Molecular characterization, evolutionary dynamics, and pathogenic assessment of chicken infectious anemia virus isolates circulating in Egyptian poultry.

As a result of its severe immunosuppressive nature, CIAV persists as a critical pathogen causing substantial economic concerns in global poultry production. The emergence of genetic variants and reports of suspected vaccine sub-optimal protection in Egyptian broiler flocks necessitates an urgent investigation of currently circulating strains. In this study, 165 samples were collected from six Egyptian governorates (2024-2025). PCR screening revealed 38 positive cases, and six isolates were selected for full-length sequencing of the VP1 and VP2 genes. Molecular analysis identified the isolates as Genotype II, showing significant genetic drift from Genotype I vaccinal strains. Key nonsynonymous mutations, notably H22Q in VP1, suggested potential antigenic escape, while the VP2 gene maintained 100% amino acid identity despite multiple silent mutations. Experimentally, the Genotype II isolate exhibited extreme virulence in SPF chickens; infected birds suffered from severe growth retardation (p < 0.0001) and profound lymphoid organ atrophy, with thymus weights dropping to 1.1 ± 0.07 g. Severe aplastic anemia was confirmed by a dramatic decline in PCV% (19.33 ± 1.45%) and pale, gelatinous bone marrow. Viral load quantification revealed massive replication in the thymus (9.5 Log₁₀) and bone marrow (9 Log₁₀), leading to a total collapse of humoral immunity, with antibody levels falling below the positivity threshold by the 4th week and reaching undetectable levels (S/P 0) by the 5th week post-infection. Histopathology corroborated these findings, showing systemic lymphocyte depletion and characteristic intranuclear inclusion bodies. These findings confirm the emergence of highly pathogenic Genotype II CIAV in Egypt. The ability of these variants to bypass existing immunity highlights the critical need for updating current vaccination strategies and implementing more robust biosecurity measures.