SPring-8, the large synchrotron radiation facility

Release Date

10 Jan, 2011

Kyushu University

<Background>
Measles remains a serious viral infection; it continues to infect tens of millions of people each year worldwide and kills over one hundred thousand of these infected people. Measles also has a serious complication called subacute sclerosing panencephalitis (SSPE), although its frequency is low (approximately one in thirty thousand infected people). Japan has an exceptionally large number of measles patients among developed countries, and the government aims to eliminate measles by 2012 by promoting measles vaccination. Recently, the measles virus has been attracting attention as not only a pathogen but also for its potential applicability for the treatment of cancer; there has been an attempt to modify the virus to be specifically infectious to cancer cells. In 2000, Professor Yanagi’s research group clarified that the measles virus infects cells by binding to the SLAM receptor distributed on the surface of immune cells. In 2007, the group determined the structure of the measles virus H protein, bound to the receptors.

<Research contents>
The measles virus H protein plays an important role in the invasion of the measles virus into cells by binding to its receptor, and also serves as the principal target of the antibodies produced as an immune response of host cells. In this study, Professor Yanagi’s research group purified a large amount of the H protein bound to the SLAM receptor and crystallized this complex, successfully determining its three-dimensional structure using X-rays from SPring-8 beamlines, such as the Structural Biology I Beamline (BL41XU) and Macromolecular Assemblies Beamline (BL44XU).

The H protein showed a structure similar to a propeller with six blades and was bound to SLAM at certain sites on the propeller. It was also found that the SLAM binding sites on the H protein, i.e., the peripheries of the sites important for the virus to infect host cells, were the target of antibodies. Because of this, the measles virus cannot mutate to escape the antibodies (if such a mutation of the virus occurs, the virus becomes unable to infect cells and cannot survive). Therefore, measles virus vaccines are considered to be very effective, unlike those against influenza viruses and human immunodeficiency viruses (HIVs).

In this research, it was also clarified that the H protein has two types of tetramer (a molecule consisting of four subunits) structure. The measles virus is a paramyxovirus; it has long remained unclear how paramyxoviruses fuse to the cell membrane and invade cells. The research results of Professor Yanagi and his colleagues strongly suggest that membrane fusion is triggered by changes in the tetramer structure of the H protein caused following the binding of the virus to its receptor.

<Benefits and future prospects>
Although effective measles virus vaccines have been available, anti-measles virus drugs have not yet been developed. Moreover, there is no effective therapy for SSPE, a very serious complication of measles. The clarification of the structure of the complex of the H protein and the SLAM receptor will enable the design of antiviral drugs that target the sites of binding of the H protein to its receptor. In addition, the clarification of mechanisms of membrane fusion of paramyxoviruses including the measles virus will provide important information that will lead to not only the clarification of cell invasion by viruses but also the development of drugs against paramyxoviruses. Professor Yanagi’s group will continue to study the mechanisms of membrane fusion and cell invasion by the measles virus in more detail.

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