Zika Virus Exploits Pregnant Women's Immune Systems to Infect & Replicate

New research from the Keck School of Medicine at University of Southern California (USC) has found that the Zika virus—known for causing devastating birth defects such as microcephaly in newborns—targets specific white blood cells to suppress pregnant women’s immune systems, which allows it to spread.

The virus works to “handicap” the immune system in a way comparable to HIV, senior study author Jae Jung, distinguished professor and chair of the Department of Molecular Microbiology and Immunology at the Keck School of Medicine, noted in a recent press release.

“Pregnant women are more susceptible to the Zika virus because pregnancy naturally suppresses a woman’s immune system so her body doesn’t reject the fetus—essentially it’s a foreign object,” Dr. Jung explained. “Our study shows pregnant women are more prone to immune suppression. Zika exploits that weakness to infect and replicate.”

Even though it is known that pregnant women have increased susceptibility to infection and the fear of microcephaly and other associated birth defects is what has researchers desperate to develop a vaccine, Dr. Jung pointed out that none of the phase 1 clinical trials for Zika vaccine candidates have included this population thus far.

“The Zika virus vaccines in development seem to be highly effective, but they’re being tested among non-pregnant women with different body chemistry compared to pregnant women,” Dr. Jung commented. “It’s feasible the recommended vaccine dose—thought effective for non-pregnant women—may not be potent enough for pregnant women because their bodies are more tolerant of viruses.”

In an experiment, they infected blood samples that had been collected from non-pregnant women and pregnant women with African and Asian strains of the virus. At peak infection, the researchers found that the virus targeted specific white blood cells known as CD14+ monocytes that go on to turn into macrophages, which are “trash bags that swallow viruses, bacteria, and cellular debris to make the body healthy,” according to the press release. Furthermore, they found that the Asian strain in particular “pushed” these white blood cells to become M2 macrophages that essentially deliver a false message to the immune system that the threat is over, which allows the virus to replicate.

It is worth noting that higher levels of these M2 macrophages are already present in pregnant women in order “to prevent the womb from rejecting the fetus.” The researchers found that the Asian strain creates a surge in M2 macrophage replication, which ultimately results in immune system suppression. Furthermore, they found that pregnant women are most vulnerable to the Asian Zika virus during their first and second trimesters.

“Zika virus infection of merely 4% of the target white blood cells was enough to convert a big population of ‘white knights’ into immune suppressive M2 macrophages. African Zika virus infection increased immune suppression to around 10%. This number skyrocketed to almost 70% for expectant mothers infected by the Asian Zika virus,” according to the press release.

The researchers compared the findings yielded from their experiment with blood samples taken from 30 pregnant women—10 from each trimester—who had been diagnosed with the Asian strain of Zika virus. Furthermore, they assessed blood samples taken from 15 uninfected pregnant women—about five from each trimester.

They found that expression of the genes ADAMTS9 and FN1—known to be associated with pregnancy complications—was “abnormally high” in the samples taken from the 30 pregnant women diagnosed with Asian Zika virus infection. Increased levels of ADAMTS9 may account for underweight newborns and complicated delivery; womb abnormalities, high maternal blood pressure, and “unusually small babies,” have all been associated with high levels of FN1 in past research.

As mosquito-borne illnesses become more prevalent because of environmental issues such as climate change and global warming, it is important that researchers continue to make developments that work to increase understanding regarding who is most susceptible to these infections. The more that is known, the better researchers and health officials can work to protect those who are most vulnerable.