In Flu, it’s the Host that Matters the Most

The devastation that any given flu strain can wreak depends on the genetics of the individual, new research suggests.

Every year, hundreds of thousands of people worldwide die from influenza — the very young and very old are particularly vulnerable — but researchers have struggled to understand why certain flu strains prove deadly in certain people.

Now, researchers in Germany, which sees between 10,000 and 30,000 influenza deaths each year, have discovered that an excessive immune response — genetic in origin — accounts for the fatal outcome of the disease in mice. In other words, it might be the host, rather than the virus, that determines how deadly the disease can be.

“Where there are many scientific works dealing solely with the flu virus, we have investigated how the host reacts to an infection,” said Klaus Schughart, head of the Experimental Mouse Genetics research group at the Helmholtz Association of German Research Centres, in a press release announcing his findings. The study has been published in the journal PLoS One.

For their experiments, researchers injected seven different inbred mouse strains with the same amount of type A influenza viruses (pathogens of the type A flu virus account for the vast majority of human deaths from the disease). To their surprise, the researchers were able to spot strong differences in the progression of the influenza among the seven strains. The illness was relatively benign in five of the strains: Although the rodents shed weight, they recovered completely after seven to eight days. However, in two of the mouse strains, the animals’ weight plunged dramatically, leading to death in just a few days.

“The mice die from their own immune defenses, which are actually supposed to protect them against the virus. The immune system produces too many messengers, which have a strong activating effect on the immune cells. These cells then kill tissue cells in the lungs that are infected with the virus,” explained Schughart.

Those overactive cells also destroy healthy lung tissue. Autopsies revealed the dead mice were riddled with a hundred times more viruses than the animals that survived the disease. “It appears that the animals have specific receptors on their cells that make them more receptive to a severe viral infection,” Schughart noted. “It is only now that we are beginning to understand the role played by the genetic factors of the host and what increased receptiveness means in the case of influenza.”

Flu infections in people could progress through a similar course, the researchers speculate, wherein genetic factors could result in a more severe bout of the illness.

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