Zika ‘Replicates and Persists’ in Fetal Brain, Placenta Study strengthens tie to microcephaly Zika virus RNA was found in both fetal brain and placental tissue of Zika-related pregnancy losses and infants born with microcephaly, indicating the virus continues to replicate in a fetus months after a mother’s initial infection, and even after birth, researchers reported.
Examining infant brain tissue, relative levels of Zika RNA were over 1,000-fold higher than those found in second trimester, third trimester, or fullterm placentas. In placental tissue, relative levels of Zika RNA in first trimester placentas were 25- fold higher than in second trimester, third trimester, or full-term placentas, reported Julu Bhatnagar, PhD, of the CDC in Atlanta, and colleagues.
There was a mean 163 days in between the time of maternal symptom onset and detection of Zika virus RNA in brain tissue, and a mean 81 days to detection in placental tissue, they wrote in Emerging Infectious Diseases.
“These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly,” the authors concluded.
“We don’t know how long the virus can persist, but its persistence could have implications for babies born with microcephaly and for apparently healthy infants whose mothers had Zika during their pregnancies,” Bhatnagar said in a statement. “More studies are needed to fully understand how the virus can affect babies.
” The authors stated that Zika virus antigens were previously detected in human and neonatal brains and the placentas of pregnant women, but “the presence of antigens does not necessarily indicate virus replication,” they wrote.
They examined tissue samples from 52 patients with suspected Zika infection, including eight infants who died from microcephaly. They also looked at 44 placental tissue samples — 22 from women with adverse pregnancy outcomes and 22 from women whose pregnancy outcomes were normal.
Overall, 32 of 52 case patients had fetal brain and placental tissue that tested positive for Zika via reverse transcription polymerase chain reaction (RT-PCR) assays. There were also 24 of 32 patients testing positive for Zika, who reported “adverse pregnancy or birth outcomes.” Of these, 23 reported onset of symptoms in the first trimester.
There were 13 infants born with microcephaly — eight who died within a few minutes to 2 months after birth, and five infants born with microcephaly who lived. While brain tissues of these eight infants tested positive for Zika, tests for kidney, liver, spleen, heart, and rib were negative for the virus.
Mothers of these eight infants all reported symptom onset during the first trimester, but 21 of 22 case patients — including eight who tested positive for Zika — who delivered apparently healthy infants reported symptom onset during the second or third trimester. This added to similar research that found the virus is most deadly to the fetus early in pregnancy.
The authors also shed additional light on the mechanism of fetal infection by performing in situ hybridization, which can help identify specific DNA or RNA sequences. In this case, they found Zika virus in tissues of 32 case patients who tested positive for Zika. They also found viral activity in the Hofbauer cells of the placenta, which are involved in preventing the transmission of pathogens from mother to fetus, as well as in neural cells and neurons.
“Our findings indicate that Hofbauer cells may play a role in the dissemination or transfer of Zika virus to the fetal brain, particularly during early pregnancy,” they wrote.
The authors cited their Zika tissue-based PCR testing as a critical method of establishing a retrospective diagnosis of Zika virus.
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