In the early 2015, several cases of patients presenting symptoms of mild fever, rash,
conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all
patients lived in a dengue endemic area, molecular and serological diagnosis for
dengue resulted negative. Chikungunya virus infection was also discarded.
Subsequently, Zika virus (ZIKV) was detected by reverse transcription-polymerase
chain reaction from the sera of eight patients and the result was confirmed by DNA
sequencing. Phylogenetic analysis suggests that the ZIKV identified belongs to the
Asian clade. This is the first report of ZIKV infection in Brazil.
An unusually high incidence of microcephaly in newborns has recently been observed in
Brazil. There is a temporal association between the increase in cases of microcephaly
and the Zika virus (ZIKV) epidemic. Viral RNA has been detected in amniotic fluid
samples, placental tissues and newborn and fetal brain tissues. However, much remains
to be determined concerning the association between ZIKV infection and fetal
malformations. In this study, we provide evidence of the transplacental transmission
of ZIKV through the detection of viral proteins and viral RNA in placental tissue
samples from expectant mothers infected at different stages of gestation. We observed
chronic placentitis (TORCH type) with viral protein detection by immunohistochemistry
in Hofbauer cells and some histiocytes in the intervillous spaces. We also
demonstrated the neurotropism of the virus via the detection of viral proteins in
glial cells and in some endothelial cells and the observation of scattered foci of
microcalcifications in the brain tissues. Lesions were mainly located in the white
matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain
reaction. We believe that these findings will contribute to the body of knowledge of
the mechanisms of ZIKV transmission, interactions between the virus and host cells
and viral tropism.
Zika virus (ZIKV) infection in humans has been associated with congenital malformations and other neurological disorders, such as Guillain-Barré syndrome. The mechanism(s) of ZIKV intrauterine transmission, the cell types involved, the most vulnerable period of pregnancy for severe outcomes from infection and other physiopathological aspects are not completely elucidated. In this study, we analyzed placental samples obtained at the time of delivery from a group of 24 women diagnosed with ZIKV infection during the first, second or third trimesters of pregnancy. Villous immaturity was the main histological finding in the placental tissues, although placentas without alterations were also frequently observed. Significant enhancement of the number of syncytial sprouts was observed in the placentas of women infected during the third trimester, indicating the development of placental abnormalities after ZIKV infection. Hyperplasia of Hofbauer cells (HCs) was also observed in these third-trimester placental tissues, and remarkably, HCs were the only ZIKV-positive fetal cells found in the placentas studied that persisted until birth, as revealed by immunohistochemical (IHC) analysis. Thirty-three percent of women infected during pregnancy delivered infants with congenital abnormalities, although no pattern correlating the gestational stage at infection, the IHC positivity of HCs in placental tissues and the presence of congenital malformations at birth was observed. Placental tissue analysis enabled us to confirm maternal ZIKV infection in cases where serum from the acute infection phase was not available, which reinforces the importance of this technique in identifying possible causal factors of birth defects. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of some aspects of the pathophysiology of ZIKV.
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