# BIOSYNTHESIS OF PARAMYXOVIRUSES

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 1993 · $179,093

## Abstract

Paramyxoviruses are the most important cause of respiratory disease in
children.  The long-term objective is to develop means to prevent
respiratory disease caused by parainfluenza viruses.  To reach that
objective, the proposed research will focus on the roles of the
hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins during
infection using two parainfluenza virus 1 subtypes: Sendai virus (SV), a
natural pathogen of mice, and human parainfluenza type 1 (hPIV-1), an
important pathogen of children.  The strategy is to apply
structure/function analysis to each of these viral proteins as outlined
in the following specific aims.  Aim 1: We propose to definitively
establish a role of HN in virus fusion, structurally define the fusion
promoting domain and the nature of the fusion promoting function.  Aim 2:
Determine the structural correlates and the biological significance of
the neuraminidase activity of SV HN.  Aim 3: To prepare molecules of HN
and F that form crystals suitable for establishing the threedimensional
structure.

Aims 1 and 2 will use epitope mapping, sequence analysis and functional
characterization of neutralization escape mutants, ts mutants that fail
to make HN, and expression of cDNAs in conjunction with site-directed
mutagenesis to define the structural domains and biological significance
of the fusion promoting and neuraminidase functions of HN.  These methods
will be used to define the antigenic structure, critical amino acids, and
the extent and complexity of each domain.  Studies using ts mutants and
cDNA expression will examine the unresolved roles of the fusion promoting
and neuraminidase activities of HN in virus infection.  SV HN mutants
with enhanced neuraminidase activity and significantly increased growth
in embryonated eggs will be used to test the hypothesis that
neuraminidase activity in general is a determinant of virus infectivity,
pathogenesis and virulence.  Aim 3 will prepare F molecules with
potential for crystallization and X-ray analysis.  Requirements are (i)
removal of the hydrophobic membrane anchoring termini (tails) by
proteolysis, (ii) purification of tailless molecules by centrifugation
and chromatography, and (iii) retention of biological activity.
Antigen-MAb complexes will serve as an alternate method of
crystallization.

## Key facts

- **NIH application ID:** 3125066
- **Project number:** 2R01AI011949-18A1
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **SAM.gov UEI:** JL4JHE9SDRR3
- **Principal Investigator:** ALLEN PORTNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $179,093
- **Award type:** 2
- **Project period:** 1978-07-01 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125066

## Citation

> US National Institutes of Health, RePORTER application 3125066, BIOSYNTHESIS OF PARAMYXOVIRUSES (2R01AI011949-18A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125066. Licensed CC0.

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