Abstract
Poxviruses use a complex strategy to escape immune control, by expressing immunomodulatory proteins that could limit their use as vaccine vectors. To test the role of poxvirus NF-κB pathway inhibitors A52, B15, and K7 in immunity, we deleted their genes in an NYVAC (New York vaccinia virus) strain that expresses HIV-1 clade C antigens. After infection of mice, ablation of the A52R, B15R, and K7R genes increased dendritic cell, natural killer cell, and neutrophil migration as well as chemokine/cytokine expression. Revertant viruses with these genes confirmed their role in inhibiting the innate immune system. To different extents, enhanced innate immune responses correlated with increased HIV Pol- and Gag-specific polyfunctional CD8 T cell and HIV Env-specific IgG responses induced by single-, double-, and triple-deletion mutants. These poxvirus proteins thus influence innate and adaptive cell-mediated and humoral immunity, and their ablation offers alternatives for design of vaccine vectors that regulate immune responses distinctly.
Original language | English (US) |
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Article number | e00575-17 |
Journal | Journal of Virology |
Volume | 91 |
Issue number | 13 |
DOIs | |
State | Published - Jul 1 2017 |
Externally published | Yes |
Keywords
- Adaptive immunity
- Human immunodeficiency virus
- Immunomodulation
- Innate immunity
- NF-κB
- NYVAC
- Poxvirus
- T cell immunity
- Vaccines
- Vaccinia virus
ASJC Scopus subject areas
- Microbiology
- Immunology
- Insect Science
- Virology