Gene expression associated with chicken resistance to infectious bursal disease virus (IBDV)

Infectious Bursal Disease Virus (IBDV) causes highly contagious, immunosuppressive disease that leads to high mortality in young chickens. Chicks of a F2 generation of two lines divergently selected for high (HH) or low (LL) antibody (Ab) response to Escherichia coli vaccination, were challenged with virulent IBDV. Viral load in infected bursae was used to determine resistant (R) and susceptible (S) birds. By using a 13K chicken cDNA microarray, and pooled spleens of R, S and non-challenged, control (C) chicks, several genes were identified with differential expression associated with host resistance to IBDV. These genes were also subjected to RT-PCR on individual samples to verify the results obtained from microarrays. The major finding was the co-upregulation of 7 genes – coding for Ets2, H963, RGS1, ABIN-2, CREM/ICER, DUSP1 and CXCR4 – in several R, but not S or C, individuals, and characterized by very high correlations of expression levels. Resistance also generally coincided with reduced transcript levels of acute-phase serum amyloid A (A-SAA) and increased levels of IL-8. Based on reported functions of these genes, our findings suggest that resistance was mediated by the activation of specific cellular mechanisms, indicated by increased activity of splenic macrophages and T-lymphocytes 3d post-challenge. Early and intense innate responses may enhance the formation and activity of germinal centers in the spleen of resistant birds, and the transition to acquired cellular response. The migration of activated cells towards the bursa is presumably important for resistance to occur. Keywords: host-resistance analysis Male and female chicks (N = 183) were grown under routine management conditions. At 13 days of age, chicks were housed in isolators. At age 21d, 160 chicks were IBDV-challenge and the remaining 23 were grown under the same conditions in a separate isolator and served as non-challenged controls (C). At age 24d (3d PC), all chicks were weighed, bled and euthanized. Spleens and bursae were harvested. Viral load in infected bursae was used to determine resistant (R) and susceptible (S) birds. S, R and C groups were divided into 4 sub-groups (S1-S4, R1-R4 and C1-C4) with similar representation of viral-load scores, so that they were considered biological replicas. These sub-groups were of 2 birds each, except S1 and R1 which were single individuals. Overall, 22 birds were used (7 from R group, 7 from S and 8 from C). Each sub-group was used to create a RNA pool, forming 4 sets of replicated comparisons. Each set consisted of 3 comparisons: R vs. S, R vs. C and S vs. C (overall: 12 comparisons/microarrays). Cy3- and Cy5-labellings of two compared groups were switched in same comparisons in different sets (dye-swaps).