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

Proceedings of the National Academy of Sciences of the United States of America
Mauro Di PilatoMariano Esteban

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.

References

May 16, 1998·The Journal of Experimental Medicine·L OehlerW Knapp
Aug 2, 2000·Proceedings of the National Academy of Sciences of the United States of America·A BowieL A O'Neill
Feb 5, 2003·The Journal of Experimental Medicine·Mary T HarteLuke A J O'Neill
Mar 6, 2004·Science·Volker BrinkmannArturo Zychlinsky
Feb 25, 2006·Cell·Shizuo AkiraOsamu Takeuchi
Feb 25, 2006·Nature Reviews. Immunology·Carl Nathan
Feb 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yumi HashimotoYoshinobu Nakanishi
Jun 15, 2007·Blood·Céline BeauvillainPascale Jeannin
Sep 22, 2007·Journal of Leukocyte Biology·Jean M DaleyJorge E Albina
Jan 16, 2008·The Journal of Experimental Medicine·Alexandre HarariGiuseppe Pantaleo
Feb 13, 2008·PLoS Pathogens·Ron A-J ChenGeoffrey L Smith
Jul 12, 2008·Nature Reviews. Immunology·Philip J R Goulder, David I Watkins
Aug 15, 2008·Immunity·Mi Sun Jin, Jie-Oh Lee
Aug 23, 2008·Immunity·Tatyana ChtanovaEllen A Robey
Sep 20, 2008·PLoS Pathogens·Martha A HutchensGary D Luker
Oct 22, 2009·The New England Journal of Medicine·Supachai Rerks-NgarmUNKNOWN MOPH-TAVEG Investigators
Aug 4, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chiao-Wen YangEmil R Unanue
Nov 23, 2010·AIDS Research and Human Retroviruses·Otto O YangBeth D Jamieson
Nov 26, 2010·Immunity·Niels Borregaard
Apr 2, 2011·Current Gene Therapy·Carmen E GómezMariano Esteban
Nov 19, 2011·PloS One·Karen V KiblerMariano Esteban
Jul 14, 2012·The Journal of General Virology·Stuart W J EmberGeoffrey L Smith
Aug 22, 2012·Human Vaccines & Immunotherapeutics·Carmen Elena GómezMariano Esteban
Sep 4, 2013·The Journal of General Virology·Geoffrey L SmithRebecca P Sumner
Oct 1, 2013·The Journal of General Virology·Mauro Di PilatoMariano Esteban

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Citations

May 1, 2015·Cell Cycle·Mauro Di Pilato, Mariano Esteban
Jan 10, 2018·Frontiers in Immunology·Ulrich E SchaibleTobias Dallenga
Jan 11, 2019·Journal for Immunotherapy of Cancer·Zong Sheng GuoDavid L Bartlett
Nov 13, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Parna BhattacharyaHira L Nakhasi
Feb 13, 2021·Annals of Surgical Oncology·Chigozirim N EkekeRajeev Dhupar
Dec 3, 2020·Pathogens·Justyna Struzik, Lidia Szulc-Dąbrowska
Apr 14, 2021·NPJ Vaccines·Mauro Di PilatoSantiago F Gonzalez
Aug 29, 2021·Cancer Gene Therapy·David Mealiea, J Andrea McCart

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