Interleukin-1β receptor expressed by modified vaccinia virus Ankara interferes with interleukin-1β 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-1βR) in MVA (MVAΔIL-1βR) was previously shown to enhance memory T cell function. Here, we investigated the influence of vIL-1βR on blocking interleukin-1beta (IL-1β) upon MVA infection in various antigen presenting cells of murine and human origin, and analyzed whether inflammasome function contributes to IL-1β production in different cell types.


RESULTS
Extending previous studies, immunizing mice with low doses of MVAΔIL-1βR 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-1β upon infection with MVA. Importantly, free IL-1β was only detected in the absence of vIL-1βR. Moreover, MVAΔIL-1βR increased amounts of bioactive IL-1β compared to MVAwt after infection of human THP-1 cells, as detected using a reporter system that only responds to active and free IL-1β. The MVA-mediated induction of IL-1β 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-1β blocking activity leads to increased concentrations of free IL-1β upon infection of murine and human antigen presenting cells; this is likely responsible for enhanced memory T cell activation upon MVAΔIL-1βR immunization of mice. Moreover, our results suggest that MVA-mediated IL-1β induction is a multifactorial process.
Division of Virology, Paul-Ehrlich Institute, Langen, Germany.
Stefan
S
Zimmerling
Zoe
Z
Waibler
Theresa
T
Resch
Gerd
G
Sutter
Astrid
A
Schwantes
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000821:virology*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology* / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology
D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; D014764:Viral Proteins; D014765:Viral Vaccines