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Vaccinia virus (VACV) keratitis is a serious complication following smallpox vaccination and can lead to blindness. The pathological mechanisms involved in ocular VACV infection are poorly understood. Previous studies have used rabbits, but the lack of immune reagents and transgenic or knockout animals makes them less suitable for mechanistic studies. We report that infection of C57BL/6 mice with 1 ؋ 10 7 PFU of vaccinia virus strain WR results in blepharitis, corneal neovascularization, and stromal keratitis. The DryVax strain of VACV was completely attenuated. Infection required corneal scarification and replication-competent virus, and the severity of ocular disease was similar in 4-to 6-week-old and 1-year-old mice. Viral titers peaked at approximately 1 ؋ 10 6 PFU on day 5 postinfection, and virus had not cleared by day 13 postinfection. Neutrophils were found in the peripheral cornea on day 1 after infection and then declined, followed by infiltration of both CD4؉ and CD8 ؉ T cells, which remained peripheral throughout the infection. Blood vessel growth extended 2 to 5 mm into the cornea from the limbus. Infection of CD4 ؊/؊ , CD8 ؊/؊ , or antibody-depleted mice resulted in similar disease severity and corneal clouding, indicating that both T-cell subsets were involved in the immunopathological response. Depletion of both CD4؉ and CD8 ؉ T cells resulted in significantly more severe disease and failure to clear the virus. On the basis of our results, the pathology of VACV keratitis is significantly different from that of herpes simplex virus keratitis. Further studies are likely to reveal novel information regarding virulence and immune responses to viral ocular infection. IMPORTANCEPotentially blinding eye infections can occur after vaccination for smallpox. Very little is known about the pathological mechanisms that are involved, and the information that is available was generated using rabbit models. The lack of immunological reagents for rabbits makes such studies difficult. We characterized a mouse model of vaccinia virus ocular disease using C57BL/6 mice and strain WR and show that both CD4؉ and CD8 ؉ T-cell subsets play a role in the blinding eye disease and in controlling virus replication. On the basis of these results, vaccinia virus keratitis is significantly different from herpes simplex virus keratitis, and further studies using this model should generate novel insights into immunopathological responses to viral ocular infection. In 1977, the World Health Organization reported the last known case of naturally acquired smallpox virus infection (1). The eradication of smallpox was accomplished by rigorous vaccination using vaccinia virus (VACV) and a contact tracing program. Shortly thereafter, the United States stopped vaccination of the general population. In response to increased terrorism incidents, including bioterror events, the U.S. government expanded the list of those who should be vaccinated to include first responders and stockpiled smallpox vaccine and vaccinia virus immune gl...

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Herpes keratitis

Cited by 251 publications

References 198 publications

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus

IL-6 Contributes to Corneal Nerve Degeneration after Herpes Simplex Virus Type I Infection

Both CD8⁺and CD4⁺T Cells Contribute to Corneal Clouding and Viral Clearance following Vaccinia Virus Infection in C57BL/6 Mice

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Herpes keratitis

Cited by 251 publications

References 198 publications

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus

IL-6 Contributes to Corneal Nerve Degeneration after Herpes Simplex Virus Type I Infection

Both CD8+and CD4+T Cells Contribute to Corneal Clouding and Viral Clearance following Vaccinia Virus Infection in C57BL/6 Mice

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Both CD8⁺and CD4⁺T Cells Contribute to Corneal Clouding and Viral Clearance following Vaccinia Virus Infection in C57BL/6 Mice