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Journal of Virology, April 2003, p. 4104-4112, Vol. 77, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.7.4104-4112.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Influenza A Virus-Infected Hosts Boost an Invasive Type of Streptococcus pyogenes Infection in Mice

Shigefumi Okamoto,1 Shigetada Kawabata,1,2* Ichiro Nakagawa,1 Yoshinobu Okuno,3 Toshiyuki Goto,4 Kouichi Sano,4 and Shigeyuki Hamada1

Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871,1 PRESTO, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012,2 Department of Virology, Osaka Prefectural Institute of Public Health, Osaka 537-0025,3 Department of Microbiology, Osaka Medical College, Takatsuki-Osaka 569-8686, Japan4

Received 27 August 2002/ Accepted 23 December 2002

The apparent worldwide resurgence of invasive Streptococcus pyogenes infection in the last two decades remains unexplained. At present, animal models in which toxic shock-like syndrome or necrotizing fasciitis is induced after S. pyogenes infection are not well developed. We demonstrate here that infection with a nonlethal dose of influenza A virus 2 days before intranasal infection with a nonlethal dose of S. pyogenes strains led to a death rate of more than 90% in mice, 10% of which showed necrotizing fasciitis. Infection of lung alveolar epithelial cells by the influenza A virus resulted in viral hemagglutinin expression on the cell surface and promoted internalization of S. pyogenes. However, treatment with monoclonal antibodies to hemagglutinin markedly decreased this internalization. Our results indicate that prior infection with influenza A virus induces a lethal synergism, resulting in the induction of invasive S. pyogenes infection in mice.

* Corresponding author. Mailing address: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879-2898. Fax: 81-6-6878-4755. E-mail: kawabata{at}dent.osaka-u.ac.jp.

Journal of Virology, April 2003, p. 4104-4112, Vol. 77, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.7.4104-4112.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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