Mumps virus is a common human pathogen that frequently invades the central nervous system (CNS). Strains of mumps virus differ in their cytopathogenicity (the degree of cytopathology that they cause in vitro) and their neurovirulence (the ability to invade the CNS and infect neurons) and there appears to be a correlation between the in vitro and in vivo biological effects. The molecular basis for these strain-dependent differences is not known and is the focus of the proposed experiments. Preliminary evidence suggests that the strain-dependent differences in cytopathogenicity and neurovirulence result, at least in part, from variation in the structure of the viral HN glycoprotein which mediates virion binding to host cells. The proposed experiments are designed to characterize the structure of the HN glycoprotein and to identify the functional domains that contribute to mumps virus cytopathogenicity and neurovirulence. Specifically, three different selection protocols will be used to isolate mumps virus variants that differ from the parental mumps virus strain by only minor alterations in the structure of the HN glycoprotein. The structural alterations will be defined at the level of the glycoprotein's amino acid sequence for those mumps virus variants that differ from the parental mumps virus strain in vitro and in vivo biological effects; in this way, the changes in primary structure that result in a modification in glycoprotein function and in virus virulence will be identified. Finally, an attempt will be made to generate polyclonal antibodies against putative functional domains of the HN glycoprotein by using as immunogens synthetic peptides with sequence homology to selected regions of the intact glycoprotein. Anti-peptide antibodies that recognize the HN glycoprotein in its native configuration will be tested for activity in in vitro functional assays and for a protective effect in the newborn hamster model of mumps meningoencephalitis. It is anticipated that the results of these studies will provide insight into the structure of the functional domains of the HN glycoprotein and will contribute to the understanding of the pathogenesis of mumps virus infection of the CNS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS023528-01
Application #
3407139
Study Section
Virology Study Section (VR)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Waxham, M N; Aronowski, J (1988) Identification of amino acids involved in the sialidase activity of the mumps virus hemagglutinin-neuraminadase protein. Virology 167:226-32
Waxham, M N; Aronowski, J; Server, A C et al. (1988) Sequence determination of the mumps virus HN gene. Virology 164:318-25
Waxham, M N; Server, A C; Goodman, H M et al. (1987) Cloning and sequencing of the mumps virus fusion protein gene. Virology 159:381-8