| First Author | Di Pilato M | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 11 | Pages | E1333-42 |
| PubMed ID | 25739961 | Mgi Jnum | J:220698 |
| Mgi Id | MGI:5635953 | Doi | 10.1073/pnas.1424341112 |
| Citation | Di Pilato M, et al. (2015) NFkappaB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses. Proc Natl Acad Sci U S A 112(11):E1333-42 |
| abstractText | Neutrophils are antigen-transporting cells that generate vaccinia virus (VACV)-specific T-cell responses, yet how VACV modulates neutrophil recruitment and its significance in the immune response are unknown. We generated an attenuated VACV strain that expresses HIV-1 clade C antigens but lacks three specific viral genes (A52R, K7R, and B15R). We found that these genes act together to inhibit the NFkappaB signaling pathway. Triple ablation in modified virus restored NFkappaB function in macrophages. After virus infection of mice, NFkappaB pathway activation led to expression of several cytokines/chemokines that increased the migration of neutrophil populations (Nalpha and Nbeta) to the infection site. Nbeta cells displayed features of antigen-presenting cells and activated virus-specific CD8 T cells. Enhanced neutrophil trafficking to the infection site correlated with an increased T-cell response to HIV vector-delivered antigens. These results identify a mechanism for poxvirus-induced immune response and alternatives for vaccine vector design. |
