There was a baffling case. The 2.5-year-old French girl was in good health, but in 2011, she was hospitalized because she had trouble breathing. After testing for a variety of bacterial and viral infections, her doctors diagnosed his illness as severe flu and began to deal with the drug Tamiflu. The girl lived, but she spent 20 days in hospital, some of that time on a ventilator to help him breathe.
Now, researchers have understood why the girl almost died of a disease that many of us get -and-survive each year. They identified a mutated gene that crippled its defenses against the flu virus. The study suggests that defective genes could explain other cases of fatal influenza.
You might think that your last fight flu was bad, but if it did not you land at the hospital, the doctors do not consider "severe." The number of people who come down with severe flu each year depends on the strain of flu virus that is in circulation, but young children and the elderly are usually the most susceptible. "These people would have died before the age of intensive care," the doctor Jean-Laurent Casanova at Rockefeller University in New York City. Although doctors have improved to save people with severe flu, researchers have not understood why most of them have become so bad in the first place.
In previous studies, Casanova and his colleagues discovered a number of mutations that alter the immune system's ability to fight certain infections, such as herpes encephalitis, a type of brain inflammation. To determine if the girl made all the mutations that could explain his illness, the researchers sequenced the part of his DNA that code for proteins. They found that the two copies of IRF7 girl gene were mutated. His mother and father carried different mutations in this gene. However, both parents also had a normal copy of IRF7 , so they were healthy. Because the girl inherited a defective version of the gene from each parent, she had no normal copy.
IRF7 is one of our immune system control switches. When viruses infect our cells, it cranks genes that code for antiviral proteins known as type III interferons name I and type. But the versions of IRF7 realized that the girl did not do their work, the researchers determined mutated. For example, the team tested the dendritic cells of the girl, usually a major source type I interferons and III. In response to the flu virus, activity type III type I interferon genes and abnormally low in the patient's dendritic cells, reports the online team today Science . The researchers also measured the production of type I interferon dendritic cells: α2 interferon. Its dendritic cells fact none of this antiviral protein.
Casanova and his colleagues also wanted to test how mutations of cells that are attacked by the virus affected. Influenza viruses invade the cells lining the lungs, but obtaining these patient cells is difficult. So the researchers translated some of the cells of the daughter of the skin stem cells, then coaxed to specialize in lung cells. Following exposure of these cells and the people of control healthy cells with influenza viruses, researchers were then tested for a viral protein. Compared to control cells, about twice as many lung cells were infected by the virus.
"severe influenza is not just a viral disease, there is also a genetic disease," says Casanova. The researchers identified mutations are extremely rare, so they probably are not many cases severe influenza among children. But researchers are looking for different mutations in IRF7 and other genes related immune system that children also lower defenses. He added that the results suggest the treatment children who have severe flu with interferon-α.
"It is a very elegant study," says immunologist Paul Thomas research Hospital St. Jude children in Memphis, Tennessee. " they show only one mutated gene can control the sensitivity "on severe influenza. Viral immunologist Jacco Boon of the University of Washington in St. Louis agrees." It is an excellent paper for the field "and provides "very convincing evidence" that these mutations have left the girl vulnerable to disease, he said.
The researchers studied patient is now almost 7, and n 't had another episode of severe influenza, with annual shots of the flu. But his good health poses a mystery. IRF7 offers protection against other viruses and the mice lacking the gene quickly succumb to viral infections. However, the girl did not become seriously ill. "The sensitivity to flu and not these other viruses is fascinating," said Boon. Casanova suggests that other genes could intervene to IRF7 to control these infections.
0 Komentar