Zika Virus RNA Replication and Persistence in Brain and Placental Tissue

Abstract

Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections.

Persistent Zika virus infection in porcine conceptuses is associated with elevated in utero cortisol levels

“…Such clinical signs and behavioral abnormalities can be partially associated with altered glucocorticoid levels [7]. Zika virus also replicates in the placenta [8][9][10], a crucial player in cortisol traffic from mother to fetus in humans [11] and pigs [12]. Thus, we hypothesize that congenital ZIKV infection may affect in utero cortisol levels.…”

Brief Insights into Zika-Microcephaly Mechanism

“…More recently, data from several epidemiological [5,6] and preclinical [7][8][9] research studies supported this idea, presenting direct evidences for the association between Zika virus infection and fetal disorders, including microcephaly. In a study led in Rio de Janeiro, Brazil, fetal analysis by ultrasonography of 42 infected pregnant women showed that 12 presented fetal abnormalities (29%).…”

Zika virus vaccines

“…For example, more extended periods of viremia have been observed in pregnant women and fetuses 85 , and ZIKV RNA was detected throughout the mother and the fetus in animal models 86–88 . Immune responses of pregnant monkeys and mice infected with ZIKV appear similar compared to non-pregnant infected animals 87,89 .…”