# REPLICATION OF NEGATIVE STRAND RNA VIRUSES

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 1988 · $116,801

## Abstract

The genome of vesicular stomatitis virus is negative-stranded, nonsegmented
RNA (MW 4 million).  Complexed with the viral nucleoprotein N, it serves as
a template for two coupled pathways of RNA synthesis:  Transcription (the
sequential synthesis of a 47 base leader and five capped, methylated, and
polyadenylated monocistronic mRNAs) and Replication (the synthesis of
genomic-length positive- and negative-stranded RNAs which are complexed
with N protein).

The mechanisms governing the transcriptive and replicative pathways and
their coupled regulation are not fully understood.  The viral proteins L,
NS and N are multifunctional and involved in both pathways.  However, the
roles of these proteins are not known.  Transcriptive functions to be
assigned include: 1) polymerase, 2) polyadenylase, 3) guanylyltransferase,
4) guanine-7-methyltransferase, 5) nucleoside 2'-methyltransferase, 6)
putative processing endonuclease.  Replicative functions include
antitermination, nucleocapsid assembly, and negative strand synthesis.

The long-range goal of this research program is to assign transcriptive and
replicative functions to the viral proteins, and to determine how the
proteins and activities interact to promote and modulate the two pathways
of RNA synthesis.  The concept is based on the use of ts mutants with
lesions affecting transcription and replication as sources of altered L,
NS, and N proteins, the functional consequences of which will be determined
by the following experimental approaches: 1) Transcription defects will be
identified through analyses of the RNA products synthesized in
mutant-directed in vitro transcription reactions for aberrant capping,
methylation, polyadenylation, and processing-punctuation; 2) Replication
defects affecting nucleocapsid assembly and genomic-length RNA synthesis
will be analyzed in vivo with the aid of chimeric T particles coinfected
with mutant and wild-type standard virus; 3) An in vitro replication system
will be established for refined functional analyses of mutant proteins; 4)
The functional significance of NS phosphorylation will be explored through
coordinated functional and structural analyses of mutant and wildtype
variant NS proteins.

The significance of these studies arises from the striking similarity of
the salient features of VSV RNA synthesis to that of other members of the
nonsegmented negative-strand RNA virus group which are pathogenic to man.

## Key facts

- **NIH application ID:** 3125492
- **Project number:** 3R01AI013574-11S1
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **SAM.gov UEI:** H1HYA8Z1NTM5
- **Principal Investigator:** JUDITH A LESNAW
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $116,801
- **Award type:** 3
- **Project period:** 1978-06-01 → 1988-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125492

## Citation

> US National Institutes of Health, RePORTER application 3125492, REPLICATION OF NEGATIVE STRAND RNA VIRUSES (3R01AI013574-11S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125492. Licensed CC0.

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