How Zika virus infiltrates the placenta

The very cells charged with protecting a developing foetus appear to be instrumental in Zika virus infecting unborn babies.

Researchers in Atlanta, Georgia analysed placental cells and found immune cells called Hofbauer cells seemed to help ferry Zika across the placental barrier. They published their findings in Cell Host & Microbe.

Earlier this month, Zika virus was found to cause birth defects in mice including microcephaly, where babies are born with a smaller than normal head.

Plenty of viruses are capable of crossing the placenta – a large, flat organ inside the uterus that nourishes the foetus via the umbilical cord. But how Zika manages the feat has been a mystery.

A likely candidate has been placental immune cells called Hofbauer cells. Discovered more than a century ago, they arise from the connective tissue stem cells of a developing foetus and have direct access to foetal blood supply.

Lead authors Kendra Quicke and James Bowen from Emory University and colleagues examined Hofbauer cells from five Zika-infected full-term placentas, along with another type of placental cells, cytotrophoblasts. They play a role in the foetus’ implantation into the uterine wall.

Indeed, they found the Zika virus in Hofbauer cells and, to a lesser extent, cytotrophoblasts.

When they took Hofbauer cells and infected them with a strain of Zika isolated from a patient in Puerto Rico in December 2015, which was similar to the strain currently tearing through Brazil, Quicke, Bowen and their team saw the cells allowed the virus to infect and replicate inside them.

The cells also switched on anti-viral genes and exuded inflammatory molecules, but there was very little cell death, showing Zika was good at keeping their infected host cells alive.

What they think happens is Zika virus, travelling through the pregnant woman’s blood, worms its way into the placenta. There, Hofbauer cells and cytotrophoblasts become infected and the virus replicates inside them.

Once they bust out of Hofbauer cells and cytotrophoblasts, the Zika virus shimmies its way into the foetal blood supply via capillaries entwined in the placenta. It’s then an easy journey to the foetus via the umbilical cord.

Interestingly, the amount of viral replication and inflammatory response in cells varied widely between donors.

For instance, the researchers saw a 35-fold increase in the virus between three and 48 hours after infection in one donor’s placental cells. But in another, the virus multiplied just 2.5 times, and only between 48 and 96 hours post-infection.

Genetic differences and non-genetic factors such as nutrition are likely behind these different responses, the researchers write.

Further studies, they add, should examine when Hofbauer cells and cytotrophoblasts are most susceptible to infection.

The Centres for Disease Control and Prevention recently published data that indicated Zika infection during the first trimester of pregnancy, or early in the second, was associated with higher rates of babies born with microcephaly.