The discovery of Orsay virus, the first natural virus of C. elegans, has allowed us to better understand potentially evolutionary conserved virus-host interaction mechanisms. We developed a forward genetic screen to identify genes critical for Orsay virus infection. Specifically, we used a transcriptional GFP fusion reporter of a virus-responsive gene to isolate mutants unable to turn on GFP, and then used qRT-PCR to quantify defects in Orsay virus replication. Using this strategy, we previously identified multiple genes critical for Orsay infection, including
sid-3,
viro-2,
drl-1,
nck-1 and
hipr-1. Here, we focused on an independent mutant not previously characterized that had a <1000-fold reduction in orsay virus RNA relative to the unmutagenized control strain. Using a F2 bulk segregant strategy, an early stop codon mutation in the
alg-1 gene was identified as a candidate gene responsible for the mutant phenotype. The genetic rescue of such mutant with a fosmid containing the
alg-1 gene was sufficient to recover the susceptibility of the mutant to the parental levels of infection. Consistent with these results, an independent mutant allele in the
alg-1 gene,
gk214, showed <1000-fold reduction in Orsay virus RNA compared to the wild type. The isolated
alg-1 mutant was able to induce GFP in response to the intracellular pathogen Nematocida parisii, suggesting that
alg-1 mutation leads to a virus specific phenotype.
alg-1 gene encodes an argonaute-like protein component of the microRNA pathway in C. elegans that influences lifespan, regulates gene expression, and is suggested to physically interact with RNA. Our results suggest that C. elegans
alg-1 gene plays an important role in promoting orsay virus infection. The observed pro-viral activity of C. elegans
alg-1 contrasts with the reported antiviral activity of its human ortholog AGO2.