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Antimicrobial Agents and Chemotherapy, September 2003, p. 2914-2921, Vol. 47, No. 9
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.9.2914-2921.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Antiviral Effects of Geranylgeranylacetone: Enhancement of MxA Expression and Phosphorylation of PKR during Influenza Virus Infection

Masako Unoshima,1* Hideo Iwasaka,1 Junko Eto,2 Yoshiko Takita-Sonoda,2 Takayuki Noguchi,1 and Akira Nishizono2

Department of Anesthesiology,1 Department of Microbiology, Oita Medical University, Oita, Japan2

Received 20 November 2002/ Returned for modification 17 March 2003/ Accepted 24 June 2003

A cyclic polyisoprenoid compound, geranylgeranylacetone (GGA), has been used as antiulcer drug. GGA is also a potent inducer of heat shock proteins (HSPs). HSPs are considered to induce an antiviral effect; however, the detailed mechanism is unknown. To determine whether GGA might show antiviral activity and what the mechanism is, the effect of GGA against influenza virus (strain PR8) infection in vivo and in vitro was investigated. The results demonstrated that GGA treatment strongly suppressed the deleterious consequences of PR8 replication and was accompanied by an increase in HSP70 gene expression in mice. Results from in vitro analyses demonstrated that GGA significantly inhibited the synthesis of PR8-associated proteins and prominently enhanced expression of human myxovirus resistance 1 (MxA) followed by increased HSP70 transcription. Moreover, GGA augmented the expression of an interferon-inducible double-strand RNA-activated protein kinase (PKR) gene and promoted PKR autophosphorylation and concomitantly {alpha} subunit of eukaryotic initiation factor 2 phosphorylation during PR8 infection. It is proposed that GGA-induced HSP70 has potent antiviral activity by enhancement of antiviral factors and can clinically achieve protection from influenza virus infection.

* Corresponding author. Mailing address: Department of Anesthesiology, Oita Medical University, Idaigaoka 1-1, Hasama-machi, Oita 879-5593, Japan. Phone: 81-97-586-5943. Fax: 81-97-586-5949. E-mail: unomasa{at}oita-med.ac.jp.

Antimicrobial Agents and Chemotherapy, September 2003, p. 2914-2921, Vol. 47, No. 9
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.9.2914-2921.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Endo, S., Hiramatsu, N., Hayakawa, K., Okamura, M., Kasai, A., Tagawa, Y., Sawada, N., Yao, J., Kitamura, M. (2007). Geranylgeranylacetone, an Inducer of the 70-kDa Heat Shock Protein (HSP70), Elicits Unfolded Protein Response and Coordinates Cellular Fate Independently of HSP70. Mol. Pharmacol. 72: 1337-1348 [Abstract] [Full Text]  


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