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Case Reports
. 2016 May;111(5):287-93.
doi: 10.1590/0074-02760160085. Epub 2016 Apr 29.

Zika virus damages the human placental barrier and presents marked fetal neurotropism

Lucia de Noronha  1 , Camila Zanluca  2 , Marina Luize Viola Azevedo  1 , Kleber Giovanni Luz  3 , Claudia Nunes Duarte Dos Santos  2
Affiliations
Case Reports

Zika virus damages the human placental barrier and presents marked fetal neurotropism

Lucia de Noronha et al. Mem Inst Oswaldo Cruz. 2016 May.

Abstract

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.

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Figures

Fig. 1
Fig. 1. : pathological findings and immunohistochemistry reactions in placental tissues. (A) Histological section of case 1 immunostained by the conventional immunohistochemistry technique, omitting the primary antibody, which was used as a negative control. We observed chronic placentitis (TORCH type) with chronic villous inflammation (histiocytic-predominant villitis - arrow), edema and trophoblastic epithelial lesions (arrow head) as compared to normal villous tissue (dashed arrow). There was an increase in villous Hofbauer cells and villous stromal lymphohistiocytic cells. (B) Histological section of case 1 immunostained with a non-related anti-Chikungunya virus monoclonal antibody as the primary antibody, which was used as a negative control. We observed the same features observed in A (arrow shows histiocytic-predominant villitis, arrow head shows non lesional trophoblastic epithelial cells and dashed arrow shows normal villi). (C-D) Histological section of case 1 immunostained with the anti-flavivirus monoclonal antibody 4G2. Chronic placentitis (TORCH-type) was observed with immunopositivity in Hofbauer cells (arrow) and some histiocytes in the intervillous spaces (dashed arrow). There was no immunopositivity in the trophoblastic epithelium (arrow head).
Fig. 2
Fig. 2. : anatomopathological findings on brain tissues samples stained with H&E. (A) Histological section of brain tissue samples of case 2 with a mildly affected white matter region revealing diffuse microglial hyperplasia, gliosis with reactive astrocytes and microdeposits of calcium (arrow). (B) Histological section of a brain tissue sample from case 3 with a mildly affected white matter region containing microglial nodules (arrow) and neuronophagia (dashed arrow). (C) Histological section of a brain tissue sample from case 4 with a more severely affected white matter region, revealing extensive destruction and infiltration by mononuclear inflammatory cells. Diffuse microglial hyperplasia was also present. In addition, severe gliosis with reactive gemistocytic astrocytes were diffusely distributed. (D) Histological section of a brain tissue sample from case 4 with a more severely affected white matter region showing extensive perivascular cuffing by lymphocytes (arrow). In addition, moderate gliosis with reactive gemistocytic astrocytes (dashed arrow) were diffusely distributed.
Fig. 3
Fig. 3. : pathological findings and immunohistochemical reactions in brain tissues. (A-D) Histological sections of brain tissue samples of cases 2 (A-B) and 3 (C-D) immunostained with 4G2 (B and D) or with a non-related anti-Chikungunya virus monoclonal antibody (A and C). We observed some positive glial cells (arrow) and scattered foci of microcalcifications (dashed arrows). (E-G) Histological sections of brain tissue samples of case 4 immunostained with 4G2 (F-G) or with a non-related anti-Chikungunya virus monoclonal antibody (E) as the primary antibody. We observed some positive gemistocytic glial cells (G - arrow). We also observed scattered positive endothelial cells (F - arrow).
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References

    1. Alpert S, Fergerson J, Noël L. Intrauterine West Nile virus: ocular and systemic findings. Am J Ophthalmol. 2003;136(4):733–735. - PubMed
    1. Baurakiades E, Martins A, Moreschi NV, Souza C, Abujamra K, Saito A, et al. Histomorphometric and immunohistochemical analysis of infectious agents, T-cell subpopulations and inflammatory adhesion molecules in placentas from HIV-seropositive pregnant women. Diagn Pathol. 2011;6: - PMC - PubMed
    1. Benirchke K, Kaufmann P, Baergen RN. Benirchke K, Kaufmann P, Baergen RN.editors . Pathology of the human placenta. New York: Springer Science & Business Media; 2006b. Classifications of villous maldevelopment; pp. 502–507.
    1. Benirchke K, Kaufmann P, Baergen RN. Benirchke K, Kaufmann P, Baergen RN.editors . Pathology of the human placenta. New York: Springer Science & Business Media; 2006a. Infectious diseases; pp. 700–715.
    1. Boussemart T, Babe P, Sibille G, Neyret C, Berchel C. Prenatal transmission of dengue: two new cases. J Perinatol. 2001;21(4):255–257. - PubMed

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