TY - JOUR T1 - HIV-1 Unspliced RNA Expression Induces Innate Immune Activation in Macrophages JF - bioRxiv DO - 10.1101/174508 SP - 174508 AU - Hisashi Akiyama AU - Caitlin M. Miller AU - Chelsea R. Ettinger AU - Anna C. Belkina AU - Jennifer Snyder-Cappione AU - Suryaram Gummuluru Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/08/10/174508.abstract N2 - 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. ER -