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Klin Monbl Augenheilkd 2002; 219(7): 477-486
DOI: 10.1055/s-2002-33587
Übersicht
© Georg Thieme Verlag Stuttgart · New York

Zur Pathogenese der herpetischen Keratitis

The pathogenesis of herpetic keratitisJustus  G.  Garweg1 , Markus  Halberstadt1
  • 1Universitäts-Augenklinik, Inselspital, Bern
Herzlichen Dank für die Übernahme der Druckkosten der Farbabbildungen an die Fa. GlaxoSmithKline AG, Talstr. 3 - 5, 3053 Münchenbuchsee, Schweiz
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Publication History

Eingegangen: 15. August 2001

Angenommen: 26. April 2002

Publication Date:
26 August 2002 (online)

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Zusammenfassung

Hintergrund: Infektionen mit Viren aus der Herpesfamilie gehören zu den häufigsten Virusinfektionen der Menschheit. Der wichtigste Vertreter dieser Gruppe ist das Herpes-simplex-Virus (HSV), dessen Typ 1 Erkrankungen vorwiegend oberhalb der Gürtellinie verursacht, während der Typ 2 häufiger Affektionen im Bereich des Urogenitaltraktes verursacht. Bei immunkompetentem Wirt ist die Vermehrung des Virus durch das rasche Einsetzen unspezifischer Abwehrmechanismen auf Haut und Schleimhäute beschränkt. Nach relativ kurzer Zeit werden diese durch eine spezifische, erworbene Immunantwort ergänzt. Mit dem Einsetzen der spezifischen Immunantwort geht die Erkrankung von einer aktivreplikativen Form in eine latente Form über. In einem bestimmten Prozentsatz der Fälle kommt es jedoch periodisch zur Reaktivierung der Infektion. Patienten: Bei okulärer Beteiligung nimmt mit der Anzahl der Rezidive die Wahrscheinlichkeit für eine Progredienz von einer epithelialen zu einer stromalen Keratitis (HSK) zu. Im Gegensatz zur epithelialen wird die stromale Keratitis im Wesentlichen als eine immunpathologische Erkrankung aufgefasst. Die HSK stellt eine der häufigsten Erblindungsursachen in der westlichen Welt dar. Ergebnisse: Die Mechanismen, die zur Entwicklung der HSK und zur Etablierung der viralen Latenz beim Menschen führen, sind größtenteils unbekannt. Aus Tiermodellen, insbesondere der Maus, und klinischen Studien gibt es Hinweise für eine zellvermittelte Immunantwort als wesentliche Ursache der Gewebsschädigung. Schlussfolgerung: Der Kenntnisstand über die verschiedenen Aspekte der Pathogenese der herpetischen Keratitis ist noch lückenhaft. Die aktuellen pathophysiologischen Vorstellungen, wie z. B. die einer virusinduzierten Autoimmunerkrankung, bilden die theoretische Grundlage für die modernen therapeutischen Strategien.

Abstract

Background: Viral infections of Herpes origin are the most commonly encountered ones in man. The most important member of this family is the Herpes simplex virus (HSV), two varieties of which are known to exist: HSV-1 affects predominantly the upper half of the body, whereas HSV-2 is associated mainly with diseases of the urogenital tract. In the immunocompetent host, viral replication is usually confined to cutaneous and mucocutaneous sites, invasion of subcutaneous tissues being impeded by an early onset of non-specific defence mechanisms. These are rapidly complemented by the specific, mainly cellular, immune response. Patients: Epithelial dendritic keratitis is the first symptomatic clinical finding, and after several recurrences, the corneal stroma may become involved. This condition of herpetic stromal keratitis (HSK), which, in contrast to the epithelial one, is believed to be directed by a predominantly immunopathological process, is one of the leading causes of infectious blindness in developed countries. Results: The mechanisms underlying HSK, and the establishment of viral latency and reactivation are poorly understood. But on the basis of studies with mice as well as clinical immunohistological observations, evidence is now accumulating in support of a cell-mediated mechanism being responsible for corneal destruction. Conclusion: Our present knowledge of the pathogenesis of herpetic keratitis is incomplete. The different pathophysiological aspects reflecting our current understanding, such as that of a virally induced autoimmune disease, form the basis of accepted clinical treatment concepts.

Schlüsselwörter

Herpes-Keratitis - HSK - Latenz - okuläre Virusinfektion - Immunpathogenese - Autoimmunerkrankung - ACAID

Key words

Herpetic keratitis - HSV-1 - recurrence - viral latency - ocular viral infection - immunopathogenesis - autoimmune disease - ACAID

Literatur

  • 1 Avery A C, Zhao Z S, Rodriquez A, Bikoff E K, Soheilian M, Foster C S, Cantor H. Resistance to herpes stromal keratitis conferred by an IgG2a derived peptide.  Nature. 1995;  376 431-434
    CrossrefPubMedSearch in Google Scholar
  • 2 Azumi A, Atherton S S. Sparing of the ipsilateral retina after anterior chamber inoculation of HSV-1: requirement for either CD4+ or CD8+ T cells.  Invest Ophthalmol Vis Sci. 1994;  35 3251-3259
    PubMedSearch in Google Scholar
  • 3 Azumi A, Cousins S W, Kanter M Y, Atherton S S. Modulation of murine herpes simplex virus type 1 retinitis in the uninoculated eye by CD4+ T lymphocytes.  Invest Ophthalmol Vis Sci. 1994;  35 54-63
    PubMedSearch in Google Scholar
  • 4 Babu J S, Kanangat S, Rouse B T. T cell cytokine mRNA expression during the course of the immunopathologic ocular disease-herpetic stromal keratitis.  J Immunol. 1995;  154 4822-4829
    PubMedSearch in Google Scholar
  • 5 Babu J S, Thomas J, Kanangat S, Morrison L A, Knipe D M, Rouse B T. Viral replication is required for induction of ocular immunopathology by herpes simplex virus.  J Virol. 1996;  70 101-107
    PubMedSearch in Google Scholar
  • 6 Biswas S, Suresh P, Bonshek R E, Corbitt G, Tullo A B, Ridgway A E. Graft failure in human donor corneas due to transmission of herpes simplex virus.  Br J Ophthalmol. 2000;  84 701-705
    CrossrefPubMedSearch in Google Scholar
  • 7 Boehnke M, Garweg J G, Germann D. Spontaneous endothelial necrosis in human donor cornea. New Orleans, La, USA; International Conference on Herpetic Eye Disease 1992 Abstract
    Search in Google Scholar
  • 8 Bouley D M, Kanangat S, Wire W, Rouse B T. Characterization of herpes simplex virus type-1 infection and herpetic stromal keratitis development in IFN-gamma knock-out mice.  J Immunol. 1995;  155 3964-3971
    PubMedSearch in Google Scholar
  • 9 Brik D, Dunkel E, Pavan-Langstone D. Herpetic keratitis: persistance of viral particles despite topical and systemic antiviral therapy.  Arch Ophthalmol. 1993;  111 522-527
    PubMedSearch in Google Scholar
  • 10 Buchmeier M J, Welsh R M, Dutko F J, Oldstone M BA. The virology and immunobiology of lymphocytic choriomeningitis virus infection.  Adv Immunol. 1980;  30 275-331
    PubMedSearch in Google Scholar
  • 11 Cantin E M, Chen J, McNeal J, Willey D E, Openshaw H. Detection of herpes simplex virus DNA sequences in corneal transplant recipients by polymerase chain reaction assays.  Curr Eye Res. 1991;  10, Suppl 15-21
    PubMedSearch in Google Scholar
  • 12 Casanova J L, Romero P, Widmann C, Kourilsky P, Maryanski J L. T cell receptor genes in a series of class I major histocompatibility complex-restricted cytotoxic T lymphocyte clones specific for a Plasmodium berghei nonapeptide: implications for T cell allelic exclusion and antigen-specific repertoire.  J Exp Med. 1991;  174 1371-1383
    CrossrefPubMedSearch in Google Scholar
  • 13 Chen W, Tang Q, Hendricks R L. Ex vivo model of leukocyte migration into herpes simplex virus infected mouse corneas.  J Leukoc Biol. 1996;  60 167-173
    PubMedSearch in Google Scholar
  • 14 Cheng H, Tumpey T M, Staats H F, van Rooijen N, Oakes J E, Lausch R N. Role of macrophages in restricting herpes simplex virus type 1 growth after ocular infection.  Invest Ophthalmol Vis Sci. 2000;  41 1402-1409
    PubMedSearch in Google Scholar
  • 15 Chun S, Daheshia M, Lee S, Rouse B T. Immune modulation by IL-10 gene transfer via viral vector and plasmid DNA: Implication for gene therapy.  Cell Immunol. 1999;  194 194-204
    CrossrefPubMedSearch in Google Scholar
  • 16 Cleator G M, Klapper P E, Dennett C, Sullivan A L, Bonshek R E, Marcyniuk B, Tullo A B. Corneal donor infection by herpes simplex virus: herpes simplex virus DNA in donor corneas.  Cornea. 1994;  13 294-304
    PubMedSearch in Google Scholar
  • 17 Cockerham G C, Krafft A E, McLean I W. Herpes simplex virus in primary graft failure.  Arch Ophthalmol. 1997;  115 586-589
    CrossrefPubMedSearch in Google Scholar
  • 18 Cockerham G C, Bijwaard K, Sheng Z M, Hidayat A A, Font R L, McLean I W. Primary graft failure: a clinicopathologic and molecular analysis.  Ophthalmology. 2000;  107 2083-2090
    CrossrefPubMedSearch in Google Scholar
  • 19 Cook S D, Hill J H. Herpes simplex virus: molecular biology and the possibility of corneal latency.  Surv Ophthalmol. 1991;  36 140-148
    CrossrefPubMedSearch in Google Scholar
  • 20 Corey L, Adams H G, Brown Z A, Holmes K K. Genital herpes simplex virus infections: clinical manifestations, course and complications.  Ann Intern Med. 1983;  98 958-972
    CrossrefPubMedSearch in Google Scholar
  • 21 Daheshia M, Kuklin N, Kanangat S, Manickan E, Rouse B T. Suppression of ongoing ocular inflammatory disease by topical administration of plasmid DNA encoding IL-10.  J Immunol. 1997;  159 1945-1952
    PubMedSearch in Google Scholar
  • 22 Dawson C R, Togni B. Herpes simplex eye infections: clinical manifestations, pathogenesis and management.  Surv Ophthalmol. 1976;  21 121-135
    PubMedSearch in Google Scholar
  • 23 Deshpande S P, Kumaraguru U, Rouse B T. Why do we lack an effective vaccine against herpes simplex virus infections?.  Microbes Infect. 2000;  2 973-978
    CrossrefPubMedSearch in Google Scholar
  • 24 Doerig C, Pizer L I, Wilcox C L. An antigen encoded by the latency-associated transcript in neuronal cell cultures latently infected with herpes simplex virus type 1.  J Virol. 1991;  65 2724-2727
    PubMedSearch in Google Scholar
  • 25 Doymaz M Z, Rouse B T. Herpetic stromal keratitis: an immunopathological disease mediated by CD4+ T lymphocytes.  Invest Ophthalmol Vis Sci. 1992;  33 2165-2173
    PubMedSearch in Google Scholar
  • 26 Eastlund T. Infectious disease transmission through cell, tissue, and organ transplantation: reducing the risk through donor selection.  Cell Transplant. 1995;  4 455-477
    PubMedSearch in Google Scholar
  • 27 Efstathiou S, Minson A C, Field H J, Anderson J R, Wildy P. Detection of herpes simplex virus-specific DNA sequences in latently infected mice and humans.  J Virol. 1986;  57 446-455
    PubMedSearch in Google Scholar
  • 28 Gangappa S, Manickan E, Rouse B T. Control of herpetic stromal keratitis using CTLA4Ig fusion protein.  Clin Immunol Immunopathol. 1998;  86 88-94
    CrossrefPubMedSearch in Google Scholar
  • 29 Garcia-Blanco M A, Cullen B R. Molecular basis of latency in pathogenic human viruses.  Science. 1991;  254 815-820
    PubMedSearch in Google Scholar
  • 30 Garweg J, Boehnke M. Slow viral replication of HSV-1 is responsible for early recurrence of herpetic keratitis after corneal grafting.  Graefe's Arch Clin Exp Ophthalmol. 1996;  234, Suppl 133-138
    PubMedSearch in Google Scholar
  • 31 Garweg J G, Boehnke M. Low rate shedding of HSV-1 DNA, but not of infectious virus from human donor corneae into culture media.  J Med Virol. 1997;  52 320-325
    CrossrefPubMedSearch in Google Scholar
  • 32 Geiger K, Howes E, Gallina M, Huang X J, Travis G H, Sarvetnick N. Transgenic mice expressing IFN-gamma in the retina develop inflammation of the eye and photoreceptor loss.  Invest Ophthalmol Vis Sci. 1994;  35 2667-2681
    PubMedSearch in Google Scholar
  • 33 Ghiasi H, Cai S, Slanina S M, Perng G C, Nesburn A B, Wechsler S L. The role of interleukin (IL)-2 and IL-4 in herpes simplex virus type 1 ocular replication and eye disease.  J Infect Dis. 1999;  179 1086-1093
    CrossrefPubMedSearch in Google Scholar
  • 34 He X, Treacy M N, Simmons D M, Ingraham H A, Swanson L W, Rosenfeld M G. Expression of a large family of POU-domain regulatory genes in mammalian brain development.  Nature. 1989;  340 35-41
    CrossrefPubMedSearch in Google Scholar
  • 35 Heiligenhaus A, Steuhl K P. Treatment of HSV-1 stromal keratitis with topical cyclosporin A: a pilot study.  Graefe's Arch Clin Exp Ophthalmol. 1999;  237 435-438
    CrossrefPubMedSearch in Google Scholar
  • 36 Hendricks R L, Tumpey T M. Contribution of virus and immune factors to herpes simplex virus type I induced corneal pathology.  Invest Ophthalmol Vis Sci. 1990;  31 1929-1939
    PubMedSearch in Google Scholar
  • 37 Hendricks R L, Tumpey T M, Finnegan A. IFN-gamma and IL-2 are protective in the skin but pathologic in the corneas of HSV-1 infected mice.  J Immunol. 1992;  149 3023-3028
    PubMedSearch in Google Scholar
  • 38 Herpetic Eye Disease Study Group . Oral acyclovir for herpes simplex virus eye disease.  Arch Ophthalmol. 2000;  118 1030-1036
    PubMedSearch in Google Scholar
  • 39 Herpetic Eye Disease Study Group . Psychological stress and other potential triggers for recurrences of herpes simplex virus eye infections.  Arch Ophthalmol. 2000;  118 1617-1625
    PubMedSearch in Google Scholar
  • 40 Hill J M, Sedarati F, Javier R T, Wagner E K, Stevens J G. Herpes simplex virus latent phase transcription facilitates in vivo reactivation.  Virology. 1990;  174 117-125
    CrossrefPubMedSearch in Google Scholar
  • 41 Hill T J. Herpes simplex virus latency. In: Roizman B (ed) The Herpes Viruses. New York; Plenum 1985 1st ed: 175-240
    Search in Google Scholar
  • 42 Holbach L M, Font R L, Naumann G OH. Herpes simplex stromal and endothelial keratitis. Granulomatous cell reactions at the level of Descemet's membrane, the stroma, and Bowman's layer.  Ophthalmology. 1990;  97 722-728
    CrossrefPubMedSearch in Google Scholar
  • 43 Holbach L M, Font R L, Beahr W, Pittler S J. HSV-antigens and HSV-DNA in avascular and vascularized lesions of human herpes simplex keratitis.  Curr Eye Res. 1991;  10, Suppl 63-68
    PubMedSearch in Google Scholar
  • 44 Holbach L M, Font R L, Wilhelmus K R. Recurrent herpes simplex keratitis with concurrent epithelial and stromal involvement. Immunohistochemical and ultrastructural observations.  Arch Ophthalmol. 1991;  109 692-695
    PubMedSearch in Google Scholar
  • 45 Hu M, Dutt J, Arrunatequi-Correa V, Baltatzis S, Foster C S. Cytokine mRNA in BALB/c mouse corneas infected with herpes simplex virus.  Eye. 1999;  13 309-313
    PubMedSearch in Google Scholar
  • 46 Inoue T, Inoue Y, Hayashi K, Yoshida A, Nishida K, Shimomura Y, Fujisawa Y, Aono A, Tano Y. Topical administration of HSV gD-IL-2 DNA is highly protective against murine herpetic stromal keratitis.  Cornea. 2002;  21 106-110
    CrossrefPubMedSearch in Google Scholar
  • 47 Jaeschke H, Smith C W. Mechanisms of neutrophil induced parenchymal cell injury.  J Leukoc Biol. 1997;  61 647-653
    PubMedSearch in Google Scholar
  • 48 Jones B R, Fison P N, Cobo M L. et al . Efficacy of acycloguanosine (Wellcome 248u) against herpes simplex ulceration.  Lancet. 1979;  1 243-244
    PubMedSearch in Google Scholar
  • 49 Kanangat S, Thomas J, Gangappa S, Babu J, Rouse B T. Herpes simplex virus type 1-mediated upregulation of IL-12 (p40) mRNA expression. Implications in immunopathogenesis and protection.  J Immunol. 1996;  156 1110-1116
    PubMedSearch in Google Scholar
  • 50 Keadle T L, Usui N, Laycock K A, Kumano Y, Pepose J S, Stuart P M. Cytokine expression in murine corneas during recurrent herpetic stromal keratitis.  Ocul Immunol Inflamm. 2001;  9 193-205
    PubMedSearch in Google Scholar
  • 51 Kemp L M, Dent C L, Latchman D S. Octamer motif mediates transcriptional repression of HSV immediate-early genes and octamer-containing cellular promoters in neuronal cells.  Neuron. 1990;  4 215-222
    CrossrefPubMedSearch in Google Scholar
  • 52 Kristie T M, LeBowitz J H, Sharp P A. The octamer-binding proteins from multi-protein-DNA complexes with the HSV alpha TIF regulatory protein.  EMBO J. 1989;  8 4229-4238
    PubMedSearch in Google Scholar
  • 53 Ksander B R, Hendricks R L. Cell-mediated immune tolerance to HSV-1 antigens associated with reduced susceptibility to HSV-1 corneal lesions.  Invest Ophthalmol Vis Sci. 1987;  28 1986-1993
    PubMedSearch in Google Scholar
  • 54 Labetoulle M, Kucera P, Ugolini G, Lafay F, Frau E, Offret H, Flamand A. Neuronal pathsways for the propagation of herpes simplex virus type 1 from one retina to the other in a murine model.  J Gen Virol. 2000;  81 1201-1210
    PubMedSearch in Google Scholar
  • 55 Liesegang T J. Epidemiology of ocular herpes simplex. Incidence in Rochester, Minn; 1950 through 1982.  Arch Ophthalmol. 1989;  107 1155-1159
    CrossrefPubMedSearch in Google Scholar
  • 56 Liesegang T J, Melton L J, Daly P J, Ilstrup D M. Epidemiology of ocular herpes simplex. Natural history in Rochester, Minn; 1950 through 1982.  Arch Ophthalmol. 1989;  107 1160-1165
    CrossrefPubMedSearch in Google Scholar
  • 57 Liesegang T J. Classification of herpes simplex virus keratitis and anterior uveitis.  Cornea. 1999;  18 127-143
    CrossrefPubMedSearch in Google Scholar
  • 58 Lopez C. Resistance to herpes simplex virus-type 1 (HSV-1).  Curr Top Microbiol Immunol. 1981;  92 15-24
    PubMedSearch in Google Scholar
  • 59 Lopez C, Kirkpatrick D, Read S E, Fitzgerald P A, Pitt J, Pahwa S, Ching C Y, Smithwick E M. Correlation between low natural killing of fibroblasts infected with herpes simplex virus type-1 and susceptibility to herpesvirus infections.  J Infect Dis. 1983;  147 1030-1035
    PubMedSearch in Google Scholar
  • 60 Maertzdorf J, van der Lelij A, Baarsma G S, Osterhaus A D, Verjans G M. Herpes simplex virus type 1 (HSV-1)-induced retinitis following herpes simplex encephalitis: implications for brain-to-eye transission of HSV-1.  Ann Neurol. 2000;  49 104-106
    PubMedSearch in Google Scholar
  • 61 Manickan E, Rouse R J, Yu Z, Wire W S, Rouse B T. Genetic immunization against herpes simplex virus. Protection is mediated by CD4+ T cells.  J Immunol. 1995;  155 259-265
    PubMedSearch in Google Scholar
  • 62 Mannis M J, Plotnik R D, Schwab I R, Newton R D. Herpes simplex dendritic keratitis after keratoplasty.  Am J Ophthalmol. 1991;  111 480-484
    PubMedSearch in Google Scholar
  • 63 Matsubara S, Atherton S S. Spread of HSV-1 to the suprachiasmatic nuclei and retina in T cell depleted BALB/c mice.  J Neuroimmunol. 1997;  80 165-171
    CrossrefPubMedSearch in Google Scholar
  • 64 Mercadal C, Bouley D M, DeStephano D, Rouse B T. Herpetic stromal keratitis in the reconstituted SCID mouse model.  J Virol. 1993;  67 3404-3408
    PubMedSearch in Google Scholar
  • 65 Mester J C, Milligan G N, Bernstein D I. Immunology of herpes simplex virus. In: Stanberry LR (ed) Genital and Neonatal Herpes. New York; Wiley 1996: 49-91
    Search in Google Scholar
  • 66 Metcalf J F, Hamilton D S, Reichert R W. Herpetic keratitis in athymic (nude) mice.  Infect Immunol. 1979;  26 1164-1171
    PubMedSearch in Google Scholar
  • 67 Meyers R L, Chitjian P A. Immunology of herpesvirus infection: immunity to herpes simplex virus in eye infections.  Surv Ophthalmol. 1976;  21 194-204
    PubMedSearch in Google Scholar
  • 68 Meyers-Elliott R H, Chitjian P A. Immunopathogenesis of corneal inflammation in herpes simplex virus stromal keratitis: role of the polymorphnuclear leukocyte.  Invest Ophthalmol Vis Sci. 1981;  20 784-798
    PubMedSearch in Google Scholar
  • 69 Miller J K, Laycock K A, Nash M M, Pepose J S. Corneal Langerhans cell dynamics after herpes simplex virus reactivation.  Invest Ophthalmol Vis Sci. 1993;  34 2282-2290
    PubMedSearch in Google Scholar
  • 70 Minamoto S, Treisman J, Hankins W D, Sugamura K, Rosenberg S A. Acquired erythropoietin responsiveness of interleukin-2 dependent T lymphocytes retrovirally transduced with genes encoding chimeric erythropoietin/interleukin-2 receptors.  Blood. 1995;  86 2281-2287
    PubMedSearch in Google Scholar
  • 71 Missotten L. Immunology and herpetic keratitis.  Eye. 1994;  8 12-21
    PubMedSearch in Google Scholar
  • 72 Morris D J, Cleator G M, Klapper P E, Cooper R J, Biney E O, Dennett C, Marcyniuk B, Tullo A B. Detection of herpes simplex virus DNA in donor cornea culture medium by polymerase chain reaction.  Br J Ophthalmol. 1996;  80 654-657
    PubMedSearch in Google Scholar
  • 73 Nathan C, Xie Q. Nitric Oxide syntheses: Roles, tolls, and controls.  Cell. 1994;  78 915-918
    CrossrefPubMedSearch in Google Scholar
  • 74 Neufeld M V, Steinemann T L, Merin L M, Stroop W G, Brown M F. Identification of a herpes simplex virus-induced dendrite in an eye-bank donor cornea.  Cornea. 1999;  18 489-492
    PubMedSearch in Google Scholar
  • 75 Newell C K, Martin S, Sendele D, Mercadal C M, Rouse B T. Herpes simplex virus induced stromal keratitis: role of T lymphocyte subsets in immunopathology.  J Virol. 1989;  63 769-775
    PubMedSearch in Google Scholar
  • 76 Newell C K, Sendele D, Rouse B T. Effects of CD4+ and CD8+ T-lymphocyte depletion on the induction and expression of herpes simplex stromal keratitis.  Reg Immunol. 1989;  2 366-369
    PubMedSearch in Google Scholar
  • 77 Nicholls S M, Shimeld C, Easty D L, Hill T J. Recurrent herpes simplex after corneal transplantation in rats.  Invest Ophthalmol Vis Sci. 1996;  37 425-435
    PubMedSearch in Google Scholar
  • 78 Niemialtowski M G, Rouse B T. Phenotype and functional studies on ocular T cells during herpetic infection of the eye.  J Immunol. 1992;  149 1864-1870
    PubMedSearch in Google Scholar
  • 79 Niemialtowski M G, Rouse B T. Predominance of Th1 cells in ocular tissue during herpetic stromal keratitis.  J Immunol. 1992;  149 3035-3039
    PubMedSearch in Google Scholar
  • 80 Openshaw H, McNeill J I, Lin X H, Niland J, Cantin E M. Herpes simplex virus DNA in normal corneas: persistence without viral shedding from ganglia.  J Med Virol. 1995;  46 75-80
    PubMedSearch in Google Scholar
  • 81 Pepose J S. Herpes simplex keratitis: role of viral infection versus immune response.  Surv Ophthalmol. 1991;  35 345-352
    PubMedSearch in Google Scholar
  • 82 Pepose J S, Leib D A, Stuart P M, Easty D L. Herpes simplex virus diseases: anterior segment of the eye. In: Pepose JS, Holland GN, Wilhelmus KR (eds) Ocular Infection and Immunity. St. Louis, MO; Mosby 1996: 905-932
    Search in Google Scholar
  • 83 Rasmussen L, Merigan T C. Role of T-lymphocytes in cellular immune responses during herpes simplex virus infection in humans.  Proc Natl Acad Sci USA. 1978;  8 3957-3961
    PubMedSearch in Google Scholar
  • 84 Remeijer L, Doornenbal P, Geerards A J, Rijneveld W A, Beekhuis W H. Newly acquired herpes simplex virus keratitis after penetrating keratoplasty.  Ophthalmology. 1997;  104 648-652
    PubMedSearch in Google Scholar
  • 85 Remeijer L, Maertzdorf J, Doornenbal P, Verjans G M, Osterhaus A D. Herpes simplex virus 1 transmission through corneal transplantation (Letter).  Lancet. 2001;  357 442
    CrossrefPubMedSearch in Google Scholar
  • 86 Rouse B T. Virus induced immunopathology.  Adv Virus Res. 1996;  47 353-376
    PubMedSearch in Google Scholar
  • 87 Russell R G, Nasisse M P, Larsen H S, Rouse B T. Role of T-lymphocytes in the pathogenesis of herpetic stromal keratitis.  Invest Ophthalmol Vis Sci. 1984;  25 938-944
    PubMedSearch in Google Scholar
  • 88 Sarvetnick N, Shizuru J, Liggitt D, Martin L, McIntyre B, Gregory A, Parslow T, Stewart T. Loss of pancreatic islet tolerance induced by beta-cell expression of interferon-gamma.  Nature. 1990;  346 844-847
    CrossrefPubMedSearch in Google Scholar
  • 89 Schmid D S, Rouse B T. The role of T cell immunity in control of herpes simplex virus.  Curr Top Microbiol Immunol. 1992;  179 57-74
    PubMedSearch in Google Scholar
  • 90 Sears A E, Hukkanen V, Labow M A, Levine A J, Roizman B. Expression of herpes simplex virus 1 alpha transinducing factor (VP16) does not induce reactivation of latent virus or prevent the establishment of latency in mice.  J Virol. 1991;  65 2929-2935
    PubMedSearch in Google Scholar
  • 91 Sengler U, Reinhard T, Adams O, Krempe C, Sundmacher R. Herpes simplex virus infection in the media of donor corneas during organ culture: frequency and consequences.  Eye. 2001;  15 644-647
    CrossrefPubMedSearch in Google Scholar
  • 92 Spencer W H, Hayes T L. Scanning and transmission electron microscopic observations of the topographic anatomy of dendritica lesions in the rabbit cornea.  Invest Ophthalmol Vis Sci. 1970;  9 183-195
    PubMedSearch in Google Scholar
  • 93 Steiner I, Spivack J G, Lirette R P, Brown S M, MacLean A R, Subak-Sharpe J H, Fraser N W. Herpes simplex virus type 1 latency-associated transcripts are evidently not essential for latent infection.  EMBO J. 1989;  8 505-511
    PubMedSearch in Google Scholar
  • 94 Steinman L. Some misconceptions about understanding autoimmunity through experiments with knockouts.  J Exp Med. 1997;  185 2039-2041
    CrossrefPubMedSearch in Google Scholar
  • 95 Stevens J G, Wagner E K, Devi-Rao G B, Cook M L, Feldman L T. RNA complementary to a herpes virus alpha gene mRNA is prominent in latently infected neurones.  Science. 1987;  235 1056-1059
    PubMedSearch in Google Scholar
  • 96 Strauss S. Clinical and biological differences between recurrent herpes simplex virus and varicella-zoster virus infection.  JAMA. 1989;  262 3455
    CrossrefPubMedSearch in Google Scholar
  • 97 Streilein J W. Immune regulation and the eye: a dangerous compromise.  FASEB J. 1987;  1 199-208
    PubMedSearch in Google Scholar
  • 98 Streilein J W, Dana M R, Ksander B R. Immunity causing blindness: five different paths to herpes stromal keratitis.  Immunology Today. 1997;  18 443-449
    CrossrefPubMedSearch in Google Scholar
  • 99 Stumpf T H, Shimeld C, Easty D L, Hill T J. Cytokine production in a murine model of recurrent herpetic stromal keratitis.  Invest Ophthalmol Vis Sci. 2001;  42 372-378
    PubMedSearch in Google Scholar
  • 100 Su Y-H, Yan X-T, Oakes J E, Lausch R N. Protective antibody therapy is associated with reduced chemokine transcripts in herpes simplex virus type 1 corneal infection.  J Virol. 1996;  70 1277-1281
    PubMedSearch in Google Scholar
  • 101 Sundmacher R, Neumann-Haefelin D. Herpes simplex virus-positive and negative keratouveitis. In: Silverstein AM, O'Connor R (eds) Immunology and Immunopathology of the Eye. New York; Masson 1979: 225-229
    Search in Google Scholar
  • 102 Swyers J S, Lausch R N, Kaufman H E. Corneal hypersensitivity to herpes simplex.  Br J Ophthalmol. 1967;  51 843-846
    PubMedSearch in Google Scholar
  • 103 Tang Q, Hendricks R L. Interferon gamma regulates platelet endothelial cell adhesion molecule 1 expression and neutrophil infiltration into herpes simplex virus infected mouse corneas.  J Exp Med. 1996;  184 1435-1447
    CrossrefPubMedSearch in Google Scholar
  • 104 Tang Q, Chen W, Hendricks R L. Proinflammatory functions of IL-2 in herpes simplex virus corneal infection.  J Immunol. 1997;  158 1275-1283
    PubMedSearch in Google Scholar
  • 105 Teitelbaum C S, Streeten B W, Dawson C R. Histopathology of herpes simplex virus keratouveitis.  Curr Eye Res. 1987;  6 189-194
    PubMedSearch in Google Scholar
  • 106 Thomas J, Gangappa S, Kanangat S, Rouse B T. On the essential involvement of neutrophils in the immunpathological disease: herpetic stromal keratitis.  J Immunol. 1997;  158 1383-1391
    PubMedSearch in Google Scholar
  • 107 Tsumura K, Watanabe M, Sakata H. Cytotoxic T lymphocyte activity after intravitreal inoculation of herpes simplex virus type 1 in mice.  Ophthalmic Res. 1995;  27 32-36
    PubMedSearch in Google Scholar
  • 108 Tumpey T M, Elner V M, Chen S H, Oakes J E, Lausch R N. Interleukin-10 treatment can suppress stromal keratitis induced by herpes simplex virus type 1.  J Immunol. 1994;  153 2258-2265
    PubMedSearch in Google Scholar
  • 109 Tumpey T M, Chen S H, Oakes J E, Lausch R N. Neutrophil mediated suppression of virus replication after herpes simplex virus type 1 infection of the murine cornea.  J Virol. 1996;  70 898-904
    PubMedSearch in Google Scholar
  • 110 Tumpey T M, Cheng H, Cook D N, Smithies O, Oakes J E, Lausch R N. Absence of macrophage inflammatory protein-1α prevents the development of blinding herpes stromal keratitis.  J Virol. 1998;  72 3705-3710
    PubMedSearch in Google Scholar
  • 111 Tumpey T M, Cheng H, Yan X T, Oakes J E, Lausch R N. Chemokine synthesis in the HSV-1 infected cornea and its suppression by interleucin 10.  J Leukoc Biol. 1998;  63 486-492
    PubMedSearch in Google Scholar
  • 112 Verjans G M, Remeijer L, van Binnendijk R S, Cornelissen J G, Volker-Dieben H J, Baarsma S G, Osterhaus A D. Identification and characterization of herpes simplex virus-specific CD4+ T cells in corneas of herpetic stromal keratitis patients.  J Infect Dis. 1998;  177 484-488
    PubMedSearch in Google Scholar
  • 113 Verjans G M, Remeijer L, Mooy C M, Osterhaus A D. Herpes simplex virus-specific T cells infiltrate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive T cells.  Invest Ophthalmol Vis Sci. 2000;  41 2607-2612
    PubMedSearch in Google Scholar
  • 114 Wander A H, Centifanto Y M, Kaufman H E. Strain specificity of clinical isolates of herpes simplex virus.  Arch Ophthalmol. 1980;  98 1458-1461
    PubMedSearch in Google Scholar
  • 115 Weiner J M, Carroll N, Robertson I F. The granulomatous reaction in herpetic stromal keratitis: immunohistological and ultrastructural findings.  Aust N Z J Ophthalmol. 1985;  13 365-372
    PubMedSearch in Google Scholar
  • 116 Whitley R J. Herpes simplex viruses. In: Fields BN, Knipe DM, Howley P (eds) Field's Virology. Philadelphia, PA; Lippincott-Raven 1996: 2297-2342
    Search in Google Scholar
  • 117 Whittum J A, Niederkorn J Y, McCulley J P, Streilein J W. Intracameral inoculation of herpes simlex virus type 1 induces anterior chamber associated immune deviation.  Curr Eye Res. 1983;  2 691-697
    PubMedSearch in Google Scholar
  • 118 Wildy P, Gell P G. The host response to herpes simplex virus.  Br Med Bull. 1985;  41 86-91
    PubMedSearch in Google Scholar
  • 119 Wilhelmus K R, Gee L, Hauk W W. et al . Herpetic eye disease study: a controlled trial of topical corticosteroids for herpes simplex stromal keratitis.  Ophthalmology. 1994;  101 1883-1896
    PubMedSearch in Google Scholar
  • 120 Wilhelmus K R. The treatment of herpes simplex virus epithelial keratitis.  Trans Am Ophthalmol Soc. 2000;  98 505-532
    PubMedSearch in Google Scholar
  • 121 Yasukawa M, Zarling J M. Human cytotoxic T cell clones directed against herpes simplex virus infected cells. I. Lysis restricted by HLA class II MB and DR antigens.  J Immunol. 1984;  133 422-427
    PubMedSearch in Google Scholar
  • 122 Zhao Z S, Granucci F, Yeh L, Schaffer P A, Cantor H. Molecular mimicry by herpes simplex virus type-1: autoimmune disease after viral infection.  Science. 1998;  279 1344-1347
    CrossrefPubMedSearch in Google Scholar

Justus G. Garweg

Universitäts-Augenklinik · Inselspital

3010 Bern · Schweiz

Email: justus.garweg@insel.ch