Abstract

BackgroundInfluenza A virus (IAV) is a major public health concern, being responsible for the death of approximately half a million people each year. Zoonotic transmissions of the virus from swine and avian origin have occurred in the past, and can potentially lead to the emgergence of new IAV stains in future pandemics. Pulmonary macrophages have been implicated in disease severity in the lower airway, and understanding the host response of macrophages infected with avian influenza viruses should provide new therapeutic strategies.ResultsWe used a systems-based approach to investigate the transcriptome response of primary murine lung macrophages (PMФ) infected with the mouse-adapted H1N1/WSN virus and low pathogenic avian influenza (LPAI) viruses H5N2 and H5N3. The results showed that the LPAI viruses H5N2 and H5N3 can infect PMФ with similar efficiency to the H1N1/WSN virus. While all viruses induced antiviral responses, the H5N3 virus infection resulted in higher expression levels of cytokines and chemokines associated with inflammatory responses.ConclusionsThe LPAI H5N2 and H5N3 viruses are able to infect murine lung macrophages. However, the H5N3 virus was associated with increased expression of pro-inflammatory mediators. Although the H5N3 virus it is capable of inducing high levels of cytokines that are associated with inflammation, this property is distinct from its inability to efficiently replicate in a mammalian host.

Highlights

  • Influenza A virus (IAV) is a major public health concern, being responsible for the death of approximately half a million people each year

  • We have previously described the biological properties of several low pathogenic avian influenza (LPAI) viruses that were isolated from imported live poultry during routine surveillance, which included H5N2, H5N3 and H9N2 viruses [30, 31]

  • We have extended our previous findings on these LPAI viruses and have applied a system-based approach to investigate the host response to these viruses in murine lung macrophages

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Summary

Introduction

Influenza A virus (IAV) is a major public health concern, being responsible for the death of approximately half a million people each year. Pulmonary macrophages have been implicated in disease severity in the lower airway, and understanding the host response of macrophages infected with avian influenza viruses should provide new therapeutic strategies. Influenza A virus (IAV) represents one of the most important biological threats to human health and the global economy [1,2,3]. It causes yearly seasonal epidemics and periodic pandemics [4]. Seasonal influenza is estimated to be the cause up to 5 million severe cases and approximately 500,000 deaths each year. Based on disease severity in birds, avian IAV can be classified as either being low

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