It’s Not You, It’s Flu

The host immune system has a limited impact on the evolution of the influenza virus, A*STAR researchers find.

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The aching muscles, nasal congestion and sore throat associated with flu can be prevented by vaccination, but you must get a new shot every year. The reason for this is the evolution of the influenza virus via a process known as antigenic drift, resulting in the alteration of a key protein called hemagglutinin on the virus’ surface. Antigenic drift allows viruses to evade detection by the host’s immune system.

Scientists are still figuring out the precise mechanisms by which antigenic drift occurs, and previous studies have suggested that the host immune system is the primary determinant in driving influenza virus evolution. “If this is true, mutation patterns in young, immunologically naive children and older adults who have had influenza infections before should be prominently distinct,” said Alvin Han, a graduate student in Sebastian Maurer-Stroh’s lab at the Bioinformatics Institute (BII), A*STAR.

To test this hypothesis, the team, in collaboration with Colin Russell from the Academic Medical Centre at the University of Amsterdam, analyzed 26,725 high quality publicly available hemagglutinin sequences across all four subtypes of seasonal influenza viruses circulating in humans from January 2009 to July 2016. They built a ‘family tree’ of influenza viruses and compared pairs of hemagglutinin sequences, taking into consideration the age of the hosts in which the viruses were identified. This allowed them to obtain the distribution of hemagglutinin mutations observed in young children and older adults.

“We found that viruses infecting children are just as likely to develop mutations as those infecting adults,” Han explained. “Even adjusting for any potential confounding factors such as waning immunity due to old age, we still could not find any imprint of individual host selection pressure on influenza virus evolution. This study thus indicates that individual immune selection has a limited role in the antigenic evolution of influenza viruses.”

The researchers noted that influenza is usually an acute infection in humans. Hence, the duration of infection may not be long enough for the immune system to mount a substantial strain-specific response that drives the viruses towards generating immune-evasive mutants that become fixed in the virus population.

“If individual immune selection is not the primary driving force behind antigenic drift of influenza, antigenic change should then be linked more closely to selection during transmission, with population immunity playing a key role. Therefore, public health measures and interventions targeting transmission are crucial to not only limit viral spread, but also virus evolution,” said Han.

The A*STAR-affiliated researchers contributing to this research are from the Bioinformatics Institute (BII).