# CELLULAR GENE PRODUCT MODULATES FLAVIVIRUS RNA SYNTHESIS

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 1993 · $126,446

## Abstract

Many flaviviruses regularly cause significant human morbidity and
mortality.  Flavivirus-induced disease ranges from a mild febrile illness
to hepatitis, hemorrhagic syndromes, and encephalitis.  Vaccines are not
available for most flaviviruses.  Dengue virus, which can cause severe
hemorrhagic disease is spreading northward from the Caribbean basin as the
range of the mosquito vectors is extended by global warming.

We propose a research project aimed at defining the cis-acting sequences
and secondary structure elements of the flavivirus genome.  Such signals
are essential for regulating the replication, transcription and packaging
steps of the virus life cycle.  Through comparison of the 3 and 5'
sequences of a number of flaviviruses, nine short conserved sequences in
the 3' noncoding region and three short conserved sequences in the 5'
noncoding region have been identified.  Further, terminal secondary
structures have been found at both the 3' and 5' ends of the genome, but
the two structures differ markedly.  The sizes and shapes of these terminal
structures are conserved in the absence of sequence conservation in their
stem regions.  The conserved sequence elements present within the secondary
structures are located in loop regions.  To date none of these possible
cis-acting elements have been functionally tested.

Host factors have been identified as essential components of several RNA
virus replication complexes.  The involvement of at least one cellular
protein in flavivirus RNA replication is strongly suggested by the
existence of a flavivirus-specific resistance gene in mice.  Cells from
resistant animals are fully infectible, but synthesize flavivirus genomic
RNA inefficiently and preferentially amplify viral DI RNAs.  Experiments
are proposed to utilize small synthetic viral RNAs to search for high
affinity binding cell proteins by gel-shift and UV-induced cross-linking
assays.  Probes representing the 3' and 5' termini of WNV
plus-and-minus-strand RNAs will be tested.  Comparison of host factors
obtained from congenic resistant and susceptible mouse cells should allow
identification of the resistance gene product.  Host factors of interest
will be sequenced directly or cloned into lambda-gt11.  Clones will be
screened with host factor-specific antibody and selected clones sequenced.
Host factor binding sites on the viral RNA will be mapped.

## Key facts

- **NIH application ID:** 3127885
- **Project number:** 2R01AI018382-09A2
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **SAM.gov UEI:** MNS7B9CVKDN7
- **Principal Investigator:** Margo A Brinton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $126,446
- **Award type:** 2
- **Project period:** 1983-07-31 → 1996-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127885

## Citation

> US National Institutes of Health, RePORTER application 3127885, CELLULAR GENE PRODUCT MODULATES FLAVIVIRUS RNA SYNTHESIS (2R01AI018382-09A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127885. Licensed CC0.

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