IISc researchers decode how virus hijacks host protein machinery

According to the researchers, viruses lack their own molecular machinery needed for protein synthesis. Instead, they hijack the host’s protein machinery. | Photo credit: Getty Images

Scientists at the Indian Institute of Science (IISc) in Bengaluru have decoded how the encephalomyocarditis virus (EMCV) hijacks the host’s protein synthesis machinery.

EMCV is an animal virus transmitted by rodents that causes inflammation of the heart and brain, reproductive problems and neurological disorders in many mammals.

According to scientists, viruses lack their own molecular machinery needed for protein synthesis. Instead, they hijack the host’s protein machinery, specifically ribosomes and translation factors.

Viral propagation

“This process is essential for viral multiplication and infection. Viruses have RNA genomes or mRNAs containing structured regions called Internal Ribosomal Entry Sites (IRES) that help capture the host ribosome to translate viral genes while host gene translation is blocked,” it said.

In a new study published in eLife , researchers used cryo-electron microscopy (cryo-EM) to decode how the EMCV IRES hijacks the host’s protein synthesis machinery.

IISc said that targeting the IRES could open up new therapeutic strategies against this virus and similar viruses – such as poliovirus – that use the same mechanism.

IRESs were originally discovered more than a decade ago in EMCV and poliovirus. However, their structure and the specific mechanisms by which they act have remained elusive.

“Nothing was known about the details of how the virus captures the host ribosome – other than the translation factors involved – and exactly how it does it biochemically,” said Tanweer Hussain, associate professor in the Department of Developmental Biology and Genetics (DBG), IISc and corresponding author.

Pulldown strategy

To address this gap, Deepakash Das, a PhD student in Professor Hussain’s lab and first author, designed a pull-down strategy using EMCV IRES-containing mRNA to isolate the EMCV IRES pre-initiation complex from rabbit reticulocyte (immature red blood cells) cell lysate. This pre-initiation complex is the assembly that the viral RNA forms with the host ribosome to capture it, marking the first step in the production of viral proteins.

Using a specially designed bait protein, the team fished out and captured the entire IRES complex intact, including various key components of translation initiation—the 40S ribosomal subunit, initiation tRNA, and the eIF2 (eukaryotic initiation factor 2) complex—from the cell lysate and then examined it using cryo-EM

“The first cleaning attempts went well – something of a beginner’s luck – but many subsequent rounds did not produce usable results. Cryo-EM grids often failed to provide enough particles for a reliable structure, but we persisted,” Professor Hussain said.

Finally, IISc said, the cryo-EM images showed that the EMCV IRES directly interacts with the 40S ribosomal unit and host initiator tRNA—a mechanism not previously used by other viruses—to hijack the host’s translation machinery.

Published – 23 Jul 2026 19:54 IST