Poxviruses have evolved numerous mechanisms to avoid the immune response of the infected host, and many of these mechanisms have not been fully described. Here, we studied the transcriptional response of innate immune genes in BALB/c and C57BL/6 peritoneal macrophages following infection with the Moscow strain of ectromelia virus (ECTV-Mos) with the aim of delineating innate immune genes that contribute to the difference between susceptibility and resistance to lethal infection. We show a generalized downregulation of many genes in four categories (toll-like receptor signaling, NOD-like receptor signaling, RIG-I-like receptor signaling, and type I interferon signaling) of antiviral innate immune receptors, downstream signaling pathways, and responsive components. Two important observations were made. First, 14 innate antiviral genes were differentially expressed with fold change upregulation of two and above occurring in C57BL/6 mice, known to be resistant to ECTV-Mos infection, whereas the same genes were downregulated in BALB/c mice with fold change of two and below. Second, the cathepsin group of genes was downregulated in both strains of mice but with profound fold changes of 17, 38, and 62 downregulation for CtsL, CtsB, and CtsS, respectively, in C57BL/6 mice. We show that a poxvirus profoundly downregulates both the mRNA and protein expression of these three cathepsins and this change appears to support virus replication. Based on these data we propose that the variations in gene expression observed may contribute to the difference in resistance/susceptibility between BALB/c and C57BL/6 mice to lethal infection by ECTV-Mos.

One of the major factors limiting the effectiveness of cancer chemotherapy is inefficient drug delivery. Systems enabling efficient delivery and enhanced intracellular uptake appear particularly promising in this respect. Virus-like particle, adenoviral dodecahedron (Dd), employs receptor-mediated endocytosis for cell penetration and is able to deliver intracellularly dozens of cargo molecules attached to one particle. We focused on studying Dd properties in the context of cancer treatment, showing that intratumoral injection of Dd, assessed in mouse xenograft model, results in vector accumulation in tumor without spreading in off-target organs. Moreover, we demonstrated that Dd is a promising vector targeting leukocytes and drug-resistant cancer cells. Dd uptake by human blood cells analyzed in vitro indicated the preference for leukocytes in comparison to red blood cells and platelets. Furthermore, internalization of Dd-doxorubicin conjugate by drug-resistant cells leads to increased nuclear accumulation of doxorubicin and significant enhancement of cytotoxicity against target cancer cells.

Poxviruses have evolved a number of mechanisms to avoid immune response by the infected host. We investigated the impact of poxvirus infection on the level of mRNA transcripts of selected genes encoding antiviral proteins in the macrophage cell line (RAW 264.7). We observed reduction of mRNA transcript level in four groups of signalling pathways (Toll-like receptor signalling, NOD-like receptor signalling, RIG-I-like receptor signalling, and Type I interferon signalling) involved in innate immune response. Seventy-three genes had a statistically significantly decreased mRNA expression, 4 genes had a statistically significantly sustained mRNA expression. Only Cxcl11 and Ifna2 were statistically significantly increased. The results confirmed that the mouse poxvirus ECTV may interfere with or inhibit many signalling pathways, which are involved in inducing an antiviral immune response in infected macrophages.

Although a few mechanisms have explained how, for instance ectromelia virus (ECTV), is successful in causing fatal disease in certain strains of mice and how other strains are not susceptible, a global transcription overview of innate immunity genes is not entirely known. Poxviruses have evolved several mechanisms to avoid immune response of an infected host. Here we have studied the innate gene transcriptional response of BALB/c and C57BL/6 mice peritoneal macrophages to infection with ECTV Moscow strain (ECTV-Mos). Indeed, assessment of four categories of antiviral innate immune response receptors, downstream signalling and responsive components revealed generalized down regulation of many genes in both strains of mice. Of the 84 genes assessed in each mouse strain only 3 and 15 were significantly upregulated in BALB/c and C57BL/6 mice, respectively. The remaining genes were more or less down-regulated. Surprisingly, type I interferon genes were substantially upregulated. The observed upregulation strongly correlated with protein expression in the case of cathepsin genes as well as TLR genes. ECTV-Mos inhibits receptors and signalling components of the innate immune response in mice. Results provide an insight into initial factors that presumably lead to an ineffective antiviral immune response of BALB/c and C57BL/6 mice in the light of infection with ECTV.