Poxvirus tropism may not be dependent upon specific cell surface receptors, but rather upon the ability of a given cell to provide intracellular complementing factors needed for productive virus replication, and on the ability of the specific virus to successfully manipulate intracellular signaling networks that regulate cellular antiviral processes following virus entry [28] . APVs have large genomes that would enable them to express unique collections of viral proteins that function as host range factors, which specifically target and manipulate host signaling pathways to establish optimal cellular conditions for viral replication. However, in some cells, especially mammalian cells, APV replication is blocked. This may be due to the ability of APV to specifically activate signalling pathways or mediators, for example interferon pathways, in those cells. The role of mediators and immunopathology of APV is complex and not well understood. However, considering the numerous steps involved in APV morphogenesis, it is relevant to note that these viruses induce several mediators that allow them to survive and interact with the host cells. Some potential mediators have been identified [7] and are awaiting proper functional characterization. These molecules alone may not fully explain the events that have been documented in mammalian cells that have supported the replication of APV [54] . Hence, identification of new mediators that are up or down-regulated in response to APV infected mammalian and avian cells could help advance our knowledge of immune responses against APV and the related immune-mediated pathology and cell tropism. It would be of vital importance to investigate these characteristics further, especially for the cell types that were recently shown to support APV replication [53, 54] .