Human Placental Macrophages Susceptible to Zika Virus

Zika virus is transmitted from mother to fetus through placental macrophages, according to a recent study published in Cell Host & Microbe.

Scientists recently reported that a Zika virus infection is most harmful to a fetus during the first trimester of pregnancy. In an effort to better understand the virus, Mehul Suthar, PhD, senior author, assistant professor in pediatrics at the Emory University School of Medicine, and his team set out to learn how a seemingly harmless virus can pass from mother to fetus, causing devastating complications.

Dr. Suthar and his team found that when studying the placental tissue of a fetus that had previously died “as a result of Zika infection,” a viral antigen was detected in Hofbauer cells. These cells originate from a developing fetus’s mesenchymal stem cells. Co-author, Rana Chakraborty, MD, a pediatric infectious disease specialist at Emory stated, “Our study indicates that this cell 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 fetal circulation.”

Using five full-term human placentae samples, which were donated to the study group, the scientists attempted to identify which cell types are most vulnerable to a Zika virus strain that is currently circulating the Caribbean. In addition to Hofbauer cells, the scientists also identified a lower rate of viremia in cytotrophoblast cells, which are the cells in the middle layer of the placental barrier.

The group believe that the Zika virus is transmitted from mother to fetus through infection of the syncytiotrophoblast, the layer that lines the cells from the outside, surrounding and nurturing the fetus. However, in an earlier article published in the same journal, their findings suggested that placental syncytiotrophoblasts can impede viral infections, including Zika infection.

Findings from Dr. Sathur’s recent study demonstrated that less-differentiated cytotrophoblasts permit Zika viral infection. This suggests that once the virus penetrates the syncytiotrophoblast layer of the placenta, it can replicate inside the target cells. However, viral replication was observed at different levels in the sample placentae that the group was working with.

The authors note that the threat of Zika helped reveal that little is known about the placenta, calling it one of the most “understudied human organs.” Dr. Suthar stated, “A concept that is emerging is how host genetics or other non-viral factors, including nutrition and microbiota, influence your immune response… What our study suggests is not everyone is predisposed to having the virus replicate in the placenta, but the full meaning of this needs to be explored further.”

Zika has proven to be a devastating disease, one that can cause lifelong complications to many, either through microcephaly or other effects arising from infection during fetal development stage. There has yet to be active transmission of the virus within the continental United States, however, several US territories have witnessed local infections numbering in the hundreds. Many have called the Zika virus a global health threat, and even officials at the Centers for Disease Control and Prevention (CDC) have urged US lawmakers to take a stance and “act now.”

Previously, the US Senate voted to approve a bill that would grant $1.1 billion in funds to combat active transmission of the Zika virus. This was a small drop from the $1.9 billion that the Obama administration had initially asked for in February. Moreover, Congress has approved $622 million in addition to redirected funds from other programs (such as that of Ebola) to combat Zika; however, the Senate and House have yet to reach a compromise in terms of Zika funding. On May 26, 2016, Tom Friedan, MD, MPH, director of the CDC warned in a National Press Club press conference that the “narrow window of opportunity” to increase Zika prevention measures is quickly closing. He noted that the Zika virus meets the three criteria for legislatures to pass “emergency funding” as it is an unexpected, catastrophic situation which may cause permanent damage.

Dr. Frieden added, “We lost time fighting Ebola because we couldn’t immediately respond rapidly… I fear that we’re losing time with Zika.” He urged lawmakers to pass the bill as mosquito season is set to commence.