To understand the role of interferon (IFN)-γ gene (IFNG) single-nucleotide polymorphisms (SNPs) in the resistance to H5N1 highly pathogenic avian influenza (HPAI), we determined the SNPs, the log2-transformed specific antibody titers, and ex vivo recall antigen-specific IFN-γ production by peripheral blood mononuclear cells (PBMCs) in 62 red junglefowls (Gallus gallus) immunized twice with inactivated H5N1 HPAI vaccine. Consequently, 52 SNPs were detected in the amplified 1137-bp length covering the promoter region and all exons, with +2133A/T SNP in the coding DNA sequence that caused a missense mutation and was identified in G. gallus for the first time. For −316A/G SNP genotypes, the chi-squared test showed that the bird sample was in the Hardy–Weinberg equilibrium (P=0.369>0.05), and the least squares analysis revealed an increasing tendency in the antibody titers with G to A substitution so that a significant difference occurred between the AA genotype (8.031±0.247) and the GG genotype (6.571±0.528) (P=0.015<0.05, 95% confidence interval [CI]: 0.0004–0.0866), as basically consistent with the antigen-induced IFN-γ protein expression, which indicated possible association of the −316A/G SNP with a secondary humoral immune response to the HPAI vaccine in the bird population. These findings may help to improve genetic resistance using cross-breeding and enhance HPAI vaccine-induced immunity in chicken production.
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References
1.
AhmedKA, SaxenaVK, AraA, SinghKB, SundaresanNR, SaxenaM, RasoolTJ. 2007. Immune response to Newcastle disease virus in chicken lines divergently selected for cutaneous hypersensitivity. Int J Immunogenet, 34(6):445–455.
2.
BaumgarthN, KelsoA. 1996. In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue. J Virol, 70(7):4411–4418.
3.
BorrielloF, KrauterKS. 1990. Reactive site polymorphism in the murine protease inhibitor gene family is delineated using a modification of the PCR reaction (PCR+1). Nucleic Acids Res, 18(18):5481–5487.
4.
BotA, BotS, BonaCA. 1998. Protective role of gamma interferon during the recall response to influenza virus. J Virol, 72(8):6637–6645.
5.
ByleveldPM, PangGT, ClancyRL, RobertsDC. 1999. Fish oil feeding delays influenza virus clearance and impairs production of interferon-gamma and virus-specific immunoglobulin A in the lungs of mice. J Nutr, 129(2):328–335.
6.
CargneluttiDE, SanchezMA, AlvarezP, BoadoL, MattionN, ScodellerEA. 2013. Enhancement of Th1 immune responses to recombinant influenza nucleoprotein by Ribi adjuvant. New Microbiol, 36(2):145–151.
7.
CrawfordDC, NickersonDA. 2005. Definition and clinical importance of haplotypes. Annu Rev Med, 56:303–320.
8.
DesvauxS, MarxN, OngS, GaidetN, HuntM, ManuguerraJC, SornS, PeirisM, Van der WerfS, ReynesJM. 2009. Highly pathogenic avian influenza virus (H5N1) outbreak in captive wild birds and cats, Cambodia. Emerg Infect Dis, 15(3):475–478.
9.
DowningT, LynnDJ, ConnellS, LloydAT, BhuiyanAK, SilvaP, NaqviAN, SanfoR, SowRS, PodisiB, O'FarrellyC, HanotteO, BradleyDG. 2009. Contrasting evolution of diversity at two disease-associated chicken genes. Immunogenetics, 61(4):303–314.
10.
GeMQ, HoAW, TangY, WongKH, ChuaBY, GasserS, KemenyDM. 2012. NK cells regulate CD8+ T cell priming and dendritic cell migration during influenza A infection by IFN-γ and perforin-dependent mechanisms. J Immunol, 189(5):2099–2109.
11.
HaghighiHR, ReadLR, HaeryfarSM, BehboudiS, SharifS. 2009. Identification of a dual-specific T cell epitope of the hemagglutinin antigen of an h5 avian influenza virus in chickens. PLoS One, 4(11):e7772.
12.
HillaireML, van TrierumSE, BodewesR, van BaalenCA, van BinnendijkRS, KoopmansMP, FouchierRA, OsterhausAD, RimmelzwaanGF. 2011. Characterization of the human CD8+ T cell response following infection with 2009 pandemic influenza H1N1 virus. J Virol, 85(22):12057–12061.
13.
HuangS, HendriksW, AlthageA, HemmiS, BluethmannH, KamijoR, VilcekJ, ZinkernagelRM, AguetM. 1993. Immune response in mice that lack the interferon-gamma receptor. Science, 259(5102):1742–1745.
14.
KaiserP, HowellJ, FifeM, SadeyenJR, SalmonN, RothwellL, YoungJ, van DiemenP, StevensM, PohTY, JonesM, BarrowP, SwaggertyC, KogutM, SmithJ, BurtD. 2008. Integrated immunogenomics in the chicken: deciphering the immune response to identify disease resistance genes. Dev Biol (Basel), 132:57–66.
15.
KaiserP, WainHM, RothwellL. 1998. Structure of the chicken interferon-gamma gene, and comparison to mammalian homologues. Gene, 207(1):25–32.
16.
KarpalaAJ, BinghamJ, SchatKA, ChenLM, DonisRO, LowenthalJW, BeanAG. 2011. Highly pathogenic (H5N1) avian influenza induces an inflammatory T helper type 1 cytokine response in the chicken. J Interferon Cytokine Res, 31(4):393–400.
17.
KarupiahG, ChenJH, MahalingamS, NathanCF, MacMickingJD. 1998. Rapid interferon gamma-dependent clearance of influenza A virus and protection from consolidating pneumonitis in nitric oxide synthase 2-deficient mice. J Exp Med, 188(8):1541–1546.
18.
LambrechtB, GonzeM, MeulemansG, van den BergTP. 2004. Assessment of the cell-mediated immune response in chickens by detection of chicken interferon-γ in response to mitogen and recall Newcastle disease viral antigen stimulation. Avian Pathol, 33(3):343–350.
19.
LamontSJ. 2002. Candidate genes for immune response and disease resistance in chickens. Available at www.poultryscience.org/docs/pba/1952–2003/2002/2002%20Lamont.pdf (accessed 24. 12.2014).
20.
LiuB, MoriI, HossainMJ, DongL, ChenZ, KimuraY. 2003. Local immune responses to influenza virus infection in mice with a targeted disruption of perforin gene. Microb Pathog, 34(4):161–167.
21.
LühkenG, GaulyM, KaufmannF, ErhardtG. 2011. Association study in naturally infected helminth layers shows evidence for influence of interferon-gamma gene variants on Ascaridia galli worm burden. Vet Res, 42:84.
22.
McNallyB, YeF, WilletteM, FlañoE. 2013. Local blockade of epithelial PDL-1 in the airways enhances T cell function and viral clearance during influenza virus infection. J Virol, 87(23):12916–12924.
23.
MohrE, CunninghamAF, ToellnerKM, BobatS, CoughlanRE, BirdRA, MacLennanIC, SerreK. 2010. IFN-γ produced by CD8 T cells induces T-bet-dependent and -independent class switching in B cells in responses to alum-precipitated protein vaccine. Proc Natl Acad Sci U S A, 107(40):17292–17297.
24.
NayakB, KumarS, DiNapoliJM, PalduraiA, PerezDR, CollinsPL, SamalSK. 2010. Contributions of the avian influenza virus HA, NA, and M2 surface proteins to the induction of neutralizing antibodies and protective immunity. J Virol, 84(5):2408–2420.
25.
PrabhuN, HoAW, WongKH, HutchinsonPE, ChuaYL, KandasamyM, LeeDC, SivasankarB, KemenyDM. 2013. Gamma interferon regulates contraction of the influenza virus-specific CD8 T cell response and limits the size of the memory population. J Virol, 87(23):12510–12522.
26.
ReemersSSN, van HaarlemDA, SijtsAJAM, VerveldeL, JansenCA. 2012. Identification of novel avian influenza virus derived CD8+ T-Cell epitopes. PLoS One, 7(2):e31953.
27.
SambharaS, SwitzerI, KurichhA, MirandaR, UrbanczykL, JamesO, UnderdownB, KleinM, BurtD. 1998. Enhanced antibody and cytokine responses to influenza viral antigens in perforin-deficient mice. Cell Immunol, 187(1):13–18.
28.
SarawarSR, SangsterM, CoffmanRL, DohertyPC. 1994. Administration of anti-IFN-gamma antibody to beta 2-microglobulin-deficient mice delays influenza virus clearance but does not switch the response to a T helper cell 2 phenotype. J Immunol, 153(3):1246–1253.
29.
SawaiH, KimHL, KunoK, SuzukiS, GotohH, TakadaM, TakahataN, SattaY, AkishinonomiyaF. 2010. The origin and genetic variation of domestic chickens with special reference to junglefowls Gallus g. gallus and G. varius. PLoS One, 5(5):e10639.
30.
SchroderK, HertzogPJ, RavasiT, HumeDA. 2004. Interferon-γ: an overview of signals, mechanisms and functions. J Leukoc Biol, 75(2):163–189.
31.
SeoSH, PeirisM, WebsterRG. 2002. Protective cross-reactive cellular immunity to lethal A/Goose/Guangdong/1/96-Like H5N1 influenza virus is correlated with the proportion of pulmonary CD8+ T cells expressing gamma interferon. J Virol, 76(10):4886–4890.
32.
SinghS, PeiJ, CollissonEW. 2014. Viral specific CD8+T lymphocyte immunity provides protection against heterotypic stains of avian influenza viruses and avian coronaviruses. Int Trends Immun, 2(1):36–46.
33.
SinghS, ToroH, TangDC, BrilesWE, YatesLM, KopulosRT, CollissonEW. 2010. Non-replicating adenovirus vectors expressing avian influenza virus hemagglutinin and nucleocapsid proteins induce chicken specific effector, memory and effector memory CD8(+) T lymphocytes. Virology, 405(1):62–69.
34.
UnoY, UsuiT, SodaK, FujimotoY, TakeuchiT, ItoH, ItoT, YamaguchiT. 2013. The pathogenicity and host immune response associated with H5N1 highly pathogenic avian influenza virusin quail. J Vet Med Sci, 75(4):451–457.
35.
VerveldeL, MatthijsMG, van HaarlemDA, de WitJJ, JansenCA. 2013. Rapid NK-cell activation in chicken after infection with infectious bronchitis virus M41. Vet Immunol Immunopathol, 151(3–4):337–341.
36.
WeissID, WaldO, WaldH, BeiderK, AbrahamM, GalunE, NaglerA, PeledA. 2010. IFN-gamma treatment at early stages of influenza virus infection protects mice from death in a NK cell-dependent manner. J Interferon Cytokine Res, 30(6):439–449.
37.
YeX, AvendanoS, DekkersJC, LamontSJ. 2006. Association of twelve immune-related genes with performance of three broilers lines in two different hygiene environments. Poult Sci, 85(9):1555–1569.
38.
ZhouH, BuitenhuisAJ, WeigendS, LamountSJ. 2001. Candidate gene promoter polymorphisms and antibody response kinetics in chickens: interferon-gamma, interleukin-2, and immunoglobulin light chain. Poult Sci, 80(12):1679–1689.
39.
ZhouH, LillehojHS, LamontSJ. 2002. Associations of interferon-gamma genotype and protein level with antibody response kinetics in chickens. Avian Dis, 46(4):869–876.
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