Virulence genes are generally of non-conserved nature and influence the pathological profile of viruses in an infected host. These genes are important in viral evolution and have been used in studies to provide insight into how some poxviruses evolve strategies to ensure their replication [29] . Many of these strategies can be traced back to discoveries made with knockout (KO) viruses, in which a targeted disruption of a specific viral gene produced phenotypic changes reflective of the normal biological function of its protein product. Deletions of some non-conserved genes have also resulted in conditional replication defects in specific cell types [30] , such as the demonstration of spontaneous deletion of host range genes of vaccinia virus resulting in the compromised growth in the mammalian cell [31] . The K1L and C7L genes of vaccinia virus have been shown to be essential for completion of the replication cycle of vaccinia virus in human cells [32, 33] . In a knockout experiment, vaccina virus was unable to complete its replication cycle in Chinese hamster ovary (CHO) cells, since replication was aborted shortly after virus binding and entry, at the stage of intermediate gene expression [34] . But the insertion of another host range gene, CHOhr from cowpox virus into vaccinia virus allowed vaccinia virus to grow in CHO cells in which they are normally restricted [35] [36] [37] . Through use of these techniques, we now have a better understanding of the biology of vaccinia and other poxviruses, including their host range restriction. Although, some major advances have been made in genome sequencing and in vitro characterization of APVs [7, 8, 38, 39] , studies on APV host range genes are scarce. A wide array of gene homologues with likely host range functions such as NK-cell receptors, chemokines, serine protease inhibitors and homologues of genes involved in apoptosis, cell growth, tissue tropism and avian host range, have been identified in APVs, which suggests significant viral adaptation in the avian host [7] . Molecular knockout studies that target identification and further characterization of viral genes involved in regulation of cell proliferation, chromatin remodelling, virulence and apoptosis, in different APV-infected mammalian and avian cells are needed to better understand the tissue tropism and host range characteristics of APVs, including the abortive infection in mammalian cells.