# TRANSLATIONAL CONTROL MECHANISMS

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT STORRS · 1988 · $162,441

## Abstract

The overall aim of this research program is to define the mechanism by
which cellular mRNA translation is inhibited in vesicular stomatitis virus
(VSV) and mengovirus infected L cells.  Studies on the defect in the
process of initiation of protein synthesis will be carried out.  Both
initiation factor eIF-2 and a fraction containing a mixture of eIF-4B and
eIF-4F are required for restoring protein synthesis activity in lysates
from VSV infected cells.  It is proposed that the catalytic function of
eIF-2 is altered after infection.  To test this hypothesis the state of
phosphorylation of eIF-2 in infected cells and in extracts from infected
cells will be determined.  The ability of the purified eIF-2.eIF-2B complex
to rescue cellular mRNA translation will also be tested.  The fraction
containing eIF-4B and eIF-4F will be fractionated and the isolated
components tested individually to ascertain which is the actual rescue
factor.

The two regions of the VSV genome which must be transcribed for the
inhibition of cellular protein synthesis will be further characterized
using RNA-DNA hybridization techniques with recombinant plasmid DNAs
containing cDNAs to VSV mRNAs and the exact 3' end of the virus genome as
probes.  Temperature sensitive VSV mutants will be screened at the
permissive and restrictive temperatures to determine if there is a
correlation between the presence of the transcripts and the inhibition of
protein synthesis.

Cell killing and protein synthesis inhibition are strongly related.  The
less cytopathic the virus stock, the less severe the immediate inhibition
of protein synthesis.  VSV stocks will be fractionated using sucrose
gradient analysis in an attempt to isolate the putative protein synthesis
inhibitory particles.  These particles will be tested for their ability to
kill cells.

The S-l00 fraction of mouse L cells will be fractionated by conventional
means in order to characterize the factor necessary for restoring protein
synthesis activity in lysates from mengovirus infected cells.

VSV and mengovirus are prototypes of such extremely virulent viruses as
rabies and poliovirus, respectively.  Therefore, it is hoped that these
studies will help us understand the basis for the cytopathogenicity of
certain virulent viruses that affect mankind.

## Key facts

- **NIH application ID:** 3126479
- **Project number:** 5R01AI015898-18
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **SAM.gov UEI:** WNTPS995QBM7
- **Principal Investigator:** JEAN M LUCAS-LENARD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $162,441
- **Award type:** 5
- **Project period:** 1979-09-01 → 1990-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126479

## Citation

> US National Institutes of Health, RePORTER application 3126479, TRANSLATIONAL CONTROL MECHANISMS (5R01AI015898-18). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3126479. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*