Abstract
The highly pathogenic avian influenza virus H5N1 is known to induce high level of tumor necrosis factor α (TNF-α) from primary macrophages. However, it is still unclear whether current H5N1 strains also induce high TNF-α 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-α that are not necessarily higher than those induced by seasonal influenza viruses. The result suggests that hyper-induction of TNF-α 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-α induction by using reverse genetics. While NS conferred some variation in TNF-α induction when incorporated into an H1N1 virus genetic background, it did not affect TNF-α induction in an H5N1 virus genetic background, suggesting that other viral genes are involved.
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Acknowledgments
This project was supported by a research grant from the Thailand Research Fund (BRG5180008). The Mahidol University–University of Tokyo collaboration was supported by the JSPS (Japan Society for the Promotion of Science). Sirawat Srichatraphimuk and Yuwarat Monteerarat were supported by the Mahidol Medical Scholar Program. Pilaipan Puthavathana was supported by a Senior Research Scholar grant from the Thailand Research Fund. This work was also supported by National Institute of Allergy and Infectious Diseases Public Health Service research grants, by an NIAID-funded Center for Research on Influenza Pathogenesis (CRIP, HHSN266200700010C), by a Grant-in-Aid for Specially Promoted Research, by a contract research fund for the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases from the Ministry of Education, Culture, Sports, Science, and Technology, by grants-in-aid from the Ministry of Health and by ERATO (Japan Science and Technology Agency). H5N1 viral isolates from Thailand were kindly provided through collaboration with the Department of Medical Sciences, Bureau of Epidemiology and Faculty of Veterinary Science of Mahidol University, partly under a US CDC-funded collaborative project “Avian Influenza Surveillance in Thailand-Studies at Human–Animal Interface”. The viral strain collection was facilitated by the Thailand Avian Influenza Monitoring Network (TAIM Net) established by the National Center for Genetic Engineering and Biotechnology.
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Monteerarat, Y., Sakabe, S., Ngamurulert, S. et al. Induction of TNF-α in human macrophages by avian and human influenza viruses. Arch Virol 155, 1273–1279 (2010). https://doi.org/10.1007/s00705-010-0716-y
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DOI: https://doi.org/10.1007/s00705-010-0716-y