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Immune responses to dsRNA: Implications for gene silencing technologies
Author(s) -
Karpala Adam J,
Doran Tim J,
Bean Andrew GD
Publication year - 2005
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/j.1440-1711.2005.01331.x
Subject(s) - rna silencing , biology , rna interference , gene silencing , dicer , immune system , argonaute , nucleic acid , pattern recognition receptor , gene knockdown , innate immune system , small interfering rna , rna , microbiology and biotechnology , gene , genetics
Nucleic acid‐induced gene silencing, such as RNA interference (RNAi), induces a multitude of responses in addition to the knockdown of a gene. This is best understood in the context of the antiviral immune response, from which the processes of RNAi are thought to be derived. Viral challenge of a vertebrate host leads to an intricate series of responses that orchestrate antiviral immunity. The success of this multifaceted system in overcoming viral encounters hinges on complex pathogen–host interactions. One aspect of these interactions, the nucleic acid‐based immune response, is key to the successful resolution of a viral challenge. In particular, dsRNA, a nucleic acid associated with viral replication, is involved in numerous interactions contributing to induction, activation and regulation of antiviral mechanisms. Specifically, dsRNA is responsible for stimulating important protective responses, such as the activation of dicer‐related antiviral pathways, induction of type 1 IFN, and stimulation of dsRNA‐activated protein kinase and oligoadenylate synthetase. Furthermore, the modulation and shaping of this overall immune response is facilitated through nucleic acid interactions with pattern recognition receptors such as toll‐like receptor 3. These diverse dsRNA‐induced antiviral responses have implications for biotechnologies that use dsRNA to harness one arm of the host antiviral machinery for silencing a specific target gene. The interlinked nature of these response elements means that it may be difficult to completely isolate one element from the other arms of the antiviral response program of an organism. Thus, it is beneficial to understand all aspects of the immune response to dsRNA in order to manipulate these systems and minimize unwanted non‐specific effects.