Molecular basis of susceptibility to Newcastle disease virus challenge in exotic and local Tanzanian chicken

A Thesis Submitted in Partial Fulfilment of the Requirements for the Degree of Doctor of Philosophy in Life Sciences of the Nelson Mandela African Institution of Science and Technology, Arusha, TanzaniaThis research aimed to investigate genetic mechanisms of susceptibility to Newcastle disease virus (NDV) in exotic and local Tanzanian chicken. In the first experiment kuroiler, broiler and local Tanzanian chickens were vaccinated with live La Sota Newcastle disease (ND) vaccine, and body weight gain and antibody responses were used as phenotypes to evaluate chicken susceptibility to NDV. Results showed higher (P < 0.05) antibody titres in kuroilers (3.81 ± 0.06) as compared to local chickens (3.73 ± 0.07) and broilers (3.53±0.06) at day 10 post-vaccination. However, antibody titres were not different (P > 0.05) between kuroilers and local Tanzania chickens at day 21 post-vaccination. Although results showed differences between vaccinated and control groups, the results could not give clear cut differences on variations in susceptibility, probably because a less virulent strain of NDV was used and the housing environment might have created some confounding variables. Therefore, in the second experiment virulent NDV and chicken embryo model were used to investigate chickens variation in susceptibility to NDV where time of death post-challenge was used as a phenotype. A total of 355 (87 Sasso, 129 kuroiler and 139 local) 16-day-old chicken embryos were challenged with virulent NDV, and death time was recorded post-challenge. Candidate gene and selective genotyping approaches were deployed, and therefore, chicken embryos from high (15%) and less (15%) susceptible cohorts were genotyped for selected genes (myxovirus resistance gene (Mx) and LEI0258). As expected, chicken embryos survival time was highly variable within a breed. Furthermore, it was demonstrated that chicken Mx gene G2032A genotypes (AA, AG, and GG) were associated (P < 0.05) with susceptibility. Interestingly, for the first time, findings demonstrated an association between chicken Mx gene promoter polymorphisms and chicken embryos susceptibility to virulent NDV. Specifically, SNP4 G>A mutation located within IFN-stimulating response element was associated (LR: 6.97, P = 0.03) with susceptibility. Also, haplotype ACGC was associated (OR: 9.8, 95% CI: 1.06 – 79.43, P = 0.042) with the same trait, and had a protective effect. The present findings are very useful in breeding programs designed to develop chicken genotypes, which are less susceptible to NDV