IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on November 1, 2009
 (Investigative Ophthalmology and Visual Science. )
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.09-3752
This Article
Right arrow Full Text (P<P[PDF])
Right arrow All Versions of this Article:
iovs.09-3752v1
50/11/5419    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Michaelis, M.
Right arrow Articles by Cinatl, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Michaelis, M.
Right arrow Articles by Cinatl, J.

Article

Infection of human retinal pigment epithelial cells with influenza A viruses

Martin Michaelis 1, Janina Geiler 1, Denise Klassert 1, Hans Wilhelm Doerr 1, and Jindrich Cinatl 2*

1 Inst. f. Med. Virology, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany
2 Inst. f. Med. Virology, Johann Wolfgang Goethe-University Hospital, Paul-Ehrlich-Str. 40, Frankfurt, 60596, Germany

* To whom correspondence should be addressed. E-mail: cinatl{at}em.uni-frankfurt.de.


  Abstract

Purpose: Ocular involvement in influenza A virus diseases is common but usually limited to mild conjunctivitis. Seldomly, inflammation of the choriocapillaris may result in atrophia of the retinal pigment epithlium (RPE). Here, we infected primary human retinal pigment epithelial (RPE) cells with seasonal (H1N1 A/New Caledonia/20/99, H3N2 A/California/7/2004) or higly pathogenic avian H5N1 (A/Thailand/1(Kan-1)/04, A/Vietnam/1203/04, A/Vietnam/1194/04) influenza strains. Methods: Influenza A virus replication was studied by investigation of cytopathogenic effects, immune staining for influenza A virus nucleoprotein, determination of virus titres, and electron microscopy. Apoptosis induction was examined by immune staining for activated caspase 3 and cleaved PARP. Proinflammatory gene expression was investigated by quantitative PCR. Results: H5N1 but not seasonal influenza strains replicated to high titres (> 108 TCID50/ml) in RPE cells. H5N1 infection resulted in RPE cell apoptosis that was abolished by the antiviral drug ribavirin. Pre-treatment with type I interferons (interferon {alpha}, interferon {beta}) or the type II interferon interferon {gamma} inhibited H5N1 replication. Moreover, H5N1 infection induced expression of pro-inflammatory genes (tumour necrosis factor {alpha}, CXCL8, CXCL10, CXCL11, interleukin-6), which was inhibited by ribavirin in a concentration-dependent manner. Conclusions: We show a novel cell type derived from the central nervous system to be permissive to H5N1 influenza virus replication. This supports findings suggesting H5N1 influenza strains to own a greater potential to spread to non-respiratory tissues than seasonal "human" influenza viruses. Moreover, our data warrant to further study the role of influenza A virus replication in retinal pathologies associated with influenza A virus infections.

Key Words: retinal cell culture, retinal pigment epithelium, virus infection, influenza A virus, H5N1






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2009 by the Association for Research in Vision and Ophthalmology