The antiviral effects of extracellular dsRNA
Stephanie J. DeWitte-Orr and Karen L. Mossman
from: Viruses and Interferon: Current Research (Edited by: Karen Mossman). Caister Academic Press, U.K. (2011)
Viral double-stranded RNA (dsRNA), a replication by-product of almost all viruses, has been studied for over 55 years, first as a toxin, then as a type I IFN inducer, a viral mimetic and an immunomodulator for therapeutic purposes. Not only does dsRNA function as a pathogen associated molecular pattern (PAMP), sensed by host germline encoded pattern recognition receptors (PRRs) to stimulate innate immune responses, it also acts as a bridge to activate antiviral adaptive immune responses. DsRNA is generated intracellularly during a virus infection, but is released into the extracellular space during cell lysis. This review will focus on the structure and generation (both endogenous and viral) of extracellular dsRNA, and the host sensing mechanisms that result in type I IFN- and RNAi-mediated antiviral responses. The possible therapeutic applications of these findings will also be discussed. The goal of this review is to highlight the importance of this unique nucleic acid, with a focus on how its extracellularity influences its effects on the host and how these effects can be manipulated for our therapeutic purposes read more ...