Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs.
| Autor: | Cheng L, Ma J, Li J, Li D, Li G, Li F, Zhang Q, Yu H, Yasui F, Ye C, Tsao LC, Hu Z, Su L, Zhang L |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of clinical investigation [J Clin Invest] 2017 Jan 03; Vol. 127 (1), pp. 269-279. Date of Electronic Publication: 2016 Dec 12. |
| DOI: | 10.1172/JCI90745 |
| Abstrakt: | Despite the efficient suppression of HIV-1 replication that can be achieved with combined antiretroviral therapy (cART), low levels of type I interferon (IFN-I) signaling persist in some individuals. This sustained signaling may impede immune recovery and foster viral persistence. Here we report studies using a monoclonal antibody to block IFN-α/β receptor (IFNAR) signaling in humanized mice (hu-mice) that were persistently infected with HIV-1. We discovered that effective cART restored the number of human immune cells in HIV-1-infected hu-mice but did not rescue their immune hyperactivation and dysfunction. IFNAR blockade fully reversed HIV-1-induced immune hyperactivation and rescued anti-HIV-1 immune responses in T cells from HIV-1-infected hu-mice. Finally, we found that IFNAR blockade in the presence of cART reduced the size of HIV-1 reservoirs in lymphoid tissues and delayed HIV-1 rebound after cART cessation in the HIV-1-infected hu-mice. We conclude that low levels of IFN-I signaling contribute to HIV-1-associated immune dysfunction and foster HIV-1 persistence in cART-treated hosts. Our results suggest that blocking IFNAR may provide a potential strategy to enhance immune recovery and reduce HIV-1 reservoirs in individuals with sustained elevations in IFN-I signaling during suppressive cART. Competing Interests: The authors have declared that no conflict of interest exists. |
| Databáze: | MEDLINE |
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