Preview

NDV Induced Immune-Pathology in Chickens

Hu Zenglei1 and Xiufan Liu1, 2*

1Animal Infectious Disease Laboratory, School of Veterinary Medicine; 2Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China.

Editor | Muhammad Munir, The Pirbright Institute, Compton Laboratory, UK.

Received | March 02, 2015; Accepted | March 25, 2015; Published | March 27, 2015

*Correspondence | Xiufan Liu, Yangzhou University, 48 East Wenhui Road, Yangzhou, Jiangsu, China; E-mail | [email protected]

Citation | Zenglei, H. and X. Liu. 2015. Immune response-induced NDV pathology. British Journal of Virology, 2(2): 25-27.

Newcastle disease virus (NDV) varies greatly in their virulence or pathogenicity for chickens and based on this difference NDV strains are classified into three pathotypes: velogene, mesogene and lentogene (Alexander, 2003). The virus is rapidly evolving, and several new velogenic genotypes have been discovered in the past two decades. Both the severity of disease and the pathological changes induced by NDV are dependent on multiple factors associated with pathogen, host and environment, while the most important factor is the virulence of the infected strain. It is generally accepted that the cleavage site in the fusion (F) protein is the primary molecular determinant of NDV virulence (Dortmans et al., 2011; Peeters et al., 1999). However, more recent studies have shown that virulent strains of different genetypes sharing similar F cleavage site associated with high virulence produce distinct pathological manifestation in chickens, especially in lymphoid tissues (Ecco et al., 2011; Merino et al., 2011; Susta et al., 2011; Wang et al., 2012).

Furthermore, results from independent studies have shown that velogenic NDV strains induce strong innate immune response evidenced by up-regulation of groups of genes associated with the innate antiviral and inflammatory responses which correlates to the high mortality or severe pathological damage, indicating its contribution in the pathogenesis (Liu et al., 2012; Rue et al., 2011). Comparative studies with different pathotypes of NDVs showed that the magnitude of innate immune response is mainly related to virulence.

As mentioned above, virulent NDV strains of different genotypes may induce distinct pathological changes. For instance, genotype VIId virus which is currently endemic in many countries (Ebrahimi et al., 2012; Liu et al., 2003; Mase et al., 2002; Qin et al., 2008) induce more severe damage in lymphoid tissues featured by severe lymphocytic depletion, histiocytic accumulation and necrosis of the spleen and thymus when compared with virulent viruses of other genotypes (Susta et al., 2011; Wang et al., 2012; Hu et al., 2015). More recent studies demonstrated that the high level of virus replication and intense innate immune response contribute to the severe pathology in lymphoid tissues caused by NDV of genotype VIId (Ecco et al., 2011; Hu et al., 2012; Hu et al., 2015). A common finding from these studies is that the extent of the innate immune response which correlates with the efficiency of virus replication in target organs. Most likely, genotype VIId strains of NDV replicate at higher levels in lymphoid tissues and release more viral components that would be recognized by pattern recognition receptors (PRRs), resulting in the over-activated innate immune response. Strong antiviral and pro-inflammatory responses induced by genotype VIId of NDV, or immunopathology, is an indispensable part of its pathogenesis, very similar to the “cytokine storm” in the pathogenesis of highly pathogenic avian influenza viruses (Baskin et al., 2009; Tisoncik et al., 2012).

Recently, Cornax et al. ( 2013) demonstrated that the fusion (F) and haemagglutinin-neuraminidase (HN) proteins are major determinants of NDV responsible for the replication capacity in macrophages. In addition, using gene-swapping strategy, we have recently identified that the matrix (M), F and HN genes together determine the high level of replication and intense innate response, and thus the severe pathology, in the spleen caused by genotype VIId strains of NDV (Hu et al. unpublished data). To further elucidate viral replication and innate immune response in the pathogenesis of NDV infection, it is necessary to characterize the interaction between individual viral proteins or their functional domain and the factors involved in the innate immune pathway.

Furthermore, the innate immune response may also affect NDV pathology through its interplay with apoptosis. NDV infection induces directly apoptosis resulting in the histologic changes such as lymphocyte depletion or necrosis in lymphoid tissues (Harrison et al., 2011; Kommers et al., 2003; Kommers et al., 2002). In our studies, genotype VIId strains of NDV induce more apparent apoptosis in chicken splenocytes (Hu et al., 2012) and up-regulate genes associated with apoptosis in the spleen when compared to genotype IV strains of NDV (Hu et al., 2015), suggesting the involvement of apoptosis in NDV pathology. On the other hand, in addition to the function in antiviral activity, some cytokines, such as interferons (IFNs), also serve as key mediators of apoptosis. Many factors in IFN signaling pathway, including IFN regulatory factor, protein kinase R and 2’,5-oligoadenylate/RNaseL system, contribute to apoptosis through different mechanisms (Barber, 2001). The IFNs can also activate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that initiates the death receptor-mediated cell death (Barber, 2001). Thus, one possible secondary effect of the hyper-induction of the innate immune response may be the enhanced apoptosis, which may further deteriorate NDV pathology. Therefore, the relationship between the innate response, apoptosis and pathological manifestation caused by NDV deserve additional studies. Understanding these complex host pathogen interactions would help to underpin some of the key cellular interactors that are fundamental to the pathogenesis of NDV. Once highlighted, these specific pathways may pave the way for defining future control strategies of NDV and may help to reduce the economic burden caused by this deadly disease especially in the countries where biosecurity is not up-to-date and the disease is endemic.

References

• Alexander, D. J., 2003: Newcastle Disease, Other Avian Paramyxoviruses, and Pneumovirus Infections. In Diseases of poultry, 11th edn, pp. 63-87. Edited by Y. M. Saif. Ames, IA: Iowa State University Press.
• Barber, G. N. Host defense, viruses and apoptosis. Cell Death Differ, 2001; 8(2): 113-26.
• Baskin, C. R., Bielefeldt-Ohmann, H., Tumpey, T. M., Sabourin, P. J., Long, J. P., Garcia-Sastre, A., Tolnay, A. E., Albrecht, R., Pyles, J. A., Olson, P. H., Aicher, L. D., Rosenzweig, E. R., Murali-Krishna, K., Clark, E. A., Kotur, M. S., Fornek, J. L., Proll, S., Palermo, R. E., Sabourin, C. L. Katze, M. G. Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus. Proc Natl Acad Sci USA, 2009; 106(9): 3455-3460.
• Cornax, I., Diel, D. G., Rue, C. A., Estevez, C., Yu, Q., Miller, P. J. Afonso, C. L. Newcastle disease virus fusion and haemagglutinin-neuraminidase proteins contribute to its macrophage host range. J Gen Virol, 2013; 94(Pt 6): 1189-1194.
• Dortmans, J. C. F. M., Koch, G., Rottier, P. J. M. Peeters, B. P. H. Virulence of newcastle disease virus: what is known so far? Vet Res, 2011; 42(1): 122.
• Ebrahimi, M. M., Shahsavandi, S., Moazenijula, G. Shamsara, M. Phylogeny and evolution of Newcastle disease virus genotypes isolated in Asia during 2008-2011. Virus genes, 2012; 45(1): 63-8.
• Ecco, R., Brown, C., Susta, L., Cagle, C., Cornax, I., Pantin-Jackwood, M., Miller, P. J. Afonso, C. L. In vivo transcriptional cytokine responses and association with clinical and pathological outcomes in chickens infected with different Newcastle disease virus isolates using formalin-fixed paraffin-embedded samples. Vet Immunol Immunopathol, 2011; 141(3-4): 221-9.
• Harrison, L., Brown, C., Afonso, C., Zhang, J. Susta, L. Early occurrence of apoptosis in lymphoid tissues from chickens infected with strains of Newcastle disease virus of varying virulence. J Comp Pathol, 2011; 145(4): 327-35.
• Hu, Z., Hu, J., Hu, S., Liu, X., Wang, X., Zhu, J. Liu, X. Strong innate immune response and cell death in chicken splenocytes infected with genotype VIId Newcastle disease virus. Virol J, 2012; 9:208.
• Hu, Z., Hu, J., Hu, S., Song, Q., Ding, P., Zhu, J., Liu, X. Wang, X. High levels of virus replication and an intense inflammatory response contribute to the severe pathology in lymphoid tissues caused by Newcastle disease virus genotype VIId. Arch Virol, 2015; 160(3): 639-48.
• Kommers, G. D., King, D. J., Seal, B. S. Brown, C. C. Pathogenesis of chicken-passaged Newcastle disease viruses isolated from chickens and wild and exotic birds. Avian Dis, 2003; 47(2): 319-29.
• Kommers, G. D., King, D. J., Seal, B. S., Carmichael, K. P. Brown, C. C. Pathogenesis of Six Pigeon-Origin Isolates of Newcastle Disease Virus for Domestic Chickens. Vet Pathol, 2002; 39(3): 353-62.
• Liu, W. Q., Tian, M. X., Wang, Y. P., Zhao, Y., Zou, N. L., Zhao, F. F., Cao, S. J., Wen, X. T., Liu, P. Huang, Y. The different expression of immune-related cytokine genes in response to velogenic and lentogenic Newcastle disease viruses infection in chicken peripheral blood. Mol Biol Rep, 2012; 39(4): 3611-8.
• Liu, X. F., Wan, H. Q., Ni, X. X., Wu, Y. T. Liu, W. B. Pathotypical and genotypical characterization of strains of Newcastle disease virus isolated from outbreaks in chicken and goose flocks in some regions of China during 1985-2001. Arch Virol, 2003; 148(7): 1387-1403.
• Mase, M., Imai, K., Sanada, Y., Sanada, N., Yuasa, N., Imada, T., Tsukamoto, K. Yamaguchi, S. Phylogenetic Analysis of Newcastle Disease Virus Genotypes Isolated in Japan. J Clin Microbiol, 2002; 40(10): 3826-30.
• Merino, R., Villegas, H., Quintana, J. A. Calderon, N. Comparison of the Virulence of Pathogenic Newcastle Disease Viruses Belonging to the Same or Different Genotypes. Int J Poult Sci, 2011; 10(9): 713-20.
• Peeters, B. P., de Leeuw, O. S., Koch, G. Gielkens, A. L. Rescue of Newcastle disease virus from cloned cDNA: evidence that cleavability of the fusion protein is a major determinant for virulence. J Virol, 1999; 73(6): 5001-9.
• Qin, Z. M., Tan, L. T., Xu, H. Y., Ma, B. C., Wang, Y. L., Yuan, X. Y. Liu, W. J. Pathotypical characterization and molecular epidemiology of Newcastle disease virus isolates from different hosts in China from 1996 to 2005. J Clin Microbiol, 2008; 46(2): 601-11.
• Rue, C. A., Susta, L., Cornax, I., Brown, C. C., Kapczynski, D. R., Suarez, D. L., King, D. J., Miller, P. J. Afonso, C. L. Virulent Newcastle disease virus elicits a strong innate immune response in chickens. J Gen Virol, 2011; 92(Pt 4): 931-9.
• Susta, L., Miller, P. J., Afonso, C. L. Brown, C. C. Clinicopathological characterization in poultry of three strains of Newcastle disease virus isolated from recent outbreaks. Vet Pathol, 2011; 48(2): 349-60.
• Tisoncik, J. R., Korth, M. J., Simmons, C. P., Farrar, J., Martin, T. R. Katze, M. G. Into the Eye of the Cytokine Storm. Microbiol Mol Biol Rev, 2012; 76(1): 16-32.
• Wang, Y., Duan, Z., Hu, S., Kai, Y., Wang, X., Song, Q., Zhong, L., Sun, Q., Wu, Y. Liu, X. Lack of detection of host associated differences in Newcastle disease viruses of genotype VIId isolated from chickens and geese. Virol J, 2012; 9(1): 197.