More light on how Zika virus infects the placenta

Hofbauer cells
A Zika virus strain infects and replicates in Hofbauer cells and cytotrophoblasts, suggesting a route for Zika virus to cross the placental barrier. – Image: Quicke and Bowen et al./Cell Host & Micro

Some pregnant women who are infected with Zika virus transmit the infection to the foetus (vertical transmission). Researchers now know how the virus is able to cross the placental barrier and infect the foetus.

The Zika virus infects and replicates in immune cells of the placenta (Hofbauer cells). The infected cells, which are not killed, allow the virus to pass through the placenta of pregnant women and infect the brain cells of the foetus. The results are published today (May 27, 2016) in the journal Cell Host & Microbe.

That Zika virus infects the Hofbauer cells became clear when an earlier study found Zika viral antigen in these cells that were collected from the placental tissue of a foetus that unfortunately died as a result of Zika virus infection.

Since Hofbauer cells have direct access to foetal blood vessels, transmission of the virus to the foetus becomes easier when these cells are infected with Zika virus.

Mehul S. Suthar, the Corresponding author from the Emory University School of medicine, Atlanta, U.S., and his team found that the virus can also infect another type of placental cell called the cytotrophoblasts, but only after a couple of days unlike in the case of Hofbauer cells. Cytotrophoblasts cells are found in the middle layer of the placental barrier.

The team undertook lab studies using Hofbauer cells and cytotrophoblasts derived from full-term placentae of five women who delivered by Caesarean section. They found that both cells types were permissive to Zika virus infection. The Zika virus used for the study was a strain currently circulating in Puerto Rico.

“Our study indicates that Hofbauer cell type may be a target for Zika virus in the placenta and replication in these cells may allow the virus to cross the placental barrier and enter the foetal circulation,” Rana Chakraborty, a co-author of the paper from Emory said in a release.

The placental cells from the five donors showed different levels of viral replication, inflammation and antiviral gene expression, likely reflecting differences in genetics in these individuals.

Hence, some women may have the capacity to restrict Zika virus at different stages of the viral replication cycle. Such differences in pregnant women may be the reason why some women end up transmitting the virus to the foetus while some others don’t. “Women with more susceptible Hofbauer cells may support higher levels of the virus replication and subsequent spread to the developing foetal nervous system,” they write.

Since infection during the first trimester or early second trimester has been associated with the observed increase in infants born with microcephaly, future studies should be directed at finding out when the Hofbauer and Cytotrophoblasts cells are most susceptible to Zika virus infection (first, second or third trimester).

Since Hofbauer cells have been found to be the target cell within the placenta, antiviral therapies should be developed to prevent virus replication within these cells.


Related stories and links:

How  Zika virus causes microcephaly studied

A ‘turning point’ in the Zika outbreak

 

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