Interleukin-1ß receptor expressed by modified vaccinia virus Ankara interferes with interleukin-1ß activity produced in various virus-infected antigen-presenting cells.

BACKGROUND: Modified vaccinia virus Ankara (MVA) is a highly attenuated virus and a promising vaccine vector with potent immune stimulating properties. Deletion of the gene encoding the viral interleukin-1beta receptor (vIL-1ßR) in MVA (MVAΔIL-1ßR) was previously shown to enhance memory T cell function. Here, we investigated the influence of vIL-1ßR on blocking interleukin-1beta (IL-1ß) upon MVA infection in various antigen presenting cells of murine and human origin, and analyzed whether inflammasome function contributes to IL-1ß production in different cell types. FINDINGS: Extending previous studies, immunizing mice with low doses of MVAΔIL-1ßR still showed enhanced memory CD8(+) T cell activation compared to MVA wild-type (MVAwt) immunization. In vitro, murine myeloid dendritic cells, and activated, but not naive primary macrophages were identified as potent producers of IL-1ß upon infection with MVA. Importantly, free IL-1ß was only detected in the absence of vIL-1ßR. Moreover, MVAΔIL-1ßR increased amounts of bioactive IL-1ß compared to MVAwt after infection of human THP-1 cells, as detected using a reporter system that only responds to active and free IL-1ß. The MVA-mediated induction of IL-1ß was confirmed to depend on inflammasome function in human and murine cells, however in murine cells this apparently involves caspase-1-independent pathways. CONCLUSIONS: MVA lacking IL-1ß blocking activity leads to increased concentrations of free IL-1ß upon infection of murine and human antigen presenting cells; this is likely responsible for enhanced memory T cell activation upon MVAΔIL-1ßR immunization of mice. Moreover, our results suggest that MVA-mediated IL-1ß induction is a multifactorial process.

Testes-specific hemoglobins in Drosophila evolved by a combination of sub- and neofunctionalization after gene duplication.

BACKGROUND: For a long time the presence of respiratory proteins in most insects has been considered unnecessary. However, in recent years it has become evident that globins belong to the standard repertoire of the insect genome. Like most other insect globins, the glob1 gene of Drosophila melanogaster displays a conserved expression pattern in the tracheae, the fat body and the Malpighian tubules. RESULTS: Here we show that the recently discovered D. melanogaster globin genes glob2 and glob3 both display an unusual male-specific expression in the reproductive tract during spermatogenesis. Both paralogs are transcribed at equivalent mRNA levels and largely overlap in their cellular expression patterns during spermatogenesis. Phylogenetic analyses showed that glob2 and glob3 reflect a gene duplication event that occurred in the ancestor of the Sophophora subgenus at least 40 million years ago. Therefore, flies of the Drosophila subgenus harbor only one glob2/3-like gene. CONCLUSIONS: Phylogenetic and sequence analyses indicate an evolution of the glob2 and glob3 duplicates by a combination of sub- and neofunctionalization. Considering their restricted, testes-specific expression, an involvement of both globins in alleviating oxidative stress during spermatogenesis is conceivable.