b-Glucan Derived from Aureobasidium pullulans Is Effective for the Prevention of Influenza in Mice
Daisuke Muramatsu1,3, Atsushi Iwai2,3, Shiho Aoki1,3,4, Hirohumi Uchiyama2,3, Koji Kawata2 , Yosuke Nakayama3,5, Yasuhiro Nikawa1,2, Kisato Kusano2 , Mitsuyasu Okabe2 , Tadaaki Miyazaki3,4,5*
1 Aureo Science Co., Ltd., Sapporo, Hokkaido, Japan, 2 Aureo Co., Ltd., Kimitsu, Chiba, Japan, 3 Department of Bioresources, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan, 4Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan, 5 Research Section of Probiotics Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan
Abstract
b-(1R3)-D-glucans with b-(1R6)-glycosidic linked branches produced by mushrooms, yeast and fungi are known to be an
immune activation agent, and are used in anti-cancer drugs or health-promoting foods. In this report, we demonstrate that
oral administration of Aureobasidium pullulans-cultured fluid (AP-CF) enriched with the b-(1R3),(1R6)-D-glucan exhibits
efficacy to protect mice infected with a lethal titer of the A/Puerto Rico/8/34 (PR8; H1N1) strain of influenza virus. The
survival rate of the mice significantly increased by AP-CF administration after sublethal infection of PR8 virus. The virus titer
in the mouse lung homogenates was significantly decreased by AP-CF administration. No significant difference in the mRNA
expression of inflammatory cytokines, and in the population of lymphocytes was observed in the lungs of mice
administered with AP-CF. Interestingly, expression level for the mRNA of virus sensors, RIG-I (retinoic acid-inducible gene-I)
and MDA5 (melanoma differentiation-associated protein 5) strongly increased at 5 hours after the stimulation of A.
pullulans-produced purified b-(1R3),(1R6)-D-glucan (AP-BG) in murine macrophage-derived RAW264.7 cells. Furthermore,
the replication of PR8 virus was significantly repressed by pre-treatment of AP-BG. These findings suggest the increased
expression of virus sensors is effective for the prevention of influenza by the inhibition of viral replication with the
administration of AP-CF.
Citation: Muramatsu D, Iwai A, Aoki S, Uchiyama H, Kawata K, et al. (2012) b-Glucan Derived from Aureobasidium pullulans Is Effective for the Prevention of
Influenza in Mice. PLoS ONE 7(7): e41399. doi:10.1371/journal.pone.0041399
Editor: Kevin Harrod, Lovelace Respiratory Research Institute, United States of America
Received January 5, 2012; Accepted June 21, 2012; Published July 23, 2012
Copyright: 2012 Muramatsu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was funded by by Aureo Co., Ltd., and Aureo-Science Co., Ltd. This work was supported, in part, by the Program of Founding Research
Centers for Emerging and Reemerging Infectious Diseases and Global COE Program Establishment of International Collaboration Centers for Zoonosis Control
from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. The funders had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript. No additional external funding was received for this study.
Competing Interests: Mr. Yasuhiro Nikawa and Dr. Mitsuyasu Okabe are employees of Aureo Co., Ltd., and Mr. Daisuke Muramatsu, Dr. Atsushi Iwai, Miss Shiho
Aoki, Mr. Hirohumi Uchiyama, Dr. Koji Kawata, and Mr. Yasuhiro Nikawa are employees of Aureo-Science Co., Ltd. The results presented in this manuscript are
patent pending in Japan (application number: 2009-234023). There are no other patents, products in development or marketed products to declare. This does not
alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials.
* E-mail: miyazaki@pop.med.hokudai.ac.jp
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