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Neuraminidase-producing oral mitis group streptococci potentially contribute to influenza viral infection and reduction in antiviral efficacy of zanamivir

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Abstract

Influenza is a serious respiratory disease among immunocompromised individuals, such as the elderly, and its prevention is an urgent social issue. Influenza viruses rely on neuraminidase (NA) activity to release progeny viruses from infected cells and spreading the infection. NA is, therefore, an important target of anti-influenza drugs. A causal relationship between bacteria and influenza virus infection has not yet been established, however, a positive correlation between them has been reported. Thus, in this study, we examined the biological effects of oral mitis group streptococci, which are predominant constituents of human oral florae, on the release of influenza viruses. Among them, Streptococcus oralis ATCC 10557 and Streptococcus mitis ATCC 6249 were found to exhibit NA activity and their culture supernatants promoted the release of influenza virus and cell-to-cell spread of the infection. In addition, culture supernatants of these NA-producing oral bacteria increased viral M1 protein expression levels and cellular ERK activation. These effects were not observed with culture supernatants of Streptococcus sanguinis ATCC 10556 which lacks the ability to produce NA. Although the NA inhibitor zanamivir suppressed the release of progeny viruses from the infected cells, the viral release was restored upon the addition of culture supernatants of NA-producing S. oralis ATCC 10557 or S. mitis ATCC 6249. These findings suggest that an increase in the number of NA-producing oral bacteria could elevate the risk of and exacerbate the influenza infection, hampering the efficacy of viral NA inhibitor drugs.

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Acknowledgments

This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; a grant from the Dental Research Center, Nihon University School of Dentistry, Tokyo; Nihon University President’s Grant for Specified Multidisciplinary Research; and the Strategic Research Base Development Program for Private Universities (S1001024) and Japan Initiative for Global Research Network on Infectious Diseases from the MEXT of Japan.

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Authors and Affiliations

  1. Department of Microbiology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan

    Noriaki Kamio, Kenichi Imai, Marni E. Cueno, Muneaki Tamura, Yuko Saito & Kuniyasu Ochiai

  2. Division of Immunology and Pathobiology, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan

    Noriaki Kamio, Kenichi Imai, Muneaki Tamura & Kuniyasu Ochiai

  3. Division of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Kazufumi Shimizu

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  1. Noriaki Kamio
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  2. Kenichi Imai
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  3. Kazufumi Shimizu
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  4. Marni E. Cueno
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  7. Kuniyasu Ochiai
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Correspondence to Kenichi Imai or Kuniyasu Ochiai.

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Kamio, N., Imai, K., Shimizu, K. et al. Neuraminidase-producing oral mitis group streptococci potentially contribute to influenza viral infection and reduction in antiviral efficacy of zanamivir. Cell. Mol. Life Sci. 72, 357–366 (2015). https://doi.org/10.1007/s00018-014-1669-1

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