Sequence variation and biological activity of rubella virus isolates

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Rubella virus E1 glycoprotein mediates haemagglutination.
• Previous studies identified an epitope (EP1) on E1 that binds neutralizing monoclonal antibodies.
• Variations in rubella virus isolates affect haemagglutination avidity and plaque size.

Purpose of the Study:

• To characterize rubella virus isolates with differing haemagglutination avidity.
• To investigate the role of specific E1 glycoprotein mutations in rubella virus haemagglutination.
• To correlate viral characteristics with infectivity and antibody binding.

Main Methods:

• Characterization of rubella virus isolates based on haemagglutination (HA) titre and plaque size.
• Amino acid sequencing of the E1 glycoprotein, focusing on immunogenic regions.
• Analysis of HA titre reduction at low pH (pH 6.0).
• Assessment of binding affinity for neutralizing monoclonal antibodies.

Main Results:

• One rubella virus isolate showed a significant reduction in HA titre at pH 6.0.
• This isolate had an isoleucine substitution for threonine at E1 residue 280 (T280I).
• Residue 280 is located within the EP1 epitope, known to bind HA inhibiting (HA1) monoclonal antibodies.
• No sequence variations in the E1 immunogenic region correlated with observed differences in plaque size.
• No correlation was found between viral infectivity and the binding affinity of neutralizing monoclonal antibodies.

Conclusions:

• The T280I substitution in the rubella virus E1 glycoprotein significantly impacts haemagglutination avidity.
• E1 residue 280 is critical for maintaining normal haemagglutination function.
• Viral infectivity and antibody neutralization are not directly correlated with E1 binding affinity in the studied isolates.