Induction of TNF-α in human macrophages by avian and human influenza viruses

Abstract

The highly pathogenic avian influenza virus H5N1 is known to induce high level of tumor necrosis factor alpha (TNF-alpha) from primary macrophages. However, it is still unclear whether current H5N1 strains also induce high TNF-alpha 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-alpha that are not necessarily higher than those induced by seasonal influenza viruses. The result suggests that hyper-induction of TNF-alpha 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-alpha induction by using reverse genetics. While NS conferred some variation in TNF-alpha induction when incorporated into an H1N1 virus genetic background, it did not affect TNF-alpha induction in an H5N1 virus genetic background, suggesting that other viral genes are involved.

Editorial: Macrophage heterogeneity and responses to influenza virus infection

“…The strain of H5N1 virus A/Thailand/KAN-1/2004, which they use, has also been found by others to be a poor cytokine inducer [10]. The cytokine induction phenotype of HPAI H7N7 has not been investigated in detail by others, but our own unpublished data suggest that H7N7 viruses are not potent inducers of proinflammatory cytokines, which is in agreement with the findings of Friesenhagen and colleagues [2].…”

“…Although HPAI H5N1 viruses in general appear to be more potent inducers of proinflammatory cytokines compared with seasonal influenza viruses in MDMs, there is variation between different H5N1 virus strains, and some H5N1 strains induce cytokines to a similar extent of seasonal influenza viruses [8,10]. Furthermore, there is variation between donors in the intensity of the cytokine/chemokine response.…”

Influenza virus replication in macrophages: balancing protection and pathogenesis

“…The H5N1 viruses HK/483 and HK/486 both induce high levels of TNF-a in human MDMs relative to seasonal viruses, despite the fact that HK/486 does not replicate in human MDMs [32,52]. Moreover, the induction of TNF-a in WSN-infected human MDMs is not elevated when compared to infection with seasonal H1N1 or H3N2 viruses [60]. Taken together, these findings indicate that excessive cytokine production does not always correlate with productive virus replication in macrophages.…”

Influenza-Induced Innate Immunity: Regulators of Viral Replication, Respiratory Tract Pathology & Adaptive Immunity

“…Importantly, not all H5N1 viruses are created equal. Different H5N1 clades induce quantitative differences in cytokine (IL-12, IL-16, IL-9 and TNF-α) and chemokine expression [43,44,64]. Thus, there are high and low cytokine-inducing clades even within the same pathogenic influenza strain.…”