Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs

Liang Cheng, Jianping Ma, Jingyun Li, Dan Li, Guangming Li, Feng Li, Qing Zhang, Haisheng Yu, Fumihiko Yasui, Chaobaihui Ye, Li Chung Tsao, Zhiyuan Hu, Lishan Su, Liguo Zhang

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Abstract

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 cARTtreated 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.

LanguageEnglish (US)
Pages269-279
Number of pages11
JournalJournal of Clinical Investigation
Volume127
Issue number1
DOIs
StatePublished - Jan 3 2017

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Interferon Type I
HIV-1
T-Lymphocytes
Therapeutics
Lymphoid Tissue

ASJC Scopus subject areas

  • Medicine(all)

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Cheng, L., Ma, J., Li, J., Li, D., Li, G., Li, F., ... Zhang, L. (2017). Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs. Journal of Clinical Investigation, 127(1), 269-279. DOI: 10.1172/JCI90745

Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs. / Cheng, Liang; Ma, Jianping; Li, Jingyun; Li, Dan; Li, Guangming; Li, Feng; Zhang, Qing; Yu, Haisheng; Yasui, Fumihiko; Ye, Chaobaihui; Tsao, Li Chung; Hu, Zhiyuan; Su, Lishan; Zhang, Liguo.

In: Journal of Clinical Investigation, Vol. 127, No. 1, 03.01.2017, p. 269-279.

Research output: Contribution to journalArticle

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 2017, 'Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs' Journal of Clinical Investigation, vol. 127, no. 1, pp. 269-279. DOI: 10.1172/JCI90745
Cheng L, Ma J, Li J, Li D, Li G, Li F et al. Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs. Journal of Clinical Investigation. 2017 Jan 3;127(1):269-279. Available from, DOI: 10.1172/JCI90745
Cheng, Liang ; Ma, Jianping ; Li, Jingyun ; Li, Dan ; Li, Guangming ; Li, Feng ; Zhang, Qing ; Yu, Haisheng ; Yasui, Fumihiko ; Ye, Chaobaihui ; Tsao, Li Chung ; Hu, Zhiyuan ; Su, Lishan ; Zhang, Liguo. / Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs. In: Journal of Clinical Investigation. 2017 ; Vol. 127, No. 1. pp. 269-279
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