Exosomes originating from infection with the cytoplasmic single-stranded RNA virus Rift Valley fever virus (RVFV) protect recipient cells by inducing RIG-I mediated IFN-B response that leads to activation of autophagy

作者：Farhang Alem, Adeyemi A. Olanrewaju, Samson Omole, Heather E. Hobbs, Noor A. Ahsan, Graham Matulis, Christine A. Brantner, Weidong Zhou, Emanuel F. Petricoin, Lance A. Liotta, Massimo Caputi, Sina Bavari, Yuntao Wu, Fatah Kashanchi, Ramin M. Hakami · 发表于：Cell & Bioscience · 年份：2021 · DOI：10.1186/s13578-021-00732-z · 被引用次数：21 · 研究领域：Extracellular vesicles in disease、Inflammasome and immune disorders、Viral Infections and Vectors

BACKGROUND: Although multiple studies have demonstrated a role for exosomes during virus infections, our understanding of the mechanisms by which exosome exchange regulates immune response during viral infections and affects viral pathogenesis is still in its infancy. In particular, very little is known for cytoplasmic single-stranded RNA viruses such as SARS-CoV-2 and Rift Valley fever virus (RVFV). We have used RVFV infection as a model for cytoplasmic single-stranded RNA viruses to address this gap in knowledge. RVFV is a highly pathogenic agent that causes RVF, a zoonotic disease for which no effective therapeutic or approved human vaccine exist. RESULTS: We show here that exosomes released from cells infected with RVFV (designated as EXi-RVFV) serve a protective role for the host and provide a mechanistic model for these effects. Our results show that treatment of both naïve immune cells (U937 monocytes) and naïve non-immune cells (HSAECs) with EXi-RVFV induces a strong RIG-I dependent activation of IFN-B. We also demonstrate that this strong anti-viral response leads to activation of autophagy in treated cells and correlates with resistance to subsequent viral infection. Since we have shown that viral RNA genome is associated with EXi-RVFV, RIG-I activation might be mediated by the presence of packaged viral RNA sequences. CONCLUSIONS: Using RVFV infection as a model for cytoplasmic single-stranded RNA viruses, our results show a novel mechanism of host protection by ex...