Characterization of Host Responses against a Recombinant Fowlpox Virus-Vectored Vaccine Expressing the Hemagglutinin Antigen of an Avian Influenza Virus

ABSTRACT There currently are commercial fowlpox virus (FPV)-vectored vaccines for use in chickens, including TROVAC-AIV H5, which expresses the hemagglutinin (HA) antigen of an avian influenza virus and can confer immunity against avian influenza in chickens. Despite the use of recombinant FPV (rFPV) for vaccine delivery, very little is known about the immune responses generated by these viruses in chickens. The present study was designed to investigate host responses to rFPV in vivo and in vitro. In cultured cells infected with TROVAC-AIV H5, there was an early increase in the expression of type I interferons (IFN), Toll-like receptors 3 and 7 (TLR3 and TLR7, respectively), TRIF, and MyD88, which was followed by a decrease in the expression of these genes at later time points. There also was an increase in the expression of interleukin-1β (IL-1β), IL-8, and beta-defensin genes at early time points postinfection. In chickens immunized with TROVAC-AIV H5, there was higher expression of IFN-γ and IL-10 at day 5 postvaccination in spleen of vaccinated birds than in that of control birds. We further investigated the ability of the vaccine to induce immune responses against the HA antigen and discovered that there was a cell-mediated response elicited in vaccinated chickens against this antigen. The findings of this study demonstrate that FPV-vectored vaccines can elicit a repertoire of responses marked by the early expression of TLRs, type I interferons, and proinflammatory cytokines, as well as cytokines associated with adaptive immune responses. This study provides a platform for designing future generations of rFPV-vectored vaccines.

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Differential cellular immune responses between chickens and ducks to H9N2 avian influenza virus infection

Veterinary Immunology and Immunopathology ◽

10.1016/j.vetimm.2012.09.010 ◽

2012 ◽

Vol 150 (3-4) ◽

pp. 169-180 ◽

Cited By ~ 14

Author(s):

Zhenyu Huang ◽

Dong Fang ◽

Peng Lv ◽

Xuebing Bian ◽

Xizhen Ruan ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Avian Influenza ◽

Immune Responses ◽

Avian Influenza Virus ◽

Influenza Virus Infection ◽

H9n2 Avian Influenza Virus ◽

Cellular Immune Responses ◽

Cellular Immune

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Knockout of IRF7 Highlights its Modulator Function of Host Response Against Avian Influenza Virus and the Involvement of MAPK and TOR Signaling Pathways in Chicken

Genes ◽

10.3390/genes11040385 ◽

2020 ◽

Vol 11 (4) ◽

pp. 385

Author(s):

Tae Hyun Kim ◽

Colin Kern ◽

Huaijun Zhou

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Signaling Pathways ◽

Cell Lines ◽

Host Response ◽

Antiviral Response ◽

Influenza Viruses ◽

Interferon Response ◽

Type I

Interferon regulatory factor 7 (IRF7) is known as the master transcription factor of the type I interferon response in mammalian species along with IRF3. Yet birds only have IRF7, while they are missing IRF3, with a smaller repertoire of immune-related genes, which leads to a distinctive immune response in chickens compared to in mammals. In order to understand the functional role of IRF7 in the regulation of the antiviral response against avian influenza virus in chickens, we generated IRF7-/- chicken embryonic fibroblast (DF-1) cell lines and respective controls (IRF7wt) by utilizing the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) system. IRF7 knockout resulted in increased viral titers of low pathogenic avian influenza viruses. Further RNA-sequencing performed on H6N2-infected IRF7-/- and IRF7wt cell lines revealed that the deletion of IRF7 resulted in the significant down-regulation of antiviral effectors and the differential expression of genes in the MAPK (mitogen-activated protein kinase) and mTOR (mechanistic target of rapamycin) signaling pathways. Dynamic gene expression profiling of the host response between the wildtype and IRF7 knockout revealed potential signaling pathways involving AP1 (activator protein 1), NF-κB (nuclear factor kappa B) and inflammatory cytokines that may complement chicken IRF7. Our findings in this study provide novel insights that have not been reported previously, and lay a solid foundation for enhancing our understanding of the host antiviral response against the avian influenza virus in chickens.

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Corrigendum to “Recombinant fowlpox virus vector-based vaccine completely protects chickens from H5N1 avian influenza virus” [Antiviral Res. 81 (3) (2009) 234–238]

Antiviral Research ◽

10.1016/j.antiviral.2009.07.019 ◽

2009 ◽

Vol 84 (1) ◽

pp. 98-99 ◽

Cited By ~ 1

Author(s):

Chuanling Qiao ◽

Yongping Jiang ◽

Guobin Tian ◽

XiurongWang ◽

Chengjun Li ◽

...

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Virus Vector ◽

Fowlpox Virus ◽

H5n1 Avian Influenza Virus ◽

H5n1 Avian Influenza ◽

Recombinant Fowlpox Virus

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Type I Interferons Mediate the Innate Cytokine Response to Recombinant Fowlpox Virus but Not the Induction of Plasmacytoid Dendritic Cell-Dependent Adaptive Immunity

Journal of Virology ◽

10.1128/jvi.02618-09 ◽

2010 ◽

Vol 84 (13) ◽

pp. 6549-6563 ◽

Cited By ~ 7

Author(s):

Erin L. Lousberg ◽

Cara K. Fraser ◽

Michael G. Tovey ◽

Kerrilyn R. Diener ◽

John D. Hayball

Keyword(s):

Immune Responses ◽

Plasmacytoid Dendritic Cell ◽

Type I Interferons ◽

Interleukin 12 ◽

Type I ◽

Adaptive Immune Responses ◽

Fowlpox Virus ◽

Adaptive Immune ◽

Type I Ifns

ABSTRACT Type I interferons (IFNs) are considered to be important mediators of innate immunity due to their inherent antiviral activity, ability to drive the transcription of a number of genes involved in viral clearance, and their role in the initiation of innate and adaptive immune responses. Due to the central role of type I IFNs, we sought to determine their importance in the generation of immunity to a recombinant vaccine vector fowlpox virus (FPV). In analyzing the role of type I IFNs in immunity to FPV, we show that they are critical to the secretion of a number of innate and proinflammatory cytokines, including type I IFNs themselves as well as interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-α), IL-6, and IL-1β, and that deficiency leads to enhanced virus-mediated antigen expression. Interestingly, however, type I IFNs were not required for adaptive immune responses to recombinant FPV even though plasmacytoid dendritic cells (pDCs), the primary producers of type I IFNs, have been shown to be requisite for this to occur. Furthermore, we provide evidence that the importance of pDCs may lie in their ability to capture and present virally derived antigen to T cells rather than in their capacity as professional type I IFN-producing cells.

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