ORIGINAL ARTICLE Induction of TNF-a in human macrophages by avian and human influenza viruses Yuwarat Monteerarat • Saori Sakabe • Somying Ngamurulert • Sirawat Srichatraphimuk • Wasana Jiamtom • Kridsada Chaichuen • Arunee Thitithanyanont • Parichart Permpikul • Taweesak Songserm • Pilaipan Puthavathana • Chairul A. Nidom • Le Quynh Mai • Kiyoko Iwatsuki-Horimoto • Yoshihiro Kawaoka • Prasert Auewarakul Received: 8 March 2010 / Accepted: 25 May 2010 / Published online: 9 June 2010 Ó Springer-Verlag 2010 Abstract The highly pathogenic avian influenza virus H5N1 is known to induce high level of tumor necrosis factor a (TNF-a) from primary macrophages. However, it is still unclear whether current H5N1 strains also induce high TNF-a production, as most of the data were derived from extinct clade 0 H5N1 strain. Here, we show that current clade 1 and 2 H5N1 strains induce variable levels of TNF-a that are not necessarily higher than those induced by seasonal influenza viruses. The result suggests that hyper-induction of TNF-a in human macrophages is not always associated with a highly pathogenic phenotype. We further tested the contribution of the NS gene segment from H5N1 isolates to TNF-a induction by using reverse genetics. While NS conferred some variation in TNF-a induction when incorporated into an H1N1 virus genetic background, it did not affect TNF-a induction in an H5N1 virus genetic background, suggesting that other viral genes are involved. Introduction Highly pathogenic H5N1 avian influenza viruses can be transmitted directly from avian species to humans. Their virulence is extremely high, producing 100% mortality in Y. Monteerarat Á S. Ngamurulert Á S. Srichatraphimuk Á W. Jiamtom Á P. Puthavathana Á P. Auewarakul (&) Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand e-mail: sipaw@mahidol.ac.th S. Sakabe Á K. Iwatsuki-Horimoto Á Y. Kawaoka Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan K. Chaichuen Faculty of Veterinary Science, Mahidol University, Nakhon Pathom 73170, Thailand A. Thitithanyanont Faculty of Science, Mahidol University, Bangkok 10400, Thailand P. Permpikul Department of Transfusion Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand T. Songserm Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10903, Thailand C. A. Nidom Avian Influenza Laboratory, Tropical Disease Centre, Airlannga University, Surabaya 60286, Indonesia L. Q. Mai National Institute of Hygiene and Epidemiology, Hanoi 10000, Vietnam Y. Kawaoka International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan Y. Kawaoka Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA Y. Kawaoka ERATO Infection-Induced Host Responses Project, Saitama 332-0012, Japan 123 Arch Virol (2010) 155:1273–1279 DOI 10.1007/s00705-010-0716-y