# CONTROL OF TRANSLATION IN POLIOVIRUS INFECTED CELLS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 1993 · $256,847

## Abstract

The aim of this research is to understand the mechanism by which poliovirus
infection causes a specific inhibition of host cell protein synthesis,
while production of viral proteins proceeds efficiently.  Extracts derived
from infected cells are unable to translate capped mRNAs in vitro, although
they are capable of translating viral RNA, which is not capped.  This
restriction against translation of capped mRNAs is because of a virus-
induced inactivation of a protein synthesis initiation factor (eIF-4F),
which is required for the binding of capped mRNAs to the ribosome.  The
initiation factor contains a small polypeptide subunit which binds cap
structures, and a large subunit, which becomes cleaved shortly after
poliovirus infection.  Cleavage of this large subunit presumably
inactivates the function of the factor.

The viral gene responsible for cleavage of the initiation factor subunit is
a gene that codes for a protease.  This protease, however, does not
catalyze the cleavage directly, but rather it activates a latent, cellular
protease which then cleaves the initiation factor.  Studies proposed in
this application will identify the latent, cellular protease and define the
biochemical mechanism of the protease cascade.

An additional objective is to determine how poliovirus RNA binds to
ribosomes and initiates translation in the absence of a capped 5' end and
therefore without the aid of the cap recognition system.  Experiments are
proposed to identify the sequences and/or structures in the 5' noncoding
region of the viral RNA that are required for cap-independent ribosome
binding, and also to isolate trans-acting factors which interact with this
region.

These studies will contribute to our understanding of how protein synthesis
is regulated in infected cells, in ways that determine virus-host cell
interactions which likely contribute to neurovirulence and host range
properties of this virus.

## Key facts

- **NIH application ID:** 3125180
- **Project number:** 5R01AI012387-20
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **SAM.gov UEI:** MJC5FCYQTPE6
- **Principal Investigator:** Ellie R. Ehrenfeld
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $256,847
- **Award type:** 5
- **Project period:** 1975-05-01 → 1995-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125180

## Citation

> US National Institutes of Health, RePORTER application 3125180, CONTROL OF TRANSLATION IN POLIOVIRUS INFECTED CELLS (5R01AI012387-20). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125180. Licensed CC0.

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