Molecular and phylogenetic analyses of the first complete genome sequence of Duck hepatitis A virus genotype 2 from India

•The first complete whole genome sequence of DHAV-2 from India and globally, the third genome sequence.•A homology of 93% with previously reported DHAV-2 strains from Taiwan.•Amino acid mutations noticed within the hyper variable region of VP1 protein.•Transmembrane domain was predicted for 2B protein.•Structure modeled for 3D pol protein and 2A2 protein for identification of functional domains. Duck viral hepatitis (DVH) caused by duck hepatitis A virus (DHAV) is a highly contagious and economically important disease of ducklings worldwide. In many parts of the globe, disease outbreaks are reported in spite of vaccinations, probably due to antigenic diversity among DHAV genotypes. We previously reported the first isolation of DHAV-2 (Genotype−2) from ducklings in Tamil Nadu, India. In this study, we discuss the complete genome sequence of this DHAV-2 isolate (OQ862826). The DHAV-2 genome is 7769 bp long, with a 5′-UTR of 653 bp and a 3′-UTR of 366 bp. Phylogenetic analysis showed clustering of the isolate with DHAV-2, exhibiting 93 % nucleotide identity and 97.5 % amino acid identity with the two Taiwanese DHAV-2 strains reported till date. The genome organization, protease cleavage sites, and protein structures were predicted, revealing conserved motifs/domains essential for virus replication and assembly. Comparative analysis with DHAV-1 (genotype−1) and DHAV-3 (genotype−3) revealed distinct antigenic properties, with conserved functional domains, and also variations within structural and nonstructural proteins. Comparison of the VP1 protein sequences revealed diversity between the genotypes. However, a highly conserved B-cell epitope (174LPSPTY179) similar to previous report in DHAV-1 was observed in all the three DHAV-2 strains. The 2A2 protein, 2C protein, and 3D protein exhibited significant conservation. We identified the critical amino acids required for proteolytic enzyme activity of the 3C protein. The absence of serological cross-neutralization between DHAV-1 and DHAV-2 underscores the importance of genotype-specific vaccines. Our findings provide valuable insights of the molecular signatures of DHAV-2 that could be useful for the development of effective vaccines and diagnostic tools.