The human respiratory infection caused by the influenza virus strain H1N1—popularly known as swine flu—was first recognized in the spring of 2009. A few months after the first swine flu cases were reported, rates of confirmed H1N1-related illness increased in much of the world. As a result, the World Health Organization declared the infection a global pandemic. However, the pandemic was declared over in August 2010. Currently, H1N1 is still circulating in humans as a seasonal flu virus, and it is included in the current seasonal flu vaccine (2016-2017). One of the groups at increased risk of infection is pregnant mothers.
During pregnancy, a mother’s immune system is suppressed to protect the fetus, which is perceived as a foreign body because it is genetically different. It is not surprising, then, that pregnant women are at increased risk of developing infection with influenza and, once infected, are more likely to develop severe disease. A 2010 World Health Organization analysis of the 2009 H1N1 influenza pandemic found that pregnant women were 7 times more likely to be hospitalized and twice as likely to die from H1N1 infection than non-pregnant women. Now, results from a new study highlight potential mechanisms at the basis of the increased susceptibility of pregnant women to H1N1 infection. The study (Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice) published on March 8, 2017, shows that, in pregnant mice, the H1N1 influenza virus causes more severe infections and mutates into a more virulent strain in only a few days.
Gülsah Gabriel, co-lead author of the study, said in a press release: “The first line of defense of the immune system, the innate immune response, is not acting quickly enough to clear the virus. The virus takes advantage of this permissive environment and mutates very fast. This is what influenza viruses do best. The new variants are responsible for increased virulence.”
For the study, researchers used a mouse model that mimics human pregnancy. Previous influenza studies in mice evaluated syngenic pregnancies—mice were pregnant with genetically identical fetuses. However, these pregnancies do not mimic natural human pregnancies, which are allogenic—babies are the product of the combined genes of a mother and father. Thus, in allogenic pregnancies, the fetuses differ genetically from the mother. The researchers found that the immune system is more suppressed in allogenic pregnancies than in syngenic pregnancies.
To understand immune suppression in mice with allogenic (genetically distinct pregnancies), the researchers examined gene expression patterns in immune cells during infection. They found that the genes responsible for releasing cytokines such as type 1 interferon were suppressed, resulting in a weak initial response to infection. In addition, genes responsible for activating and recruiting cytotoxic T cells to the site of infection—the lungs—were suppressed, resulting in impaired migration of these cells to the lungs, where they directly attack the virus.
The researchers also found that virus variants that specifically counteract type I interferon response and mediate increased viral pathogenicity appeared quickly following infection in pregnant mice, but not in non-pregnant mice.
The study results underscore the importance of influenza vaccination compliance in pregnant women.