Downregulation of IGF2 expression in third trimester placental tissues from Zika virus infected women in Brazil

ABSTRACTZika 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 remain unknown. In this study, we analyzed placental samples obtained at the time of delivery from a group of twenty-four 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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Zika Virus: Pathology From the Pandemic

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2016-0397-sa ◽

2016 ◽

Vol 141 (1) ◽

pp. 49-59 ◽

Cited By ~ 45

Author(s):

Jana M. Ritter ◽

Roosecelis B. Martines ◽

Sherif R. Zaki

Keyword(s):

Zika Virus ◽

Placental Pathology ◽

Sources Of Information ◽

Third Trimester ◽

Zikv Infection ◽

Gestational Exposure ◽

Pathologic Findings ◽

Control And Prevention ◽

Congenital Zika Syndrome ◽

Insight Into

Context.—As the number of Zika virus (ZIKV) infections continues to grow, so, too, does the spectrum of recognized clinical disease, in both adult and congenital infections. Defining the tissue pathology associated with the various disease manifestations provides insight into pathogenesis and diagnosis, and potentially future prevention and treatment, of ZIKV infections. Objective.—To summarize the syndromes and pathology associated with ZIKV infection, the implications of pathologic findings in the pathogenesis of ZIKV disease, and the use of pathology specimens for diagnosis of ZIKV infection. Data Sources.—The major sources of information for this review were published articles obtained from PubMed and pathologic findings from cases submitted to the Infectious Diseases Pathology Branch at the Centers for Disease Control and Prevention. Conclusions.—Pathologic findings associated with ZIKV infection are characteristic but not specific. In congenital Zika syndrome, tissue pathology is due to direct viral infection of neural structures, whereas in Guillain-Barré syndrome, pathology is likely due to a postviral, aberrant host-directed immune response. Both fetal and placental pathology specimens are useful for ZIKV diagnosis by molecular and immunohistochemical assays; however, the implications of ZIKV detection in placentas from second- and third-trimester normal live births are unclear, as the potential postnatal effects of late gestational exposure remain to be seen.

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