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Interactions between the ectodomains of haemagglutinin and CD46 as a primary step in measles virus entry
P Devaux1, B Loveland, D Christiansen
1Immunité et Infections Virales, IVMC, CNRS-UCBL UMR 30, Lyon, France.
Abstract:
Recombinant soluble forms of the ectodomains of measles virus haemagglutinin (sH) and of its receptor CD46 (sCD46) were obtained as a purified disulphide-bonded sH homodimer with an apparent molecular mass of 160 kDa and a purified sCD46 monomer with an apparent molecular mass of 60 kDa, without detectable contamination with moesin. Purified sH bound to purified and immobilized sCD46 and this binding was specifically inhibited by sCD46 in solution. sCD46 bound to wild-type H expressed on the cell surface and inhibited measles virus binding to CD46-expressing cells. Binding of sCD46 to cell surface H was increased about twofold when measles virus fusion protein was coexpressed with H. sH bound to wild-type cell surface CD46 and inhibited measles virus binding onto CD46-expressing cells. sCD46 also inhibited virus infection. Thus, the direct interaction between the ectodomains of H and CD46 is likely to be the primary event in measles virus infection.
Insights
Measles virus haemagglutinin (H) and its receptor CD46 interact directly. This interaction is key for measles virus infection, as soluble forms of H and CD46 block viral binding and infection.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Measles virus infects humans via its haemagglutinin (H) protein binding to cellular receptors.
- CD46 is a known receptor for measles virus, mediating viral entry.
- Understanding the molecular interactions between H and CD46 is crucial for developing antiviral strategies.
Purpose of the Study:
- To investigate the direct interaction between the ectodomains of measles virus haemagglutinin (H) and its receptor CD46.
- To determine if this interaction is essential for measles virus binding and infection.
Main Methods:
- Production and purification of recombinant soluble H (sH) and soluble CD46 (sCD46).
- Assessing binding affinity between sH and immobilized sCD46 using biochemical assays.
- Evaluating the inhibitory effects of sCD46 on measles virus binding to cell-surface H and CD46-expressing cells.
- Measuring the impact of sCD46 on measles virus infection.
Main Results:
- Purified sH formed a homodimer and bound to purified sCD46.
- sCD46 inhibited measles virus binding to CD46-expressing cells.
- Binding of sCD46 to cell-surface H increased upon coexpression of measles virus fusion protein.
- sH bound to cell-surface CD46 and inhibited viral binding and infection.
Conclusions:
- The direct interaction between the ectodomains of measles virus H and CD46 is a primary event in measles virus infection.
- Soluble forms of H and CD46 can block measles virus entry, suggesting potential therapeutic applications.