# REGULATION OF ALPHAVIRUS TRANSCRIPTION

> **NIH NIH R01** · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · 1991 · $187,347

## Abstract

Alphaviruses are of general interest because they produce disease in a
variety of animals, including humans, and because they replicate in
invertebrates as well as vertebrates.  Their broad replicative potential
is essential for their transmission and thus for the spread of their
associated diseases.  Successful synthesis of many infectious progeny
starts with the translation and copying of the infecting genomic into a
complementary, or negative-strand, RNA template.  Understanding the
mechanism of alphavirus RNA synthesis and translation and of the
regulation of negative strand transcription will contribute to our
understanding of how cells function and regulate the expression of their
genetic information.  Furthermore, alphaviruses cause persistent
infection in mosquitos and must have evolved a mechanism that allows
viral replication but prevents Emg infected mosquitos which are their
reservoir in nature.  Therefore, our long range goal is to develop
experimental methods that allow us to investigate the nature of the
molecular mechanism by which alphaviruses, and most probably also rubella
virus, create a viral replication complex and regulate their rate of
transcription.  Our three aims for the next granting period are: 1. To
purify and characterize alphavirus replication complexes which will be
isolated from cells infected with either parental virus,
conditionally-lethal mutants, or defective-interfering particles
containing DI RNA that is much shorter than genome RNA and to develop
conditions that permit in vitro replication of exogeneous templates. 2.
To identify host cell components that are associated with alphavirus
replication complexes and determine their role in viral replication. 3.
To define the functions of viral nonstructural proteins in negative
strand synthesis and in the temporal cessation of negative strand
synthesis.  Using the infectious Sindbis clone, we will map the mutations
in ts4 which prevent negative strand synthesis and in ts17 and ts133
which also possess the ability to synthesize negative strands late in
infection, i.e., the 24R phenotype, and test the hypothesis that nsP2, in
addition to nsP4, plays a role in the temporal cessation of negative
strand synthesis.  Using site-directed mutagenesis, we will determine
which amino acid alterations in nsp4, other than the one in ts24 and 24R,
allow the continuation of negative strand synthesis late in infection,
i.e., give the 24R phenotype and we will define amino acids changes in
nsPI, other than the one in ts11 , that makes negative strand synthesis
temperature-sensitive and probe further the role of nsP 1 in negative
strand synthesis.

## Key facts

- **NIH application ID:** 3126021
- **Project number:** 2R01AI015123-14
- **Recipient organization:** UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
- **SAM.gov UEI:** M9ACC5DQCNL6
- **Principal Investigator:** DOROTHEA L SAWICKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $187,347
- **Award type:** 2
- **Project period:** 1978-09-01 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126021

## Citation

> US National Institutes of Health, RePORTER application 3126021, REGULATION OF ALPHAVIRUS TRANSCRIPTION (2R01AI015123-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126021. Licensed CC0.

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