Anti-adenoviral effect of anti-HIV agents in vitro in serotypes inducing keratoconjunctivitis.
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 CC(50) (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.
Uchio
Eiichi
E
Department of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. euchio@fukuoka-u.ac.jp
Fuchigami
Aki
A
Kadonosono
Kazuaki
K
Hayashi
Akio
A
Ishiko
Hiroaki
H
Aoki
Koki
K
Ohno
Shigeaki
S
D000258:Adenovirus Infections, Human / Q000188:drug therapy / Q000821:virology*; D000260:Adenoviruses, Human / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D003236:Conjunctivitis, Viral / Q000188:drug therapy / Q000821:virology*; D004279:DNA, Viral; D004847:Epithelial Cells / Q000821:virology; D018628:Gene Dosage; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014776:Virus Cultivation
D019380:Anti-HIV Agents; D004279:DNA, Viral