Novel mouse model might help uncover mechanism behind Zika infection

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Researchers from John Hopkins University (MD, USA) have utilized a novel mouse model to further investigate the effect of Zika virus on pregnancies, discovering a higher risk of miscarriages in addition to thin brain tissue and inflammation in infants born during infection.

The team also reported that Zika infection appeared to create disorganization in the normally discrete layers of the placenta, and suggest this could be part of the mechanism that allows the virus to cross the placental barrier.

In the study, published recently in Nature Communications, the researchers studied a new mouse model, which unlike previous models, has a completely intact immune system better imitating that in humans.

Utilizing this model, the researchers injected different strains of Zika virus into the reproductive tracts of pregnant mice at several time points. They demonstrated that there was a decreased number of viable pregnancies when Zika was introduced; the number of viable pregnancies remaining ranged from 56–71%, compared with the control where nearly 94% of pregnancies remained viable.

In addition, the group observed that the placenta appeared disorganized in infected mice, which could contribute to the mechanism by which Zika can across the placental barrier. Author and co-leader Irina Burd, from John Hopkins University, commented: “This could be why the fetuses in the Zika-infected mice were so vulnerable to either miscarriage or brain damage.”

However, the team discovered that infection later in the pregnancy had a reduced risk of miscarriage when compared with earlier infections. Moreover, it was observed that pups born after early Zika infection possessed thinner cortexes and larger numbers of inflammatory cells in the brain compared with pups born from mothers infected later. This could indicate that there is less vulnerability to Zika virus later in pregnancy.

Co-leader of the study, Sabra Klein (Johns Hopkins University) stated: “We need to find a way to stop transmission of Zika through the placenta into the fetus, because that is where the damage is being done. In the placentas of our mice, we’re seeing a defense against Zika being mounted, but falling short, especially in early pregnancy, a time that corresponds to the first trimester in humans.”

The researchers hope to conduct further research looking at the long-term effects of infection, which has as-yet been unexplored. For example, by studying the siblings of infants born during Zika infection, Klein explained: “We don’t know if the effects persist in future pregnancies. We’re just dealing with the here and now. We have no idea what the long-term consequences are for the mother.”

Elucidating the mechanisms behind Zika infection through studies such as this could lead to treatments or vaccines against the virus; Burd concluded “If we can determine what is happening, we may be able to find ways to minimize or even eliminate what can be devastating consequences for children of infected mothers.”

Source: Vermillion MS, Lei J, Shabi Y et al. Intrauterine Zika virus infection of pregnancy immunocompetent mice models transplacental transmission and adverse perinatal outcomes, Nat. Comms. doi:10.1038/ncomms14575 (2017) (Epub ahead of print) https://www.eurekalert.org/emb_releases/2017-02/jhub-zmc021617.php

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