Abstract
• Background
Different viruses have been reported to be involved in retinal diseases in animalsystems. In humans, herpes simplex virus and cytomegalovirus have been found to cause retinal disease. Most of the studied viruses are neurotropic. In this study, the in vitro susceptibility of human retinal pigment epithelial cells (RPEC) to representative members of different groups of human pathogenic viruses was investigated.
• Methods
Early cultures of RPE C — after two or three passages — were infected with the following viruses: herpes simplex virus (HSV) type 1, human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus types 1 and 7, measles virus, parainfluenza virus and coxsackie virus B3.
• Results
Cultures of RPE C could be infected with neurotropic viruses like HSV or measles virus as well as with typical respiratory viruses like parainfluenza or adenoviruses. Coxsackievirus, an enterovirus, replicated as well as human CMV whereas EBV and HHV-6, two lymphotropic viruses, failed to infect RPE.
• Conclusion
These findings suggest that a variety of viruses, including those causing rather common illnesses, might be capable of inducing retinal lesions under certain circumstances due to haematogenous spread during the course of viraemia.
Keywords: Herpes Simplex Virus, Measle, Retinal Pigment Epithelial Cell, Measle Virus, Respiratory Virus
References
- 1.Atherton SS, Newell Ck, Kanter MY, Cousins SW. Retinitis in euthymic mice following inoculation of murine cytomegalovirus (MCMV) via the supraciliary route. Curr Eye Res. 1991;10:667–677. doi: 10.3109/02713689109013858. [DOI] [PubMed] [Google Scholar]
- 2.Barenett LA, Fujinami RS. Molecular mimicry: a mechanism for autoimmune injury. FASEB J. 1992;6:840–844. doi: 10.1096/fasebj.6.3.1740233. [DOI] [PubMed] [Google Scholar]
- 3.Bielefeldt-Ohmann H. An oculo-cerebellar syndrome caused by congenital bovine viral diarrhoea virus infection. Acta Vet Scand. 1984;25:571–578. doi: 10.1186/BF03547277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Carrereas B, Griffin DE, Silverstein AM. Sindbis virus-induced ocular immunopathology. Invest Ophthalmol Vis Sci. 1982;22:571–578. [PubMed] [Google Scholar]
- 5.Del Cerro M, Grover DA, Monjan AA, Pfau CJ, Dermatte JE. Chronic retinitis in rats infected as neonates with lymphocytic choriomeningitis virus: a clinical, histopathologic, and electroretinographic study. Invest Ophthalmol Vis Sci. 1982;23:697–714. [PubMed] [Google Scholar]
- 6.Dolivo M, Kucera P, Bommeli W. Progression of the rabies virus in the visual system of the rat. Comp Immunol Microbiol Infect Dis. 1982;5:67–69. doi: 10.1016/0147-9571(82)90016-9. [DOI] [PubMed] [Google Scholar]
- 7.Dutt K, York D, Kaplan HJ, Semple E, Verly G, Srinivasan A. Replication of HIV in human fetal retinal cultures and established pigment epithelial cell lines. Invest Ophthalmol Vis Sci. 1989;30:1535–1541. [PubMed] [Google Scholar]
- 8.Egbert PR, Pollard RB, Gallagher JG, et al. Cytomegalovirus retinitis in immunosuppressed hosts. II. Ocular manifestations. Ann Int Med. 1980;93:664–670. doi: 10.7326/0003-4819-93-5-664. [DOI] [PubMed] [Google Scholar]
- 9.Flood MT, Gouras P, Kjeldbye H. Growth characteristics and ultrastructure of human retinal pigment epithelium in vitro. Invest Ophthalmol Vis Sci. 1980;19:1309–1320. [PubMed] [Google Scholar]
- 10.Forrester JV, McMenamin PG, Holthouse I, Lumsden L, Liversidge J. Localization and characterization of major histocompatibility complex class II-positive cells in the posterior segment of the eye: implications for induction of autoimmune uveoretinitis. Invest Ophthalmol Vis Sci. 1994;35:64–77. [PubMed] [Google Scholar]
- 11.Fukushima A, Ueno H, Fujimoto S. Antigenic cross-reactivity between human T lymphotropic virus type I (HTLV-I) and retinal antigens recognized by T cells. Clin Exp Immunol. 1994;95:459–464. doi: 10.1111/j.1365-2249.1994.tb07019.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Goldstein BG, Pavan PR. Retinal infiltrates in six patients with an associated viral syndrome. Retina. 1985;5:144–150. doi: 10.1097/00006982-198500530-00002. [DOI] [PubMed] [Google Scholar]
- 13.Greer CH. Bilateral necrotizing retinitis complication fatal encephalitis due to herpes simplex virus type 2. Ophthalmologica. 1980;180:146–150. doi: 10.1159/000308969. [DOI] [PubMed] [Google Scholar]
- 14.Grisanti S, Heimann K, Wiedemann P. Immune response to specific molecules of the retina in proliferative vitreoretinal disorders. Graefe's Arch Clin Exp Ophthalmol. 1994;232:302–307. doi: 10.1007/BF00194480. [DOI] [PubMed] [Google Scholar]
- 15.Grutzmacher RD, Henderson D, McDonald PJ, Coster DJ. Herpes simplex chorioretinitis in a healthy adult. Am J Ophthalmol. 1983;96:788–796. doi: 10.1016/s0002-9394(14)71925-7. [DOI] [PubMed] [Google Scholar]
- 16.Hansen LL. Retinale Erkrankungen bei AIDS. Ophthalmologe. 1993;90:239–249. [PubMed] [Google Scholar]
- 17.Helbig H, Kittredge KL, Coca-Prados M, Nussenblatt RB. Differentielle Expression von HLA DR, DP und DQ an kultivierten, menschlichen Ziliarkörperepithelzellen. Fortsch Ophthalmol. 1991;88:295–298. [PubMed] [Google Scholar]
- 18.Hooks JJ, Percopo C, Wang Y, Detrick B. Retina and retinal pigment epithelial cell autoantibodies are produced during routine coronavirus retinopathy. J Immunol. 1993;151:3381–3389. [PubMed] [Google Scholar]
- 19.Huemer HP, Bröker M, Larcher C, Lambris JD, Dierich MP. The central segment of herpes simplex virus type 1 glycoprotein C (gC) is not involved in C3b binding: demonstration by using monoclonal antibodies and recombinant gC expressed in Escherichia coli. J Gen Virol. 1989;70:1571–1578. doi: 10.1099/0022-1317-70-6-1571. [DOI] [PubMed] [Google Scholar]
- 20.Konda BR, Pararajasegaram G, Wu GS, Stanforth D, Rao NA. Role of retinal pigment epithelium in the development of experimental autoimmune uveitis. Invest Ophthalmol Vis Sci. 1994;35:40–47. [PubMed] [Google Scholar]
- 21.Krey H, Ludwig H, Gierend M. Borna disease virus-induced retinouveitis treated with immunosuppressive drugs. Albrecht von Graefes Arch Klin Exp Ophthalmol. 1981;216:111–119. doi: 10.1007/BF00414578. [DOI] [PubMed] [Google Scholar]
- 22.Laatikainen L, Immonen I. Multiple evanescent white dot syndrome. Greafes Arch Clin Exp Ophthalmol. 1988;226:37–40. doi: 10.1007/BF02172715. [DOI] [PubMed] [Google Scholar]
- 23.Liebowitz D, Kieff E. EpsteinBarr virus. In: Roizman B, Whitley RD, Lopez C, editors. The human herpesviruses. New York: Raven Press; 1993. pp. 107–172. [Google Scholar]
- 24.Lundh B. Spread of vesicular stomatitis virus along the visual pathways after retinal infection in the mouse. Acta Neuropathol (Berl) 1990;79:395–401. doi: 10.1007/BF00308715. [DOI] [PubMed] [Google Scholar]
- 25.Merges MJ, Whittum-Hudson JA. In vitro susceptibility of newborn murine retinal cells to herpes simplex virus type 1 infection. Invest Ophthalmol Vis Sci. 1990;31:1224–1230. [PubMed] [Google Scholar]
- 26.Parhard IM, Johnson KP, Wolinsky JS, Swoveland P. Measles retinopathy. A hamster model of acute and chronic lesions. Lab Invest. 1980;43:52–60. [PubMed] [Google Scholar]
- 27.Pathak S, Webb HE. An electron microscopical study of the replication of avirulent Semliki Forest virus in the retina of mice. J Neurol Sci. 1988;85:87–96. doi: 10.1016/0022-510x(88)90038-x. [DOI] [PubMed] [Google Scholar]
- 28.Percy DH, Coulter-Mackie M. Measles virus encephalitis and retinopathy in the Wistar rat. Exp Mol Pathol. 1982;36:435–446. doi: 10.1016/0014-4800(82)90072-7. [DOI] [PubMed] [Google Scholar]
- 29.Reid DM, Campbell AM, Forrester JV. EB-virus transformed human lymphocytes from uveitis and retinitis pigmentosa patients secrete antibodies to retinal antigens. J Clin Lab Immunol. 1988;26:107–111. [PubMed] [Google Scholar]
- 30.Robbins SG, Hamel CP, Detrick B, Hoojks JJ. Murine coronavirus induces an acute and long lasting disease of the retina. Lab Invest. 1990;64:417–426. [PubMed] [Google Scholar]
- 31.Robbins SG, Wiggert B, Kutty G, Chader GJ, Detrick B, Hooks JJ. Redistribution and reduction of interphotoreceptor retinoid-binding protein during ocular coronavirus infection. Invest Ophthalmol Vis Sci. 1992;33:60–67. [PubMed] [Google Scholar]
- 32.Roizman B, Sears AE. Herpes simplex viruses and their replication. In: Roizman B, Whitley RD, Lopez C, editors. The human herpesviruses. New York: Raven Press; 1993. pp. 11–68. [Google Scholar]
- 33.Rummelt V, Rummelt C, Jahn G, Wenkel H, Sinzger C, Mayer UM, Naumann GO. Triple retinal infection with human immunodeficiency virus type l, cytomegalovirus, and herpes simplex virus type 1. Light and electron microscopy, immunohistochemistry, and in situ hybridization. Ophthalmology. 1994;101:270–279. doi: 10.1016/s0161-6420(94)31336-4. [DOI] [PubMed] [Google Scholar]
- 34.Salahuddin SZ, Ablashi DV, Markham PD, et al. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science. 1986;234:596–601. doi: 10.1126/science.2876520. [DOI] [PubMed] [Google Scholar]
- 35.Schroeder CH, Engler H, Kirchner HJ. Protection of mice by a apathogenic strain of HSV 1 against lethal infection by a pathogenic strain of HSV type 1. J Gen Virol. 1981;52:159–161. doi: 10.1099/0022-1317-52-1-159. [DOI] [PubMed] [Google Scholar]
- 36.Shinohara T, Singh VK, Tsuda M, Yamaki K, Abe T, Suzuki S. Santigen: from gene to autoimmune uveitis. Exp Eye Res. 1990;50:751–757. doi: 10.1016/0014-4835(90)90125-e. [DOI] [PubMed] [Google Scholar]
- 37.Siam AL, Meegan JM. Ocular disease resulting from infection with Rift Valley fever virus. Trans R Soc Trop Med Hyg. 1980;74:539–541. doi: 10.1016/0035-9203(80)90074-7. [DOI] [PubMed] [Google Scholar]
- 38.Singh VK, Kalra HK, Yamaki K, Abe T, Donoso LA, Shinohara T. Molecular mimicry between a uveitopthogenic site of S-antigen and viral peptides. Induction of experimental autoimmune uveitis in Lewis rats. J Immunol. 1990;144:1282–1287. [PubMed] [Google Scholar]
- 39.Wang L, Kemp MC, Roy P, Collison EW. Tissue tropism and target cells of bluetongue virus in the chicken embryo. J Virol. 1988;62:887–893. doi: 10.1128/jvi.62.3.887-893.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Wang Y, Detrick B, Hooks JJ. Coronavirus (JHM) replication within the retina: analysis of cell tropism in mouse retinal cell cultures. Virology. 1993;193:124–137. doi: 10.1006/viro.1993.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Zierhut M, Tamesin R, Hemady R, Foster CS. Herpes-simplexVirus Retinitis. Rolle des Immunsystems im Tierversuch. Fortschr Ophthalmol. 1991;88:740–747. [PubMed] [Google Scholar]
- 42.Zierhut M, Soukasian S, Zhao TZ, Tamesis RR, Foster CS. Depletion of T-lymphocyte subsets in murine herpes-simplex-virus retinitis. German J Ophthalmol. 1992;1:145–150. [PubMed] [Google Scholar]