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HIV triggers a cGAS-dependent, Vpu- and Vpr-regulated type I interferon response in CD4+ T cells

(2016) CELL REPORTS. 17(2). p.413-424
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Abstract
Several pattern recognition receptors sense HIV-1 replication products and induce type I interferon (IFN-I) production under specific experimental conditions. However, it is thought that viral sensing and IFN induction are virtually absent in the main target cells of HIV-1 in vivo. Here, we show that activated CD4+ T cells sense HIV-1 infection through the cytosolic DNA sensor cGAS and mount a bioactive IFN-I response. Efficient induction of IFN-I by HIV-1 infection requires proviral integration and is regulated by newly expressed viral accessory proteins: Vpr potentiates, while Vpu suppresses cGAS-dependent IFN-I induction. Furthermore, Vpr also amplified innate sensing of HIV-1 infection in Vpx treated dendritic cells. Our results identify cGAS to mediate IFN-I response to HIV-1 infection in CD4+ T cells and demonstrate that this response is modulated by the viral accessory proteins Vpr and Vpu. Thus, viral innate immune evasion is incomplete in the main target cell of HIV-1.
Keywords
HIV, cGAS, T-cells, dendritic cells, Interferon, Vpr, Vpu, NF-KAPPA-B, IMMUNODEFICIENCY-VIRUS TYPE-1, INNATE IMMUNE-RESPONSE, DENDRITIC CELLS, DISEASE PROGRESSION, PROTEIN-R, INFECTION, SENSOR, REPLICATION, EXPRESSION

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MLA
VERMEIRE, JOLIEN et al. “HIV Triggers a cGAS-dependent, Vpu- and Vpr-regulated Type I Interferon Response in CD4+ T Cells.” CELL REPORTS 17.2 (2016): 413–424. Print.
APA
VERMEIRE, J., Roesch, F., Sauter, D., Rua, R., Hotter, D., Van Nuffel, A., Vanderstraeten, H., et al. (2016). HIV triggers a cGAS-dependent, Vpu- and Vpr-regulated type I interferon response in CD4+ T cells. CELL REPORTS, 17(2), 413–424.
Chicago author-date
VERMEIRE, JOLIEN, Ferdinand Roesch, Daniel Sauter, Réjane Rua, Dominik Hotter, Anouk Van Nuffel, Hanne Vanderstraeten, et al. 2016. “HIV Triggers a cGAS-dependent, Vpu- and Vpr-regulated Type I Interferon Response in CD4+ T Cells.” Cell Reports 17 (2): 413–424.
Chicago author-date (all authors)
VERMEIRE, JOLIEN, Ferdinand Roesch, Daniel Sauter, Réjane Rua, Dominik Hotter, Anouk Van Nuffel, Hanne Vanderstraeten, Evelien Naessens, Veronica Iannucci, Alessia Landi, Wojciech Witkowski, Ann Baeyens, Frank Kirchhoff, and Bruno Verhasselt. 2016. “HIV Triggers a cGAS-dependent, Vpu- and Vpr-regulated Type I Interferon Response in CD4+ T Cells.” Cell Reports 17 (2): 413–424.
Vancouver
1.
VERMEIRE J, Roesch F, Sauter D, Rua R, Hotter D, Van Nuffel A, et al. HIV triggers a cGAS-dependent, Vpu- and Vpr-regulated type I interferon response in CD4+ T cells. CELL REPORTS. 2016;17(2):413–24.
IEEE
[1]
J. VERMEIRE et al., “HIV triggers a cGAS-dependent, Vpu- and Vpr-regulated type I interferon response in CD4+ T cells,” CELL REPORTS, vol. 17, no. 2, pp. 413–424, 2016.
@article{8103111,
  abstract     = {Several pattern recognition receptors sense HIV-1 replication products and induce type I interferon (IFN-I) production under specific experimental conditions. However, it is thought that viral sensing and IFN induction are virtually absent in the main target cells of HIV-1 in vivo. Here, we show that activated CD4+ T cells sense HIV-1 infection through the cytosolic DNA sensor cGAS and mount a bioactive IFN-I response. Efficient induction of IFN-I by HIV-1 infection requires proviral integration and is regulated by newly expressed viral accessory proteins: Vpr potentiates, while Vpu suppresses cGAS-dependent IFN-I induction. Furthermore, Vpr also amplified innate sensing of HIV-1 infection in Vpx treated dendritic cells. Our results identify cGAS to mediate IFN-I response to HIV-1 infection in CD4+ T cells and demonstrate that this response is modulated by the viral accessory proteins Vpr and Vpu. Thus, viral innate immune evasion is incomplete in the main target cell of HIV-1.},
  author       = {VERMEIRE, JOLIEN and Roesch, Ferdinand and Sauter, Daniel and Rua, Réjane and Hotter, Dominik and Van Nuffel, Anouk and Vanderstraeten, Hanne and Naessens, Evelien and Iannucci, Veronica and Landi, Alessia and Witkowski, Wojciech and Baeyens, Ann and Kirchhoff, Frank and Verhasselt, Bruno},
  issn         = {2211-1247},
  journal      = {CELL REPORTS},
  keywords     = {HIV,cGAS,T-cells,dendritic cells,Interferon,Vpr,Vpu,NF-KAPPA-B,IMMUNODEFICIENCY-VIRUS TYPE-1,INNATE IMMUNE-RESPONSE,DENDRITIC CELLS,DISEASE PROGRESSION,PROTEIN-R,INFECTION,SENSOR,REPLICATION,EXPRESSION},
  language     = {eng},
  number       = {2},
  pages        = {413--424},
  title        = {HIV triggers a cGAS-dependent, Vpu- and Vpr-regulated type I interferon response in CD4+ T cells},
  url          = {http://dx.doi.org/10.1016/j.celrep.2016.09.023},
  volume       = {17},
  year         = {2016},
}

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