This study demonstrates the capacity of HM-γ-PGA treatment to significantly protect murine macrophage cells (RAW 264.7 cells) against NDV infection. Such protection can be explained by the induction of antiviral state of HM-γ-PGA in RAW 264.7 cells via TLR4-mediated IRF-3, IRF-7, IFN-β, and IFN-related gene induction as shown in time-dependent changes in mRNA expression confirmed by polymerase chain reaction (PCR). Moreover, the present research also showed that HM-γ-PGA can induce proinflammatory cytokine secretion in RAW 264.7 as measured by enzyme-linked immunosorbent assay (ELISA). Therefore, our findings suggest that HM-γ-PGA can be a potential antiviral substance that can inhibit NDV infection through its stimulation of antiviral state on RAW 264.7 cells. These results have been consistent with the previous studies showing that HM-γ-PGA can protect RAW 264.7 cells and mice against influenza infection. However, it should be noted that although murine macrophage cells are susceptible to NDV, they are not the natural host cells of the virus; thus further in vivo and in vitro studies involving chicken and chicken immune cells are needed to fully assess the efficacy and applicability of HM-γ-PGA in the poultry industry. 1. Introduction Newcastle disease virus (NDV) is a member of the Paramyxoviridae family under the genus Avulavirus [1, 2] and is currently designated as avian paramyxovirus virus serotype 1 (APMV-1) [3]. According to the Office International des Epizooties (OIE) in 2009, NDV strains can be classified into five pathotypes according to the clinical signs shown by the affected chickens, namely, viscerotropic velogenic (high mortality and hemorrhagic intestinal lesions), neurotropic velogenic (high mortality, respiratory, and nervous signs), mesogenic (low mortality, respiratory signs with occasional nervous signs), lentogenic (subclinical or mild infection), and asymptomatic enteric (subclinical enteric infection) ones [4]. Newcastle disease remains prevalent worldwide, though a number of live and inactivated NDV vaccines are available to control the disease [5, 6]. However, the currently available commercial vaccines have their limitations and one of them is the absence of genetic markers for serological differentiation between vaccinated and naturally infected birds. There are also reports suggesting that the types of NDV strains that have been identified circulating in poultry already showed major antigenic drift. Thus, there is a need for better NDV vaccines which can solve such problems, wherein viral vector vaccines prove to be a
References
[1]
M. A. Mayo, “Virus taxonomy,” Archives of Virology, vol. 147, pp. 1071–1076, 2002.
[2]
M. A. Mayo, “A summary of taxonomic changes recently approved by ICTV,” Archives of Virology, vol. 147, no. 8, pp. 1655–1663, 2002.
[3]
D. J. Alexander, “Newcastle disease and other avian paramyxoviruses,” Revue Scientifique et Technique, vol. 19, no. 2, pp. 443–462, 2000.
[4]
Office International des Epizooties, “Manual of Diagnostic Tests and Vacc ines for Terrestrial Animals,” 2012, http://web.oie.int/eng/normes/MMANUAL/A_Index.htm.
[5]
B. S. Seal, D. J. King, and H. S. Sellers, “The avian response to Newcastle disease virus,” Developmental and Comparative Immunology, vol. 24, no. 2-3, pp. 257–268, 2000.
[6]
Y.-J. Lee, H.-W. Sung, J.-G. Choi et al., “Protection of chickens from Newcastle disease with a recombinant baculovirus subunit vaccine expressing the fusion and hemagglutinin-neuraminidase proteins,” Journal of Veterinary Science, vol. 9, no. 3, pp. 301–308, 2008.
[7]
S. Kumar, B. Nayak, P. L. Collins, and S. K. Samal, “Evaluation of the newcastle disease virus f and hn proteins in protective immunity by using a recombinant avian paramyxovirus type 3 vector in chickens,” Journal of Virology, vol. 85, no. 13, pp. 6521–6534, 2011.
[8]
K. Yamanouchi, T. Barrett, and C. Ka, “New approaches to the development of virus vaccines for veterinary use,” Revue scientifique et technique, vol. 17, no. 3, pp. 641–653, 1998.
[9]
D. J. Alexander, “Newcastle disease,” British Poultry Science, vol. 42, no. 1, pp. 5–22, 2001.
[10]
S.-R. Bae, C. Park, J.-C. Choi, H. Poo, C.-J. Kim, and M.-H. Sung, “Effects of ultra high molecular weight poly-γ-glutamic acid from Bacillus subtilis (chungkookjang) on corneal wound healing,” Journal of Microbiology and Biotechnology, vol. 20, no. 4, pp. 803–808, 2010.
[11]
M.-H. Sung, C. Park, C.-J. Kim, H. Poo, K. Soda, and M. Ashiuchi, “Natural and edible biopolymer poly-γ-glutamic acid: synthesis, production, and applications,” Chemical Record, vol. 5, no. 6, pp. 352–366, 2005.
[12]
H. Poo, C. Park, M.-S. Kwak et al., “New biological functions and applications of high-molecular-mass poly-γ-glutamic acid,” Chemistry and Biodiversity, vol. 7, no. 6, pp. 1555–1562, 2010.
[13]
H.-J. Moon, J.-S. Lee, Y.-K. Choi, et al., “Induction of type I interferon by high-molecular poly-γ-glutamate protects B6.A2G-Mx1 mice against influenza A virus,” Antiviral Research, vol. 94, no. 1, pp. 98–102, 2012.
[14]
T.-Y. Lee, Y.-H. Kim, S.-W. Yoon et al., “Oral administration of poly-gamma-glutamate induces TLR4- and dendritic cell-dependent antitumor effect,” Cancer Immunology, Immunotherapy, vol. 58, no. 11, pp. 1781–1794, 2009.
[15]
T. Yoshikawa, N. Okada, A. Oda et al., “Nanoparticles built by self-assembly of amphiphilic γ-PGA can deliver antigens to antigen-presenting cells with high efficiency: a new tumor-vaccine carrier for eliciting effector T cells,” Vaccine, vol. 26, no. 10, pp. 1303–1313, 2008.
[16]
W. K. Tae, Y. L. Tae, C. B. Hyun et al., “Oral administration of high molecular mass poly-γ-glutamate induces NK cell-mediated antitumor immunity,” The Journal of Immunology, vol. 179, no. 2, pp. 775–780, 2007.
[17]
C. Puig-Saus, A. Gros, R. Alemany, and M. Cascalló, “Adenovirus i-leader truncation bioselected against cancer-associated fibroblasts to overcome tumor stromal barriers,” Molecular Therapy, vol. 20, no. 1, pp. 54–62, 2012.
[18]
S. M. Shin, J. H. Kwon, S. Lee, et al., “Immunostimulatory effects of Cordyceps militaris on macrophages through enhanced production of cytokines via the activation of NFκB,” Immune Network, vol. 10, no. 2, pp. 55–63, 2010.
[19]
M. G. Wise, D. L. Suarez, B. S. Seal et al., “Development of a real-time reverse-transcription PCR for detection of Newcastle disease virus RNA in clinical samples,” Journal of Clinical Microbiology, vol. 42, no. 1, pp. 329–338, 2004.
[20]
J. R. Reed, R. P. Leon, M. K. Hall, and K. L. Schwertfeger, “Interleukin-1beta and fibroblast growth factor receptor 1 cooperate to induce cyclooxygenase-2 during early mammary tumourigenesis,” Breast Cancer Research, vol. 11, no. 2, article R21, 2009.
[21]
H. Wilden, P. Fournier, R. Zawatzky, and V. Schirrmacher, “Expression of RIG-I, IRF3, IFN-β and IRF7 determines resistance or susceptibility of cells to infection by Newcastle Disease Virus,” International Journal of Oncology, vol. 34, no. 4, pp. 971–982, 2009.
[22]
T. L. Wadsworth and D. R. Koop, “Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages,” Biochemical Pharmacology, vol. 57, no. 8, pp. 941–949, 1999.
[23]
K. von Maltzan and S. B. Pruett, “ELISA assays and alcohol: Increasing carbon chain length can interfere with detection of cytokines,” Alcohol, vol. 45, no. 1, pp. 1–9, 2011.
[24]
E. M. P？lsson-McDermott and L. A. J. O'Neill, “Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4,” Immunology, vol. 113, no. 2, pp. 153–162, 2004.
[25]
M. Yamamoto, S. Sato, H. Hemmi et al., “TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway,” Nature Immunology, vol. 4, no. 11, pp. 1144–1150, 2003.
[26]
A. Marijke Keestra and J. P. M. van Putten, “Unique properties of the chicken TLR4/MD-2 complex: selective lipopolysaccharide activation of the MyD88-dependent pathway,” The Journal of Immunology, vol. 181, no. 6, pp. 4354–4362, 2008.
[27]
H. Wilden, V. Schirrmacher, and P. Fournier, “Important role of interferon regulatory factor (IRF)-3 in the interferon response of mouse macrophages upon infection by Newcastle disease virus,” International Journal of Oncology, vol. 39, no. 2, pp. 493–504, 2011.
[28]
D. J. Morales and D. J. Lenschow, “The antiviral activities of ISG15,” Journal of Molecular Biology, vol. 425, no. 24, pp. 4995–5008, 2013.
[29]
M.-S. Park, A. García-Sastre, J. F. Cros, C. F. Basler, and P. Palese, “Newcastle disease virus V protein is a determinant of host range restriction,” Journal of Virology, vol. 77, no. 17, pp. 9522–9532, 2003.
[30]
M. Sato, H. Suemori, N. Hata et al., “Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-α/β gene induction,” Immunity, vol. 13, no. 4, pp. 539–548, 2000.
