RNA-based antiviral immunity

Abstract

In eukaryotic RNA-based antiviral immunity, viral double-stranded RNA is recognized as a pathogen-associated molecular pattern and processed into small interfering RNAs (siRNAs) by the host ribonuclease Dicer. After amplification by host RNA-dependent RNA polymerases in some cases, these virus-derived siRNAs guide specific antiviral immunity through RNA interference and related RNA silencing effector mechanisms. Here, I review recent studies on the features of viral siRNAs and other virus-derived small RNAs from virus-infected fungi, plants, insects, nematodes and vertebrates and discuss the innate and adaptive properties of RNA-based antiviral immunity.

The 21-Nucleotide, but Not 22-Nucleotide, Viral Secondary Small Interfering RNAs Direct Potent Antiviral Defense by Two Cooperative Argonautes inArabidopsis thaliana

“…In Arabidopsis, hypomorphic ago1 and null ago7 mutants accumulate higher levels of viral RNA, and AGO1, AGO2, and AGO5 bind to viral siRNAs in the infected cells, suggesting an antiviral role for these AGOs (Morel et al, 2002;Zhang et al, 2006;Qu et al, 2008;Takeda et al, 2008;Azevedo et al, 2010). Lossof-function mutation in several additional Arabidopsis genes, including RDR6, SGS3, and HEN1, also leads to enhanced disease susceptibility to RNA viruses (Mourrain et al, 2000;Boutet et al, 2003;Ding and Voinnet, 2007;Ding, 2010;Llave, 2010;Qu, 2010).…”

“…Less is known about the downstream components in RNAbased antiviral immunity (Ding, 2010;Llave, 2010;Qu, 2010). The function of ARGONAUTE (AGO) proteins is clearly essential since genetic inactivation of a single AGO without altering dicing enhances virus susceptibility in fungal, insect, nematode, and plant hosts (Li et al, 2002;Morel et al, 2002;Lu et al, 2005Lu et al, , 2009Schott et al, 2005;Wilkins et al, 2005;van Rij et al, 2006;Zambon et al, 2006;Qu et al, 2008;Sun et al, 2009).…”

“…Viral siRNAs detected in Arabidopsis thaliana plants infected with positive-strand RNA viruses are predominantly 21 nucleotides in length made by DCL4, which also produces endogenous trans-acting siRNAs (ta-siRNAs) and siRNAs targeting transgenes (Ding and Voinnet, 2007;Voinnet, 2008). The 22-nucleotide viral siRNAs produced by DCL2 in the presence of DCL4 often constitute <20% of the total viral small RNA population (Ding, 2010;Llave, 2010). However, elimination of both DCL4 and DCL2 is required to dramatically increase disease susceptibility to distinct RNA viruses or to restore pathogenicity of mutant viruses defective in silencing suppression Deleris et al, 2006;Diaz-Pendon et al, 2007), indicating that effective virus resistance is initiated by either DCL4 or DCL2.…”

“…RNA silencing provides protection against diverse RNA viruses in many eukaryotic organisms (Ding, 2010;Llave, 2010;Qu, 2010). In this antiviral defense, small interfering RNAs (siRNAs) are processed from a viral RNA precursor and used to guide specific silencing of the cognate viral RNAs in an Argonaute-containing effector complex.…”

Silencing suppressors: viral weapons for countering host cell defenses

“…It was first discovered in plants that RNAi provides an antiviral mechanism by which viral dsRNAs are cleaved by the ribonuclease Dicer to generate viral siRNAs. These siRNAs are then incorporated into the RNA-induced silencing complex (RISC) and direct RISC activity to messenger RNAs (mRNAs) in a sequence-specific manner (Ding and Voinnet, 2007;Ding, 2010;Olivieri et al, 2010;Reyes et al, 2011). Complementary sequences in the viral mRNA can be targeted by the viral siRNAs for endonucleic cleavage or translational inhibition, which represses viral replication.…”