Open wide. The hemagglutinin protein on the surface of an influenza virus
allows it to enter into a cell.
Nature Structural & Molecular Biology , advance online publication (22
February 09)
If you had the flu this year you can expect only a brief respite. There are chances that you will again next year and the year after and the year after. Thank you to its rapid evolution, the influenza virus continually slips away from the immune system and continues to lead the efforts of researchers to counteract this. But this week, the researchers report that they caught antibodies that disable multiple varieties of the virus. The findings could help scientists develop a vaccine against pandemic influenza or treatments that Quash many strains of influenza, including the dreaded bird flu.
The key to this advance is in a viral protein known as hemagglutinin name. Viral protein covers the surface and secures to a receptor on the surface of the target cell. Hemagglutinin then performs a molecular gymnastics. These contortions allow the virus membrane to fuse with the cell membrane, opening the way for viral entry.
Vaccines primarily induce antibodies that target hemagglutinin head. But this part of the protein changes rapidly, undermining the immune system. Immunochemist Wayne Marasco of Harvard Medical School in Boston and colleagues found an immutable part of hemagglutinin that could provide a better target when they were looking for antibodies that neutralize the avian flu. Researchers trawl their gigantic library of more than 27 billion human antibodies to determine which lock molecules of H5 hemagglutinin version carried by the avian flu. They identified 10 antibodies which recognize different versions of H5. In solution, the antibodies would block not only H5 but also eight other types of influenza viruses, including the one responsible for the deadly 1918-1919 pandemic flu.
Next, the team tested three antibodies in mice were infected with lethal doses of avian flu. When they received the antibodies before or up to 3 days after infection, most rodents survived, suggesting that the antibodies are therapeutic and preventive.
structural biologist Robert Liddington of the Burnham Institute for Medical Research in San Diego, California, and his team then used x-ray crystallography to break a closeup of an antibody bound to hemagglutinin. Instead glomming on hemagglutinin variable head, the antibody snuggled into three pockets on the tail, or the stem of the virus. When researchers checked with a database of the genomic sequences of 00 variants of the influenza virus, they found that the amino acid sequence of this region remains constant in many viral strains. This means that an antibody that recognizes this region alone could protect against a variety of flu strains, possibly including one that causes bird flu, the researchers conclude.
Marasco The team moves to safety testing in animals and hope to begin clinical trials of the 2010-11 flu season. "I think it is a very good paper," says molecular biologist Brendon Hanson DSO National Laboratories Singapore, because it suggests an "option available" to wedge pandemic.
One version longest of this story appears in the February 27 issue of science.
0 Komentar