In a new study, researchers found that how successfully a person can fend off the flu depends not only on the virus’ notorious ability to change with the season but also on the strain first encountered during childhood.
The findings offer an explanation for why some patients fare much worse than others when infected with the same strain of the flu virus.
The results also could help inform strategies aimed at curbing the impact of the seasonal flu.
The research was conducted by a team at the University of Arizona.
For decades, scientists and healthcare professionals were vexed by the fact that the same strain of the flu virus affects people to various degrees of severity.
Then, in 2016, the team presented a paper in the journal Science showing that past exposure to the flu virus determines an individual’s response to subsequent infections, a phenomenon called immunological imprinting.
The discovery helped overturn the prior commonly held belief that previous exposure to a flu virus conferred little or no immunological protection against strains that can jump from animals into humans, such as those causing the so-called swine flu or bird flu.
These strains, which have already caused hundreds of spillover cases of severe illness or death in humans, are of global concern because they could gain mutations that allow them not only to readily jump from animal populations to humans but also spread rapidly from person to person.
In the current study, the researchers set out to investigate whether immunological imprinting could explain people’s response to flu strains already circulating in the human population and to what extent it could account for observed discrepancies in how severely the seasonal flu affects different age groups.
The team analyzed health records that the Arizona Department of Health Services routinely obtains from hospitals and private physicians to track flu cases to study how different strains of the flu virus affect people of different ages.
Two subtypes of influenza virus, H3N2, and H1N1, have been responsible for seasonal outbreaks of the flu over the last several decades.
H3N2 causes the majority of severe, clinically attended cases in high-risk elderly cohorts and the majority of overall deaths. H1N1 causes fewer deaths overall and skews more toward young and middle-aged adults.
The health record data revealed a pattern: People first exposed to H1N1 during childhood were less likely to end up hospitalized if they encountered H1N1 again later in life than people who were first exposed to H3N2.
Conversely, those first exposed to H3N2 enjoyed extra protection against H3N2 later in life.
To understand the discrepancy, the researchers dug into the evolutionary relationships between influenza virus strains.
H1N1 and H3N2, it turned out, belong to two separate branches, or groups, on influenza “family tree.”
While infection with one does result in the immune system being better prepared to fight a future infection from the other, the protection against future infections is much stronger when exposed to strains from the same group it has battled before.
In other words, the ability to fight off the flu virus is determined not only by the subtypes we have encountered over the course of our lives but also by the sequence in which we have encountered them.
The molecular causes of this effect are currently being studied, according to the researchers.
The researchers hope that their findings may help predict which age groups might be severely affected during future flu seasons based on the subtype circulating, which in turn may help health officials prepare an adequate response, such as doling out limited vaccines by cohort.
One author of the study is Michael Worobey, head of the Department of Ecology and Evolutionary Biology.
The study is published in the open-access journal PLoS Pathogens.
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