One Step Closer to Understanding How Zika Causes Microcephaly

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shutterstock_358625525It is hard to believe that it has been only two months since the CDC declared that Zika virus causes microcephaly.

This link between the virus and the birth defect is the sole reason why we are all still talking about Zika so much, and why new information on how Zika gets from the mother to the baby is in high demand. Although we are still very (very) far away from knowing how Zika crosses the placenta on its way to the fetus, a new study published in Cell Host and Microbe brings us one step closer.

A group from Emory University School of Medicine has discovered that Zika virus can infect, and replicate in, cells in the placenta (the Hofbauer cells.) (1)

Viruses have exactly one purpose when they infect a host cell -- that is to replicate (make multiple copies of themselves.) However, they cannot bind to, and thus infect, any cell; they have to find the right match.

So, knowing what cell type (or types) a virus attaches to is essential in understanding the damage that the virus does in the body. Viruses can only bind to one (sometimes a few) different types of cells. For example, influenza virus attaches to cells in the lung, which is why it causes severe respiratory illness. Similarly, HIV binds to specific immune cells called T cells, which is why people who are HIV positive become immunocompromised in the absence of antiviral drug therapy.

So, if you know which cells are going to be the target of the virus, you can start to think of ways to combat it. For example, if you block a virus's ability to enter into those cells, you stop the replication process. In fact, one class of the HIV drugs available, called an "entry inhibitor," does just that.

Even though it is now clear that Zika virus causes microcephaly (and other brain abnormalities), it is not at all understood how the virus crosses the placenta in order to infect the brain of the developing fetus, but there is a precedent. Certain viruses, including HIV, Herpes simplex virus-2, rubella and cytomegalovirus are known to be able to pass through the placenta and infect the fetus.

Because the placenta acts as a link between the mother's uterus and the fetus, allowing for the exchange of blood and nutrients, when a virus is able to infect a cell in the placenta, this is analogous to riding the HOV lane from the mother's blood into the fetus.

In order to conduct their experiments, the group obtained placentae from mothers who had delivered term babies (>37 weeks) via Cesarean section. Those placentae, which are made up of many different types of cells, can be broken apart so that the cells are separated by type. Zika virus was then added to the different groups of cells, and the ability of the virus to enter the cells was measured.

Another interesting piece of information to come out of this study is that, although there were only five placentae donors, there was variation within the five as to how well the virus performed. This may be a clue to the ongoing question of why some infected mothers have microcephalic babies and others don't.

So, although there is still much work to be done, knowing that Zika virus can infect specific cells of the placenta is a big step in learning how Zika causes microcephaly and creating a drug to stop that process.

In the absence of birth defects, Zika infection (the major symptoms are a fever, rash, joint pain, and conjunctivitis) would be about as newsworthy as the stomach bug. Let's hope that a drug that could stop Zika from causing microcephaly is not far off. Then we can get it out of the headlines.

NOTE:

(1) The role of these cells remains mysterious, but, they are thought to be a type of macrophage found in the placenta - an immune cell that has a role in preventing infection.  Interestingly, there are more of them earlier in pregnancy.