Poliovirus research

[Guest guest]

Of course the researchers first thoughts are about how this can help

make a better vaccine. Better doesn't necessarily mean safer.

http://news.uns.purdue.edu/x/2008b/081208RossmannPolio.html

December 8, 2008

Biologists spy close-up view of poliovirus linked to host cell

receptor

WEST LAFAYETTE, Ind. - Researchers from Purdue and Stony Brook

universities have determined the precise atomic-scale structure of

the poliovirus attached to key receptor molecules in human host cells

and also have taken a vital snapshot of processes leading to

infection.

The virus binds to a receptor on the cell to form a single complex.

" This structure had been predicted, but the predictions were not as

accurate as we had thought, " said Rossmann, Purdue's Hanley

Distinguished Professor of Biological Sciences. " What we have now is

the real structure, as opposed to a prediction of the receptor

molecule. We also have a much higher resolution view of the complex

of the receptor when bound to the virus. "

The work was carried out by Ping Zhang, a Purdue doctoral student,

and others working in Rossmann's laboratory in collaboration with the

group at Stony Brook University in New York.

" These findings show the detailed relationship between atoms in the

receptor and atoms in the virus, " Rossmann said.

The research, which was funded by the National Institutes of Health,

is not immediately geared toward medical applications. However, such

findings might one day help scientists design better vaccines for the

poliovirus and aid in research into the infection processes of other

viruses, Rossmann said.

The findings are detailed in a research paper that appeared on Nov.

25 in the journal Proceedings of the National Academy of Sciences.

The poliovirus has three " serotypes, " which cause different effects

in people. All three serotypes use the same receptor, and Zhang

studied how each serotype binds to the receptor.

The virus is roughly spherical and is made up of 60 triangular facets

forming a geometric shape called an icosahedron. Each of the 60 units

contains a site that can attach to a host cell's receptor molecules.

The receptor molecules are called CD155, for cellular differentiation

protein, and are made up of a single protein bound to the membrane

that envelops a cell. The part outside the cell is divided into three

sections, or domains.

The virus binds to a specific domain, and the new high-resolution

analysis shows the atomic structure at this attachment point.

Zhang used a method called X-ray crystallography to visualize and

study the atomic structure of CD155 and electron microscopy to study

the combined virus and CD155 receptor molecule.

Though cellular receptors are designed to carry out specific chemical

processes for the cell, viruses have developed ways to use them for

gaining entry into cells.

" The virus has learned, to the disadvantage of the cell and human

beings, to attach itself to this particular receptor molecule in

order to enter the cell, " Rossmann said.

The researchers also found what happens next by looking at how the

virus disintegrates in the cell in order to deliver its genetic

material to infect the host.

" These research results provide a detailed analysis of how a virus

can enter its host cell, " Rossmann said.

Polioviruses cause poliomyelitis, a human disease that affects the

central nervous system, injuring or destroying the nerve cells that

control the muscles. Though effective vaccines have been developed

against polioviruses, scientists do not have a clear understanding of

how these viruses attach to receptor molecules on cells to initiate

infection.

The authors listed on the paper are Zhang; Steffen Mueller, a

postdoctoral research associate at Stony Brook; Marc Morais, a former

Purdue postdoctoral research associate; Carol M. Bator, a technical

research assistant at Purdue; Purdue electron microscopist Valorie D.

Bowman; Hafenstein, a postdoctoral research associate at

Purdue; Eckard Wimmer, a distinguished professor of molecular

genetics and microbiology at Stony Brook; and Rossmann.