First flu strain beaten by child determines life-time protection and vulnerability – study

© Ivan Alvarado
The first strain of influenza a person contacts gives a sort of ‘immunological imprinting’ making them resistant to a whole family of similar strains and exposed to mismatched types of flu, a new study revealed.

The research published in the Science journal this week was based on 1,400 people who had been infected at any point in life with two stains of influenza A virus, H5N1 and H7N9.

Both are usually found in birds and only occasionally transmit to humans, but both are highly pathogenic and have high human mortality rates. Epidemiologists study animal strains of flu because the virus constantly mutates and a strain may unexpectedly become easily transmittable between humans and cause a pandemic.

The cases studied by scientists from the University of Arizona in Tucson and the University of California, Los Angeles were mostly from Asia and the Middle East, Science Daily reported. The researchers found that the two strains affected people either severely or mildly depending on which strain of human influenza they contacted first in childhood.

The explanation is that when an individual is fighting off flu, the immune system learns to produce antibodies specific to a protein called hemagglutinin. Such proteins shaped as mushrooms or lollipops cover the surface of a virus and help it attach to a cell and infect it with the viral genome.

There are 18 known influenza A hemagglutinin subtypes, numbered 1 through 18, constituting the first part of a strain’s name. But all of those subtypes, found in both human and animal strains, fall into two large groups, which are different for H5N1 and H7N9 strains.

“In this analogy, let's say you were first exposed to a human 'orange lollipop' flu as a kid,” said UA’s Michael Worobey, one of the two senior researchers behind the paper. “If later in life you encounter another subtype of flu virus, one from a bird and one that your immune system has never seen before but whose proteins also are of a similar 'orange' flavor, your chances of dying are quite low because of cross-protection. But if you were first infected with a virus from the 'blue lollipop' group as kid, that won't protect you against this novel, 'orange' strain.”

The strains of human flu that have circulated for over a century have hemagglutinin subtypes 1, 2, and 3. The first two were predominant before the late 1960s while the third one emerged later. The researchers found that people born before that time were rarely affected severely by the H5N1 bird flu strain, which shares its “flavor” with the older strains of human influenza, but suffered more severely from H7N9 strain. The reverse was true for younger people, who had an H3N2 seasonal flu as their fist strain.

Worobey believes that the same mechanism explains why the historic Spanish flu epidemic of 1918 mostly affected young people, while older people were relatively unaffected. The youths may have been imprinted by an H3- strain unknown to us and were mismatched for the new H1N1 strain.

“The fact that we are seeing exactly the same pattern with current H5N1 and H7N9 cases suggests that the same fundamental processes may govern both the historic 1918 pandemic and today's contenders for the next big flu pandemic,” he said.