Characterization of Placental Infection by Zika Virus in Humans: A Review of the Literature

Abstract

Objective The aim of the current review is to present a systematic evaluation of reported human placental findings in cases of zika virus (ZIKV) infection. Data sources We reviewed the EMBASE, PUBMED, and SCIELO databases until June 2019, without language restrictions. Selection of studies The search terms placenta AND zika virus were used. The inclusion criteria of the studies were studies that reported placental findings in humans. Experimental studies, reviews, notes or editorials were excluded. A total of 436 studies were retrieved; after duplicate exclusion, 243 articles had their titles screened, and 128 had their abstract read; of those, 32 were included in the final analysis (18 case reports, 10 case series, and 4 cohorts) Data collection We collected data concerning the author, year of publication, study design, number of participants, number of placental samples, onset of symptoms, perinatal outcomes, and main findings on histological analysis. Data synthesis The placental pathologic findings were described as mild and nonspecific, similar to those of other placental infections, including chronic placentitis, chronic villitis, increased Hofbauer cells, irregular fibrin deposits, increased mononuclear cells in the villus stroma, villous immaturity, edema, hypervascularization, stromal fibrosis, calcification, and focal necrosis of syncytiotrophoblasts. Conclusion Zika infection presents unspecific placental findings, similar to other infections in the toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes (TORCH)group. Characterizing and standardizing placental findings after zika virus infection is key to understanding the mechanisms of congenital diseases.

Translational Utility of the Nonhuman Primate Model

“…The need for nonhuman primates in translational research, particularly related to pregnancy, fetal/neonatal development including the CNS, and the role of the immune system, continues to remain a high priority ( 99 , 112 – 116 ). Ongoing studies that explore the role of the maternal-placental-fetal interface are needed to address new approaches to protect against congenital disease and the potential for neurodevelopmental disorders ( 117 – 119 ).…”

Congenital Zika Virus Syndrome: Microcephaly and Orofacial Anomalies

“…Additionally, a narrow palate might be associated with the hypotonia of orofacial musculature commonly observed in children with CZS. Tongue posture abnormalities, the presence of narrow palatine vaults, and alterations such as macroglossia and ankyloglossia are frequently reported by many authors [36,[39][40][41][42]. Microcephaly caused by ZIKV contributes to orofacial disproportions, decreased cranium size, retrognathia, and micrognathia [55].…”

“…Specifically, microcephaly is diagnosed when the head occipitofrontal circumference is below two standard deviations for gestational age and sex, according to the INTERGROWTH-21 standard [36], below the average in relation to sex and gestational age; in the most severe forms, HC can be less than three SDs below the average. Alongside microcephaly, or sometimes even in its absence, brain anomalies may be present, resulting from an interruption of brain development during gestation with consequent skull collapse and disturbance of neuronal and glial migration [32,40]. In a study with seventy-one Brazilian children with prenatal ZIKV infection, the most common abnormalities included calcifications (especially in the cortico-subcortical junction of the white matter), malformations of the cortex, ventriculomegaly, reductions in brain volume, cerebellar hypoplasia, and corpus dysgenesis callosal [41].…”

Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts

“…Maternal Zika virus (ZIKV) infection is associated with adverse pregnancy outcomes including pregnancy loss and fetal malformations 1,2 . Prolonged maternal viremia in humans and nonhuman primates 2-7 suggests there is a pregnancy-specific viral reservoir, and the presence of virus at the maternal fetal interface 8 support the premise that the placenta may serve as a viral reservoir.…”