Researchers at the Indian Institute of Science (IISc) in Bengaluru have decoded the virus hijack mechanism that allows the encephalomyocarditis virus (EMCV) to seize control of a host cell's protein-making machinery, a discovery that could open new pathways for antiviral drug design. Published in the peer-reviewed journal eLife, the study used cryo-electron microscopy (cryo-EM) to capture, for the first time, the exact molecular choreography by which the virus commandeers host ribosomes to manufacture its own proteins.
EMCV is a rodent-borne virus known to cause heart and brain inflammation, reproductive complications, and neurological disorders in a range of mammals. Like most viruses, it cannot produce proteins on its own and depends entirely on the machinery of the cells it infects. To do this, EMCV relies on a specialised stretch of genetic material called an Internal Ribosomal Entry Site (IRES), a structure that was first identified in EMCV and the poliovirus more than three decades ago. Until now, scientists had a broad sense that the IRES hijacked ribosomes, but the fine biochemical detail of how it did so had remained elusive.
Why Did the Structure Remain a Mystery for So Long?
According to Tanweer Hussain, Associate Professor at Indian Institute of Science’s Department of Developmental Biology and Genetics, nothing was known about the details of how the virus captures the host ribosome beyond the identity of the translational factors involved. The research team designed a specially engineered bait protein to fish out the entire IRES complex intact from infected cell lysate, including the 40S ribosomal subunit, the initiator tRNA, and the eIF2 translation-initiation factor complex.
Early purification attempts showed promise, but many subsequent rounds failed to yield usable material, forcing the team to repeatedly refine their approach before cryo-EM grids finally produced particles clear enough for detailed structural analysis.
What Did the Cryo-EM Images Reveal About Ribosome Hijacking?
The images revealed something researchers had not observed in any other virus studied so far. The EMCV IRES makes direct contact with both the host's 40S ribosomal subunit and the initiator tRNA, rather than relying solely on the usual set of translation factors that host cells use for their own protein synthesis. This direct-contact strategy effectively lets the virus shortcut the host's normal checkpoints, redirecting the cell's ribosomes toward manufacturing viral rather than cellular proteins.
The finding matters well beyond EMCV. The poliovirus and several other pathogens are believed to use a structurally related IRES-driven strategy, meaning the mechanism mapped by the IISc team could serve as a template for understanding, and eventually disrupting, ribosome hijacking across an entire family of viruses.
Could This Lead to New Antiviral Therapies?
Because the IRES is essential to viral replication and structurally distinct from anything in normal human protein synthesis, it represents an attractive and relatively virus-specific drug target. A therapy designed to block the IRES from docking onto the ribosome could, in principle, stop the virus from hijacking host machinery altogether, without disrupting the cell's own protein production. Researchers caution that translating a structural discovery into an approved drug is a long road, involving years of further validation, but the level of molecular detail now available gives drug designers a genuine starting point that did not exist before.
IISc's cryo-EM facility has increasingly become a hub for this kind of structural virology work, building on the institute's earlier research into how viruses such as SARS-CoV-2 and HIV interact with host cells. The EMCV study adds to a growing body of Indian research demonstrating that world-class structural biology can be done domestically, reducing reliance on international collaborations for foundational virology work.
For a country that has repeatedly grappled with viral outbreaks, from COVID-19 to recurring dengue and Nipah scares, home-grown insight into the basic mechanics of how viruses operate carries significance that extends past any single pathogen. The IISc findings offer both a scientific milestone and a practical foundation for future antiviral research that could, over time, reduce India's dependence on imported therapeutics during public health emergencies.
Sign in to leave a comment.