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Anti-adenoviral effect of anti-HIV agents in vitro in serotypes inducing keratoconjunctivitis

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Abstract

Background

Around one million people are affected by adenoviral keratoconjunctivitis a year in Japan, and it is recognized as one of the major pathogens of ophthalmological nosocomial infection worldwide. Although cidofovir can be used systemically for immunocompromised patients with disseminated adenoviral infection, no specific anti-adenoviral agent has been established for the treatment of adenoviral infection. We evaluated the anti-adenoviral effect of anti-HIV (human immunodeficiency virus) agents in this study.

Methods

Five anti-HIV agents (zalcitabine, stavudine, nevirapine, indinavir and amprenavir) were subjected to in vitro evaluation. A549 cells were used for viral cell culture, and adenovirus serotypes 3, 4, 8, 19 and 37 were used. After calculating CC50 (50% cytotoxic concentration) of each agent by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) method, we cultured adenovirus with the agents for seven days and quantitatively measured extracted adenoviral DNA by real-time PCR.

Results

Among the anti-HIV drugs, zalcitabine and stavudine, both nucleoside reverse transcriptase inhibitors, showed significant anti-adenoviral activity. In contrast, nevirapine, a non-nucleoside reverse transcriptase inhibitor, and indinavir and amprenavir, which are both protease inhibitors, were ineffective against adenovirus.

Conclusions

These results indicate that zalcitabine and stavudine are possible candidates for the local and systemic treatment of adenoviral infection, and the anti-adenoviral effect might depend on the pharmacological properties of anti-HIV agents. The chemical properties on the clinical safety for systemic and local application need to be determined in order to for these drugs to be accepted for the treatment of adenovirus in clinical settings.

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Acknowledgements

This work was supported by a Grant-in-Aid for Encouragement of Scientists (18591944) from the Ministry of Education, Science, Sports and Culture of Japan. We thank Dr. W. Gray for editing this manuscript.

The authors have no financial relationship with the organization that sponsored the research. The authors have full control of all primary data and agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review our data upon request.

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Authors and Affiliations

  1. Department of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

    Eiichi Uchio & Aki Fuchigami

  2. Department of Ophthalmology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan

    Kazuaki Kadonosono

  3. Mitsubishi Kagaku Bio-clinical Laboratories, Inc., 30-1 Shimura 3-chome, Itabashi-ku, Tokyo, 174-8555, Japan

    Akio Hayashi & Hiroaki Ishiko

  4. Department of Ophthalmology, Hokkaido University Graduate School of Medicine, 14 Jo Kita, 5 Nishi, Kita-ku, Sapporo, 060-0814, Japan

    Koki Aoki & Shigeaki Ohno

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  1. Eiichi Uchio
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  3. Kazuaki Kadonosono
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Correspondence to Eiichi Uchio.

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Uchio, E., Fuchigami, A., Kadonosono, K. et al. Anti-adenoviral effect of anti-HIV agents in vitro in serotypes inducing keratoconjunctivitis. Graefes Arch Clin Exp Ophthalmol 245, 1319–1325 (2007). https://doi.org/10.1007/s00417-006-0523-z

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  • DOI: https://doi.org/10.1007/s00417-006-0523-z

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