Differential responses of innate immunity triggered by different subtypes of influenza a viruses in human and avian hosts

Abstract

BackgroundInnate immunity provides first line of defense against viral infections. The interactions between hosts and influenza A virus and the response of host innate immunity to viral infection are critical determinants for the pathogenicity or virulence of influenza A viruses. This study was designed to investigate global changes of gene expression and detailed responses of innate immune systems in human and avian hosts during the course of infection with various subtypes of influenza A viruses, using collected and self-generated transcriptome sequencing data from human bronchial epithelial (HBE), human tracheobronchial epithelial (HTBE), and A549 cells infected with influenza A virus subtypes, namely H1N1, H3N2, H5N1 HALo mutant, and H7N9, and from ileum and lung of chicken and quail infected with H5N1, or H5N2.ResultsWe examined the induction of various cytokines and chemokines in human hosts infected with different subtypes of influenza A viruses. Type I and III interferons were found to be differentially induced with each subtype. H3N2 caused abrupt and the strongest response of IFN-β and IFN-λ, followed by H1N1 (though much weaker), whereas H5N1 HALo mutant and H7N9 induced very minor change in expression of type I and III interferons. Similarly, differential responses of other innate immunity-related genes were observed, including TMEM173, MX1, OASL, IFI6, IFITs, IFITMs, and various chemokine genes like CCL5, CX3CL1, and chemokine (C-X-C motif) ligands, SOCS (suppressors of cytokine signaling) genes. Third, the replication kinetics of H1N1, H3N2, H5N1 HALo mutant and H7N9 subtypes were analyzed, H5N1 HALo mutant was found to have the highest viral replication rate, followed by H3N2, and H1N1, while H7N9 had a rate similar to that of H1N1 or H3N2 though in different host cell type.ConclusionOur study illustrated the differential responses of innate immunity to infections of different subtypes of influenza A viruses. We found the influenza viruses which induced stronger innate immune responses replicate slower than those induces weaker innate immune responses. Our study provides important insight into links between the differential innate immune responses from hosts and the pathogenicity/ virulence of different subtypes of influenza A viruses.Electronic supplementary materialThe online version of this article (10.1186/s12920-017-0304-z) contains supplementary material, which is available to authorized users.

The protective and pathogenic roles of CXCL17 in human health and disease: Potential in respiratory medicine

“…As such, the possibility for a potential role for this chemokine in respiratory infections is warranted. Indeed, CXCL17 along with other chemokines such as CXCL1, 8, 10, 11 and 16 has been found to be highly expressed in human bronchial epithelial, human tracheobronchial epithelial and A549 cells infected with influenza A/H3N2 virus but reduced in these cells infected with A/H5N1 and A/H7N9 strains [87]. Avian influenza A/H5N1 and A/H7N9 strains are more virulent due to acquired genetic properties contributing to a faster replication rate and rate of infection compared to seasonal influenza A/ H1N1 and A/H3N2 strains [88,89].…”

CXCL17 is a Prognostic Biomarker That Distinguishes Severe Pandemic InfluenzaA(H1N1) from COVID-19

“…Indeed, previous research showed that the infection of human bronchial epithelial cells, human tracheobronchial epithelial cells, and human alveolar A549 cells with seasonal in uenza A(H3N2) virus, promotes robust upregulation of CXCL17. However, the infection with more virulent A(H5N1) and A(H7N9) in uenza virus subtypes induces minor changes in the expression of CXCL17 [18]. Similarly, in a yet unpublished experiment available from the In uenza Research Database (IRD), the infection of 2B-4cells/sorted Calu-3 cells with a wild type strain of the 2002-2003 SARS-CoV (icSARS CoV) did not stimulate strong expression of CXCL17 [19].…”

The Drivers of Pathology in Zoonotic Avian Influenza: The Interplay Between Host and Pathogen

“…The role of IFITMs against AI viruses in avian species has not been clearly defined, though a study by Smith and colleagues has shown that chicken IFITM3 (which is “human IFITM1-like”) similarly restricts H5 and H7 expressing viruses ( 143 ). However, when chickens were infected with H5N1, expression of IFITM molecules was not highly upregulated compared to other human-infecting seasonal strains such as H1N1, with IFITMs showing the weakest inhibiting effect against H7N9 ( 144 ). Hence, IFITM expression in chickens appears to be limited and does not vary greatly whether the virus is of low or high pathogenicity.…”