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Functional Analysis of the Halastavi árva Virus (HalV) Internal Ribosome Entry Site.
Subash Chapagain1, Lauren F Woodburn1, Natalie C J Strynadka1
1Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Viruses
|May 27, 2026
Summary
The Halastavi árva virus (HalV) internal ribosome entry site (IRES) is a minimalist RNA structure that initiates translation without protein factors. Its activity depends on specific cellular conditions, being enhanced by viral infection.
Area of Science:
- Molecular Biology
- Virology
- RNA Biology
Background:
- Viral internal ribosome entry sites (IRESs) enable cap-independent translation, hijacking host machinery.
- Type 6 IRESs are streamlined, using RNA structures for factorless translation initiation.
- The Halastavi árva virus (HalV) IRES is a minimalistic subclass, lacking 40S subunit binding domains and recruiting 80S ribosomes.
Purpose of the Study:
- To investigate the cellular conditions supporting HalV IRES translation.
- To understand the mechanism of HalV IRES-mediated translation initiation.
Main Methods:
- Assessing HalV IRES activity in various cell lysates and cell lines (Sf21, Drosophila S2, RRL, wheat germ).
- Evaluating the impact of cellular stress (heat shock, serum starvation) and viral infection on HalV IRES activity.
- Testing HalV IRES function in a heterologous viral replicon system.
Main Results:
- HalV IRES is active in insect cell lysates and Drosophila S2 cells, but inactive in mammalian RRL and wheat germ extract.
- Heat shock and serum starvation inhibit HalV IRES activity.
- Viral infection significantly enhances HalV IRES-mediated translation.
- The HalV IRES supports viral translation and replication in a heterologous system.
Conclusions:
- HalV IRES activity is highly dependent on specific cellular environments and host factors.
- Minimalist IRESs like HalV IRES require precise cellular conditions for ribosome recruitment and translation initiation.
- These findings provide insights into the context-specific regulation of factorless translation by minimalist viral IRES elements.
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