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Updated: Jul 4, 2025
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Minor intron-containing genes as an ancient backbone for viral infection?
Stefan Wuchty1,2,3,4, Alisa K White5, Anouk M Olthof5
1Department of Computer Science, University of Miami, Coral Gables, FL 33146, USA.
Abstract:
Minor intron-containing genes (MIGs) account for <2% of all human protein-coding genes and are uniquely dependent on the minor spliceosome for proper excision. Despite their low numbers, we surprisingly found a significant enrichment of MIG-encoded proteins (MIG-Ps) in protein-protein interactomes and host factors of positive-sense RNA viruses, including SARS-CoV-1, SARS-CoV-2, MERS coronavirus, and Zika virus. Similarly, we observed a significant enrichment of MIG-Ps in the interactomes and sets of host factors of negative-sense RNA viruses such as Ebola virus, influenza A virus, and the retrovirus HIV-1. We also found an enrichment of MIG-Ps in double-stranded DNA viruses such as Epstein-Barr virus, human papillomavirus, and herpes simplex viruses. In general, MIG-Ps were highly connected and placed in central positions in a network of human-host protein interactions. Moreover, MIG-Ps that interact with viral proteins were enriched with essential genes. We also provide evidence that viral proteins interact with ancestral MIGs that date back to unicellular organisms and are mainly involved in basic cellular functions such as cell cycle, cell division, and signal transduction. Our results suggest that MIG-Ps form a stable, evolutionarily conserved backbone that viruses putatively tap to invade and propagate in human host cells.
Insights
Minor intron-containing genes (MIGs) are crucial for viral infection. These evolutionarily conserved proteins form a backbone that viruses exploit to invade and replicate within host cells.
Area of Science:
- Molecular Biology
- Virology
- Genetics
Background:
- Minor intron-containing genes (MIGs) constitute a small fraction of human protein-coding genes (<2%).
- MIGs rely on the minor spliceosome for accurate RNA processing.
- MIG-encoded proteins (MIG-Ps) are surprisingly implicated in host-pathogen interactions.
Purpose of the Study:
- To investigate the role of MIG-Ps in viral infections.
- To identify viral interactions with MIG-Ps across diverse virus families.
- To understand the evolutionary conservation and functional significance of MIG-Ps in host-virus networks.
Main Methods:
- Analysis of protein-protein interaction databases.
- Comparative analysis of host factors for various RNA and DNA viruses.
- Network analysis to assess the connectivity and centrality of MIG-Ps.
- Phylogenetic analysis of MIGs interacting with viral proteins.
Main Results:
- MIG-Ps are significantly enriched in the interactomes and host factor sets of positive-sense RNA viruses (e.g., SARS-CoV-2), negative-sense RNA viruses (e.g., Ebola, HIV-1), and double-stranded DNA viruses (e.g., HSV).
- MIG-Ps occupy central positions in human-host protein interaction networks and are highly connected.
- Viral proteins interact with evolutionarily ancient MIGs involved in fundamental cellular processes like cell cycle and signal transduction.
- MIG-Ps interacting with viral proteins are enriched in essential genes.
Conclusions:
- MIG-Ps represent a conserved, essential host factor utilized by a broad spectrum of viruses.
- Viruses exploit this stable, evolutionarily conserved MIG-P backbone for invasion and propagation.
- Understanding MIG-P-virus interactions offers potential targets for antiviral strategies.
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