Poxviral E3L ortholog (Viral Interferon resistance gene) of orf viruses of sheep and goats indicates species-specific clustering with heterogeneity among parapoxviruses

Abstract

Orf is a contagious disease posing a serious threat to animal and human health. E3L is one of the evolutionarily acquired immunomodulatory proteins present in orf virus (ORFV) and is responsible for conferring resistance to interferons among poxviruses. Genetic analysis of ORFV isolates of different geographical regions including Indian subcontinent targeting viral interferon resistance (VIR) gene (a homolog of vaccinia virus E3L gene) revealed a high percentage of identity among themselves and other ORFV isolates at both nt and aa levels as compared to low identity among parapoxviruses (PPVs). Phylogenetic analysis showed species-specific clustering among PPVs along with sub-clusters based on host species of origin among ORFVs infecting sheep and goats. Conserved amino acids in N-terminal Z-DNA binding domain and C-terminal ds RNA binding domain of VIR proteins of PPVs corresponding to ORFV VIR positions namely N37, Y41, P57, and W59 (necessary for Z-DNA binding) and E116, F127, F141, and K160 (necessary for dsRNA binding) were found. Further, the predicted protein characteristics and homology model of VIR protein of ORFV showed high structural conservation among poxviruses. This study on E3L genetic analysis of ORFV isolates may provide a better understanding of the molecular epidemiology of circulating strains in India and neighboring countries. Also, E3L deleted or mutated ORFV may be an as vaccine candidate and/or compounds blocking E3L may prove as an effective method for treating broad spectrum poxviral infections, suggesting a wider application in control of poxvirus infections.