Abstract
BackgroundThe mechanisms of disease severity caused by H5N1 influenza virus infection remain somewhat unclear. Studies have indicated that a high viral load and an associated hyper inflammatory immune response are influential during the onset of infection. This dysregulated inflammatory response with increased levels of free radicals, such as nitric oxide (NO), appears likely to contribute to disease severity. However, enzymes of the nitric oxide synthase (NOS) family such as the inducible form of NOS (iNOS) generate NO, which serves as a potent anti-viral molecule to combat infection in combination with acute phase proteins and cytokines. Nevertheless, excessive production of iNOS and subsequent high levels of NO during H5N1 infection may have negative effects, acting with other damaging oxidants to promote excessive inflammation or induce apoptosis.Methodology/Principal FindingsThere are dramatic differences in the severity of disease between chickens and ducks following H5N1 influenza infection. Chickens show a high level of mortality and associated pathology, whilst ducks show relatively minor symptoms. It is not clear how this varying pathogenicty comes about, although it has been suggested that an overactive inflammatory immune response to infection in the chicken, compared to the duck response, may be to blame for the disparity in observed pathology. In this study, we identify and investigate iNOS gene expression in ducks and chickens during H5N1 influenza infection. Infected chickens show a marked increase in iNOS expression in a wide range of organs. Contrastingly, infected duck tissues have lower levels of tissue related iNOS expression.Conclusions/SignificanceThe differences in iNOS expression levels observed between chickens and ducks during H5N1 avian influenza infection may be important in the inflammatory response that contributes to the pathology. Understanding the regulation of iNOS expression and its role during H5N1 influenza infection may provide insights for the development of new therapeutic strategies in the treatment of avian influenza infection.
Highlights
H5N1 influenza virus strains have been prevalent and highly pathogenic in gallinaceous birds, chickens, causing acute systemic disease [1,2,3]
Understanding the role that nitric oxide (NO) and inducible form of NOS (iNOS) play during H5N1 infection in chickens and ducks [1,4,34] may provide insights into the underlying mechanisms and differences observed in disease severity
To investigate this we identified the presence of the iNOS gene in ducks and confirmed that duck iNOS (dkiNOS) acts in a similar fashion to its chicken counterpart [27]
Summary
H5N1 influenza virus strains have been prevalent and highly pathogenic in gallinaceous birds, chickens, causing acute systemic disease [1,2,3]. Viral replication may be associated with an increased proinflammatory response [9,10,11], as chickens exhibit widespread viremia and an associated increase in cytokines, leading to inflammation This suggests that H5N1 may be a potent inducer of proinflammatory cytokines, chemokines and free radicals in chickens [9,11,12,13]. Studies have indicated that a high viral load and an associated hyper inflammatory immune response are influential during the onset of infection. This dysregulated inflammatory response with increased levels of free radicals, such as nitric oxide (NO), appears likely to contribute to disease severity. Excessive production of iNOS and subsequent high levels of NO during H5N1 infection may have negative effects, acting with other damaging oxidants to promote excessive inflammation or induce apoptosis
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