Immune adaptation in pregnancy could lead to more virulent flu strains

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Researchers have evaluated mouse models to uncover why influenza infection can be more severe during pregnancy, demonstrating that immune adaptation during pregnancy may allow the H1N1 influenza virus to mutate into a more virulent strain. This could provide some explanation as to why pregnant women are at such an increased risk of severe infection during influenza pandemics.

It has been well documented that pregnant women are at the highest risk during influenza pandemics; WHO analysis of the 2009 H1N1 pandemic reported that pregnant women were 7-times more likely to be hospitalized and twice as likely to die from influenza infection compared with non-pregnant women.

The study, published recently in Cell host & Microbe, aimed to look at the biological mechanisms behind this increased risk. Previous studies have evaluated mouse models with genetically-identical syngenic fetuses; however, these do not mimic human pregnancies, meaning the results might not be translatable. The team therefore studied both syngenic pregnancies and genetically-different semiallogenic pregnancies in mice.

The team discovered that, compared with syngenic pregnancies, mice with allogenic pregnancies had increased immune suppression. In addition, when mice with allogenic pregnancies were compared with non-pregnant mice, with the group observed a restricted immune response, including a reduced type I interferon response and impaired CD8 T-cell migration into the lungs. “The entire immune system is damped down to protect the fetus,” explained co-lead author Petra Clara Arck from the University Medical Center Hamburg–Eppendorf (Germany).

The researchers hypothesized that this reduced immune response fails to clear the influenza virus in turn allowing the emergence of new viral variants, which may be more severe.

“In this environment of a dampened innate immune system, the virus has a chance to escape and become more virulent,” explained co-lead author Gülsah Gabriel (Heinrich Pette Institute, Germany). “This suggests that during pregnancy, a typical influenza infection could hit very hard.”

More virulent variants of the influenza virus have been reported in pregnant women in previous studies; however, these studies have not been large enough to confirm that the more severe variants are more frequent. In order to confirm this, the group hopes carry out further research looking for viral mutations in pregnant women suffering from influenza.

Confirming these findings in humans would emphasize the importance of complying with influenza vaccinations schemes for pregnant women, in addition, it could open novel avenues for therapeutics.

Source: Engels G, Hierweger AM, Hoffmann J et al. Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice. Cell Host Microbe. 21 (3), 321–333 (2017); www.eurekalert.org/pub_releases/2017-03/cp-did030217.php

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