bioRxiv Science⌕ Search

Biology subjects

Batachari, L. E.

Publications and source records attributed to Batachari, L. E..

2 recordsLinked to original sources
bioRxiv2026

Viral infection drives cell-intrinsic re-localization of the C. elegans immune-repressive STAT transcription factor STA-1

Detection of viral infection leads to both cell-intrinsic and cell-extrinsic responses. In mammals, cell-intrinsic detection of viral infection leads to cell-extrinsic activation of STAT (Signal Transduction and Activators of Transcription) proteins, a family of transcription factors that promote anti-viral defense. In the nematode C. elegans, STA-1/STAT is a negative regulator of anti-viral defense, but it is not known if it acts cell-intrinsically or cell-extrinsically and whether it has functional domains conserved with mammalian STATs. Here we show that C. elegans STA-1 protein disappears from nuclei of cells infected with the natural viral pathogen, Orsay virus, but remains nuclear in uninfected cells, indicating a cell-intrinsic site of action. During viral infection, STA-1 forms cytoplasmic puncta that interact with the RNA viral sensor DRH-1, suggesting that DRH-1 helps restrain this immune-repressive factor. STA-1 overexpression causes increased susceptibility to viral infection, in a manner dependent on conserved residues important for DNA binding, nuclear localization and phosphorylation. Structural predictions indicate that STA-1 is most similar to STAT5 proteins in mammals, which have known immune-repressive roles. Our transcriptomic analysis demonstrates that C. elegans STA-1 regulates a general anti-pathogen program, including genes upregulated later during viral infection. Altogether, our findings provide insight into conserved and distinct features of STA-1 in C. elegans, indicating an ancient role for cell-intrinsic, immune-repressive STATs. Author SummaryAll living organisms must detect viral infections and mount a defense to survive. One major antiviral defense pathway in mammals is the interferon response, which involves sensing viral infection in one cell, and delivering an interferon message to neighboring cells. These neighboring cells then turn on anti-viral defense gene expression using proteins called STAT transcription factors. We study anti-viral defense in the roundworm C. elegans, and in this study show that viral infected cells themselves use a STAT protein called STA-1, with perhaps a lesser role for STA-1 in neighboring cells, in contrast to mammals. We also extend on previous findings that STA-1 turns off anti-viral gene expression, and we analyze regions in the protein to demonstrate that STA-1 is bona fide transcription factor with an immune-repressive role. Structural prediction analysis of STA-1 indicates it is most similar to STAT5 in mammals, suggesting an ancient role for this protein as an immune-repressive factor acting directly in virally infected cells.

immunology↗
bioRxiv2024

C. elegans RIG-I-like receptor DRH-1 signals via CARDs to activate anti-viral immunity in intestinal cells

Upon sensing viral RNA, mammalian RIG-I-like receptors activate downstream signals using caspase activation and recruitment domains (CARDs), which ultimately promote transcriptional immune responses that have been well-studied. In contrast, the downstream signaling mechanisms for invertebrate RIG-I-like receptors are much less clear. For example, the Caenorhabditis elegans RIG-I-like receptor DRH-1 lacks annotated CARDs and upregulates the distinct output of RNA interference (RNAi). Here we found that, similar to mammal RIG-I-like receptors, DRH-1 signals through two tandem caspase activation and recruitment domains (2CARD) to induce a transcriptional immune response. Expression of DRH-1(2CARD) alone in the intestine was sufficient to induce immune gene expression, increase viral resistance, and promote thermotolerance, a phenotype previously associated with immune activation. We also found that DRH-1 is required in the intestine to induce immune gene expression, and we demonstrate subcellular colocalization of DRH-1 puncta with double-stranded RNA inside the cytoplasm of intestinal cells upon viral infection. Altogether, our results reveal mechanistic and spatial insights into anti-viral signaling in C. elegans, highlighting unexpected parallels in RIG-I-like receptor signaling between C. elegans and mammals. SignificanceViruses are ubiquitous pathogens that challenge diverse organisms, from bacteria to killer whales. While anti-viral defense has been well-studied in mammals, less is known about defense in invertebrates, including the roundworm Caenorhabditis elegans. Here we show that the C. elegans viral sensor DRH-1 shares similarities to a viral sensor in mammals called RIG-I. We find that DRH-1 has a signaling motif resembling the 2CARD motif, which is found in RIG-I and activates anti-viral immunity. We demonstrate that overexpression of DRH-1(2CARD) in C. elegans promotes resistance to viral infection, and that DRH-1 forms clusters inside intestinal cells during viral infection, similar to RIG-I in humans. Overall, these findings provide insights into C. elegans anti-viral immunity, highlighting similarities with mammalian anti-viral immunity.

immunology↗