A guide to inhibit measles infection

Infecting almost 20 million people worldwide each year, the measles virus remains a dangerous, highly contagious disease despite extensive vaccination efforts. However, recent advancements in understanding the pathogen’s binding mechanism could provide a new strategy to fight infection.

Using X-ray crystallography, researchers from the Howard Hughes Medical Institute (HHMI) at Stanford University have determined the structure of the propeller-like attaching molecule, known as measles virus hemagglutinin (MVH). .

The study, published in the online journal Nature Structural and Molecular Biology, showed how the crystallography process directed X-rays through crystals of the protein, allowing the protein’s structure to be deduced from the X-ray diffraction pattern.

The resulting structure revealed that MVH is shaped like a propeller, with its blades spread such that they can attach to the host cell in the infection process. This propeller shape is commonly found on the surfaces of viruses as a protein called a neuraminidase. Viruses such as influenza use a cleft at the centre of the propeller to bind carbohydrates on the cells they infect.

“Neuraminidases act as a kind of general molecular velcro, sticking the virus to the surface of cells,” said HHMI researcher Christopher Garcia.

What makes the measles virus unique is that it doesn’t use carbohydrates to bind to host cells.

“While MVH exhibits the neuraminidase fold, it is a ‘dead’ neuraminidase, having lost all function,” said Garcia.

“Rather, the measles virus hemagglutinin has evolved the ability to bind to two non-overlapping host cell receptors, called SLAM and CD46. This is a completely novel mechanism for this class of viruses. So, if a drug is to block measles virus binding, it has to interfere with both of these receptors.”

The next step, he said, is to solve the structure of MVH attached to the host cell receptors, to elucidate the details of the host-virus attachment. Garcia’s group has begun to analyse the structure of MVH attached to the SLAM receptor.

“Once we have high-resolution pictures of the determinants of this attachment interface, it will be possible to begin to think about therapeutic intervention in that attachment,” he said.