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NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses

Author:
Di Pilato, Mauro, Mejías-Píérez, Ernesto, Zonca, Manuela, Perdiguero, Beatriz, Gíéómez, Carmen Elena, Trakala, Marianna, Nieto, Jacobo, Níéóéájera, Josíéóé Luis, S. Sorzano, Carlos Oscar, Combadiíéóéáère, Christophe, Pantaleo, Giuseppe, Planelles, Lourdes, Esteban, Mariano
Source:
Proceedings of the National Academy of Sciences of the United States of America 2015 v.112 no.11 pp. E1333
ISSN:
0027-8424
Subject:
CD8-positive T-lymphocytes, Human immunodeficiency virus, Vaccinia virus, antigens, clinical trials, immune response, mice, neutrophils, pathogens, signal transduction, transcription factor NF-kappa B, vaccines, New York
Abstract:
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 NFκB signaling pathway. Triple ablation in modified virus restored NFκB function in macrophages. After virus infection of mice, NFκB pathway activation led to expression of several cytokines/chemokines that increased the migration of neutrophil populations (Nα and Nβ) to the infection site. Nβ 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.
Agid:
2303489