B7-H6-mediated downregulation of NKp30 in natural killer cells contributes to HIV-2 immune escape

Abstract : OBJECTIVE: HIV-1 and HIV-2 differ notably in their epidemiology, with worldwide HIV-1 spread and HIV-2 mainly confined to West Africa. Natural killer (NK) cells are critical antiviral effectors of the immune system; however, limited information is available about these innate effector cells during HIV-2 infection. METHOD: In this study, 24 untreated HIV-2-infected patients were analyzed and compared with 21 long-term nonprogressor and 10 controller HIV-1 patients, and healthy donors. Extensive phenotype and functional NK-cell characteristics, as well as ligands of activating NK receptors involved in NK lysis were determined by flow cytometry. RESULTS: We report in HIV-2 patients a very significant reduced expression of the activating NKp30 receptor (P < 0.0001) on NK cells, much higher than observed in HIV-1 patients. The impaired expression of NKp30 is correlated negatively with HLA-DR (r = -0.5970; P = 0.0002), and positively with both NKG2A (r = 0.5324; P < 0.0001) and Siglec-7 (r = 0.5621; P = 0.0004). HIV-2 patients with NKp30 NK cells displayed overproduction of IFN-γ (P < 0.0001) associated with impaired cytolytic function when tested against target cells expressing surface B7-H6. This cellular ligand of NKp30 is strongly detectable as a surface molecule on CD4 T cells infected by HIV-2. CONCLUSION: Altogether, our data suggested that the defective expression of NKp30 may be induced by the chronic engagement of this receptor by B7-H6 expressed on HIV-2-infected target cells. This represents a novel mechanism by which the chronic ligand exposure by the viral environment may subvert NK-cell-mediated function to establish persistent HIV-2 infection.
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Submitted on : Monday, October 7, 2019 - 1:03:56 PM
Last modification on : Thursday, October 17, 2019 - 4:04:35 PM

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Olivier Lucar, Mariama Sadjo Diallo, Charles Bayard, Assia Samri, Nadine Tarantino, et al.. B7-H6-mediated downregulation of NKp30 in natural killer cells contributes to HIV-2 immune escape. AIDS, Lippincott, Williams & Wilkins, 2019, 33 (1), pp.23-32. ⟨10.1097/QAD.0000000000002061⟩. ⟨hal-02307134⟩

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