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(Investigative Ophthalmology and Visual Science. 2006;47:645-651.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-1022
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West Nile Virus Infection Induces Interferon Signalling in Human Retinal Pigment Epithelial Cells

Jindrich Cinatl, Jr,1 Martin Michaelis,1 Corinna Fleckenstein,1 Gabriele Bauer,1 Hanka Kabicková,2 Martin Scholz,3 Holger F. Rabenau,1 and Hans Wilhelm Doerr1

1From the Institute for Medical Virology, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany; the 2KlinLab Stresovice, Prague, Czech Republic; and the 3Klinik für Unfall-und Handchirurgie, Heinrich Heine University, Düsseldorf, Germany.

PURPOSE. In addition to neuroinvasive disease, West Nile virus (WNV) infection is frequently associated with self-limiting chorioretinitis and vitritis. However, the mechanisms of ophthalmic WNV infection are rarely investigated, in part because of the lack of reliable in vitro models. The authors therefore established the first model of ocular WNV infection and investigated interaction of WNV with IFN signal-transduction mechanisms.

METHODS. Human retinal pigment epithelial (RPE) cells were infected with WNV strain NY385-99 at a multiplicity of infection of 5. Virus replication was evaluated by virus titers at different times after infection. The susceptibility of RPE cells to WNV infection was confirmed by transmission electron microscopy. IFN-ß expression was assessed by quantitative real-time PCR and by measurements of antiviral activity in cell culture supernatants. IFN signaling was evaluated by phosphorylation of transducer and activator of transcription 1 and 2 (STAT1/2) proteins, with immunoblot analysis.

RESULTS. RPE cells appeared to be highly sensitive to WNV infection. Maximum viral titers were found 24 hours after infection, followed by a continuous decline during the course of infection. WNV infection of RPE cells was followed by increased IFN-ß expression associated with IFN signaling and subsequent inhibition of WNV replication.

CONCLUSIONS. In this study, the first cell culture model of ophthalmic WNV infection was developed and characterized in RPE cells, and the molecular mechanisms of WNV infection were studied. The data suggest that WNV induces a general antiviral state in RPE cells. This general antiviral state correlates with WNV-induced IFN signaling in retinal cells.




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M. Michaelis, M. C. Kleinschmidt, H. W. Doerr, and J. Cinatl Jr
Minocycline inhibits West Nile virus replication and apoptosis in human neuronal cells
J. Antimicrob. Chemother., November 1, 2007; 60(5): 981 - 986.
[Abstract] [Full Text] [PDF]


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