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Usage Information

Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection
Liang Cheng, Haisheng Yu, Guangming Li, Feng Li, Jianping Ma, Jingyun Li, Liqun Chi, Liguo Zhang, Lishan Su
Liang Cheng, Haisheng Yu, Guangming Li, Feng Li, Jianping Ma, Jingyun Li, Liqun Chi, Liguo Zhang, Lishan Su
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Research Article AIDS/HIV

Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection

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Abstract

The direct link between sustained type I interferon (IFN-I) signaling and HIV-1–induced immunopathogenesis during chronic infection remains unclear. Here we report studies using a monoclonal antibody to block IFN-α/β receptor 1 (IFNAR1) signaling during persistent HIV-1 infection in humanized mice (hu-mice). We discovered that, during chronic HIV-1 infection, IFNAR blockade increased viral replication, which was correlated with elevated T cell activation. Thus, IFN-Is suppress HIV-1 replication during the chronic phase but are not essential for HIV-1–induced aberrant immune activation. Surprisingly, IFNAR blockade rescued both total human T cell and HIV-specific T cell numbers despite elevated HIV-1 replication and immune activation. We showed that IFNAR blockade reduced HIV-1–induced apoptosis of CD4+ T cells. Importantly, IFNAR blockade also rescued the function of human T cells, including HIV-1–specific CD8+ and CD4+ T cells. We conclude that during persistent HIV-1 infection, IFN-Is suppress HIV-1 replication, but contribute to depletion and dysfunction of T cells.

Authors

Liang Cheng, Haisheng Yu, Guangming Li, Feng Li, Jianping Ma, Jingyun Li, Liqun Chi, Liguo Zhang, Lishan Su

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Usage data is cumulative from December 2024 through December 2025.

Usage JCI PMC
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Figure 440 10
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Citation downloads 108 0
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Total Views 1,516
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