Project description:The 2022 North American outbreak of 2.3.4.4b H5N1 avian influenza virus revealed significant mammalian adaptation and pathogenicity, yet mechanisms remain unclear. To address this knowledge gap, we investigated the North American H5N1 strain (GA/W22-145E/22), which demonstrated unique immune cell-mediated systemic dissemination, neuroinvasion, and 100% mortality in ferrets, unlike the non-lethal Eurasian strain (KR/W811/21). Genomic and reverse genetics studies identified PB2478I and NP450N mutations as key determinants of enhanced polymerase activity, immune cell tropism, and pathogenicity. Mutant GA/W22-145E/22 virus carrying PB2478V/NP450S showed complete survival without systemic dissemination. Furthermore, GA/W22-145E/22 demonstrated robust replication in human PBMCs and bovine mammary gland organoids, raising concerns about zoonotic spillover. These findings underscore PB2478I and NP450N as pivotal markers of pathogenicity, emphasizing the urgent need for enhanced surveillance and targeted interventions
Project description:For genomic selection to be successful, there must be sufficient linkage disequilibrium between the markers and the causal mutations. The objectives of this study were to evaluate the extent of LD in ovine using the Santa Inês breed and to infer the minimum number of markers required to reach reasonable prediction accuracy. In total, 38,168 SNPs and 395 samples were used. The mean LD between adjacent marker pairs measured by r2 and |D'| were 0.166 and 0.617, respectively. LD values between adjacent marker pairs ranged from 0.135 to 0.194 and from 0.568 to 0.650 for r2 for |D'| across all chromosomes. The average r2 between all pairwise SNPs on each chromosome was 0.018. SNPs separated by between 0.10 to 0.20 Mb had an estimated average r2 equal to 0.1033. The identified haplotype blocks consisted of 2 to 21 markers. Moreover, estimates of average coefficients of inbreeding and effective population size were 0.04 and 96, respectively. LD estimated in this study was lower than that reported in other species and was characterized by short haplotype blocks. Our results suggest that the use of a higher density SNP panel is recommended for the implementation of genomic selection in the Santa Inês breed.