Immunomodulation of Cowpox Virus

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Cowpox virus (CPXV), a double-stranded DNA virus from the Poxviridae family, employs numerous immunomodulatory proteins to evade host immune defenses. These poxviruses excel at mimicry and interaction, targeting innate and acquired immunity mechanisms. To improve upon traditional mutant virus production methods, the complete CPXV genome was cloned into a Bacterial Artificial Chromosome (BAC) in E. coli, allowing for efficient virus tracking via fluorescence with a gfp gene. A second BAC clone facilitated a self-excisable gfp gene, enabling homologous recombination in mammalian cells to remove non-CPXV sequences, resulting in a virus (vBR) that mirrors wild-type without extra markers. This BAC system also allows for the generation of mutant viruses with precise sequence alterations. The 38 kDa protein cytokine response modifier A (CrmA), a serine protease inhibitor with anti-apoptotic and anti-inflammatory properties, was selected for further study due to its role in the red hemorrhagic phenotype of pocks on chicken chorioallantoic membranes (CAMs). While CrmA-positive viruses led to pox accumulation in endothelial cells, a mutant virus with CrmA expressed in a modified vaccinia virus Ankara background produced white pocks instead of red, suggesting that CrmA alone is insufficient for red pock development and that additional viral factors are required.