Avian HEV (aHEV) has been considered as causative agent of hepatitis-splenomegaly syndrome (HSS) in chickens. Like other HEV strains, it is single-stranded positive sense RNA virus belonging to Hepeviridae. In the present study we report partial structural homology of ORF3 encoded protein (ORF3P) of Pakistani novel aHEV (Pak naHEV) strain with a kinase 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophos-phokinase (HPPK) which participates in folate biosynthesis in bacteria. This finding is in agreement with the role of ORF3P as multifunctional protein modulating host cell signaling and gene expression to promote viral replication during infection.