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Nodamura virus (NoV) lethally infects suckling mice and contains a segmented positive-strand RNA genome that encodes a potent suppressor of RNA interference (RNAi). Recent studies have demonstrated immune detection and subsequent processing of NoV dsRNA replicative intermediates by the mouse RNAi machinery. However, diverse RNA viruses, including Encephalomyocarditis virus that also triggers Dicer-dependent biogenesis of viral siRNAs in mouse cells, are targeted in mammals by RIG-I-like receptors that initiate an IFN-dependent antiviral response. Using mouse embryonic fibroblasts (MEFs) for NoV infection, here we show that MEFs derived from mice knockout for RIG-I, but not those knockout for MDA5, LGP2, TLR3 or TLR7, exhibited an enhanced susceptibility to NoV. Further studies indicate that NoV infection induced an IFN-dependent antiviral response mediated by RIG-I. Our findings suggest that RIG-I directs a typical IFN-dependent antiviral response against an RNA virus capable of suppressing the RNAi response.

Individuals diagnosed with autism often display alterations in visual spatial attention toward visual stimuli, but the underlying cause of these differences remains unclear. Recent evidence has demonstrated that covert spatial attention, rather than remaining constant at a cued location, samples stimuli rhythmically at a frequency of 4–8 Hz (theta). Here we tested whether rhythmic sampling of attention is altered in autism. Participants were asked to monitor three locations to detect a brief target presented 300–1200 ms after a spatial cue. Visual attention was oriented to the cue and modified visual processing at the cued location, consistent with previous studies. We measured detection performance at different cue‐target intervals when the target occurred at the cued location. Significant oscillations in detection performance were identified using both a traditional time‐shuffled approach and a new autoregressive surrogate method developed by Brookshire in 2022. We found that attention enhances behavioral performance rhythmically at the same frequency in both autism and control group at the cued location. However, rhythmic temporal structure was not observed in a subgroup of autistic individuals with co‐occurring attention‐deficit/hyperactivity disorder (ADHD). Our results imply that intrinsic brain rhythms which organize neural activity into alternating attentional states is functional in autistic individuals, but may be altered in autistic participants who have a concurrent ADHD diagnosis. Lay Summary: Many people with autism struggle with shifting their attention from one task or object to another, which can make it challenging for them to switch between different topics or activities. However, our study showed that attention switches between objects in the same way in adults with and without autism. These results imply that a fundamental temporal property of spatial attention is not changed in autistic adults. [ABSTRACT FROM AUTHOR]

Diverse eukaryotic hosts produce virus-derived small interfering RNAs (siRNAs) to direct antiviral immunity by RNA interference (RNAi). However, it remains unknown whether the mammalian RNAi pathway has a natural antiviral function. Here, we show that infection of hamster cells and suckling mice by Nodamura virus (NoV), a mosquito-transmissible RNA virus, requires RNAi suppression by its B2 protein. Loss of B2 expression or its suppressor activity leads to abundant production of viral siRNAs and rapid clearance of the mutant viruses in mice. However, viral small RNAs detected during virulent infection by NoV do not have the properties of canonical siRNAs. These findings have parallels with the induction and suppression of antiviral RNAi by the related Flock house virus in fruit flies and nematodes and reveal a mammalian antiviral immunity mechanism mediated by RNAi.