The ability of viruses to control and/or evade the host antiviral response is critical to the establishment of a productive infection. One of the strategies utilized by West Nile virus (WNV) to circumvent the host response is to evade detection by the pathogen recognition receptor RIG-I early in infection. To begin elucidating the mechanisms by which WNV eludes detection, we undertook a systematic analysis of the WNV genome and antigenome to identify RIG-I-specific pathogen associated molecular patterns (PAMPs). Multiple segments of the WNV genome and anitigenome induced a RIG-I-specific antiviral response. However, incorporation of the stimulatory regions into larger RNAs substantially reduced their capacity to activate RIG-I. These results suggested that WNV evades the host response by sequestering RIG-I-specific PAMPs within the complete genome and antigenome at early times post-infection. Furthermore, activation of the RIG-I pathway may require the liberation of PAMPs by the cell's normal RNA processing pathways.
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