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Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
Published on: June 16, 2011
Mapping antigenic diversity and strain specificity of mumps virus: a bioinformatics approach
Urmila Kulkarni-Kale1, Janaki Ojha, G Sunitha Manjari
1Bioinformatics Centre, University of Pune, Pune 411007, India. urmila@bioinfo.ernet.in
Abstract:
Mumps is an acute infectious disease caused by mumps virus, a member of the family Paramyxoviridae. With the implementation of vaccination programs, mumps infection is under control. However, due to resurgence of mumps epidemics, there is a renewed interest in understanding the antigenic diversity of mumps virus. Hemagglutinin-neuraminidase (HN) is the major surface antigen and is known to elicit neutralizing antibodies. Mutational analysis of HN of wild-type and vaccine strains revealed that the hypervariable positions are distributed over the entire length with no detectable pattern. In the absence of experimentally derived 3D structure data, the structure of HN protein of mumps virus was predicted using homology modeling. Mutations mapped on the predicted structures were found to cluster on one of the surfaces. A predicted conformational epitope encompasses experimentally characterized epitopes suggesting that it is a major site for neutralization. These analyses provide rationale for strain specificity, antigenic diversity and varying efficacy of mumps vaccines.
Insights
Mumps virus's surface protein, Hemagglutinin-neuraminidase (HN), shows significant antigenic diversity. Understanding its structure and mutations helps explain vaccine efficacy and mumps resurgence.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Mumps is an acute viral infection caused by the mumps virus (family Paramyxoviridae).
- Vaccination has controlled mumps, but recent epidemics highlight the need to understand viral antigenic diversity.
- The Hemagglutinin-neuraminidase (HN) protein is a key surface antigen responsible for eliciting neutralizing antibodies.
Purpose of the Study:
- To investigate the antigenic diversity of the mumps virus HN protein.
- To analyze mutations in wild-type and vaccine strains of the HN protein.
- To predict the 3D structure of the HN protein and map mutations onto it.
Main Methods:
- Mutational analysis of HN from wild-type and vaccine mumps virus strains.
- Homology modeling to predict the 3D structure of the HN protein in the absence of experimental data.
- Mapping of identified mutations onto the predicted protein structure.
Main Results:
- Hypervariable positions in the HN protein were found distributed throughout its length without a clear pattern.
- Predicted 3D structures revealed that mutations cluster on a specific surface of the HN protein.
- A predicted conformational epitope, encompassing known epitopes, was identified as a likely major neutralization site.
Conclusions:
- The study provides structural insights into the antigenic diversity of the mumps virus HN protein.
- Findings offer a rationale for observed strain specificity and varying efficacy of mumps vaccines.
- Understanding HN structure and mutation patterns is crucial for addressing mumps resurgence and improving vaccine strategies.
