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bioRxiv · 10.1101/174508

HIV-1 Unspliced RNA Expression Induces Innate Immune Activation in Macrophages

Akiyama, H.·Miller, C. M.·Ettinger, C. R.·Belkina, A. C.·Snyder-Cappione, J.·Gummuluru, S.
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Abstract

Low-levels of type I interferons (IFN-I) are thought to be a driving force for immune activation and T cell exhaustion in HIV-1 infected individuals on highly active antiretroviral therapy (HAART), though the causative mechanisms for persistent IFN-I signaling have remained unclear. Here, we show Rev-CRM1 dependent nuclear export and peripheral membrane association of intron-containing HIV-1 unspliced RNA (usRNA), independent of primary viral sequence or viral protein expression, is subject to sensing, and results in IFN-I-dependent pro-inflammatory responses in macrophages. Our findings suggest that persistent expression of HIV-1 usRNA in macrophages contributes to chronic immune activation and that use of HIV RNA expression inhibitors as adjunct therapy might abrogate aberrant inflammation and restore immune function in HIV-infected individuals on HAART.

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Akiyama, H., Miller, C. M., Ettinger, C. R., Belkina, A. C., Snyder-Cappione, J., Gummuluru, S.. 2017-08-10. HIV-1 Unspliced RNA Expression Induces Innate Immune Activation in Macrophages. https://doi.org/10.1101/174508

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