Genes may explain who gets sick from flu

Infection can activate two dramatically different responses

The difference between staying well and suffering days of misery depends on which of two contradictory ways the immune system reacts to infection by the flu. One strong reaction releases inflammatory chemicals leading to sickness, researchers report online August 25 in PLoS Genetics. An equally strong but opposite reaction produces anti-inflammatory compounds and fights off the flu without producing symptoms. 

Most of what researchers know about influenza’s effect on people comes from studies of people who are already sick. But Alfred Hero and his colleagues wanted to know how some people seem to be able to avoid getting sick. The researchers infected 17 volunteers with a strain of seasonal flu called H3N2/Wisconsin.

Nine of the volunteers got sick. Some of the others reported feeling under the weather, but had no clinically discernible symptoms. The researchers drew blood before the flu inoculation and every eight hours for five days after the initial infection. The team then examined the activity of about 22,000 genes in each blood sample.

“The persistent patterns that came out of this were striking to say the least,” says Hero, a computer scientist and electrical engineer at the University of Michigan Medical School.

Gene activity patterns could predict up to 36 hours before symptoms peaked how sick people would get, the researchers found. Those who got sick activated immune chemicals that trigger inflammation and stress responses. “In asymptomatic people the immune response is just as active, but dramatically different in nature,” Hero says. People who stayed well not only repressed the stress response, but also activated anti-inflammation and antioxidant genes.

“This is really exciting data,” says Octavio Ramilo, the head of pediatric infectious diseases at Nationwide Children’s Hospital in Columbus, Ohio. The study illustrates that gene activity analysis may help doctors determine which patients are most in danger of getting seriously ill. But the current study hasn’t put the entire story together yet, he says. Researchers still need to determine whether the different patterns of responses depend upon the person’s genetic makeup, properties of the virus or other factors. Hero adds that the people in the study may react differently to other flu strains or even to the same one under different circumstances.

The technology may one day help doctors diagnose which viruses are infecting babies with fevers and predict which infants will end up in the intensive care unit and which ones can go home.

Such tests may also be important public health tools for preventing flu pandemics, Ramilo says. People who stayed well tended to spread fewer flu viruses than people who got sick, the study showed. So health care workers might be able to test people exposed to a virus and determine from gene activity patterns who needs to be quarantined to limit the spread of infectious diseases. 

Tina Hesman Saey

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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