Immune metabolites and RNA modifications in antiviral defense

Viruses reshape host metabolism and RNA biology to replicate and evade immunity. Our lab studies how immune metabolites and RNA modifications function as both weapons and vulnerabilities in this conflict. We focus on the antiviral enzyme viperin, its product ddhC, and viral N7-methyltransferases (N7-MTases) that induce internal m7G RNA modification. Our long-term goal is to harness these pathways as broad-spectrum biomarkers and targets for antiviral strategies.

Many RNA viruses encode N7-methyltransferases (N7-MTases) to cap their RNAs and ensure efficient gene expression. Our work has revealed that the SARS-CoV-2 N7-MTase NSP14 has an additional activity: it induces widespread internal m7G modifications in host mRNAs.

These internal N7-methylguanosine (m7G) marks are emerging as an important layer of RNA regulation during infection.

We are investigating:

• How NSP14 and related viral N7-MTases trigger internal m7G on host RNAs
   
• Which host factors control the extent and specificity of internal m7G modification
   
• How aberrant m7G affects RNA processing, splicing, nuclear export, and antiviral responses
   
• Whether dysregulated m7G contributes to longer-term disease phenotypes, including inflammation and cancer

Viperin (RSAD2) is an interferon-induced antiviral protein that converts CTP into the unusual nucleotide ddhCTP (deoxy-3′,4′-didehydro-cytidine triphosphate), which is further processed into the nucleoside ddhC. This pathway directly limits viral replication and rewires host metabolism and stress responses. We are defining how the viperin–ddhC axis operates across different viral infections and cell types:

• Mechanism and regulation of ddhC production during acute viral infection  

• How ddhC and related metabolites alter virus–host interactions and antiviral responses 

• The potential of ddhCTP-derived nucleoside analogs as leads for new antiviral or immunomodulatory agents

• Evaluating ddhC as a broad-spectrum diagnostic marker that can complement or substitute virus-specific assays