Femur-sparing pattern of fetal growth after maternal Zika virus infection

Yasri, Sora; Wiwanitkit, Viroj

doi:10.1016/j.ajog.2018.07.009

Cited by 2 publications

(2 citation statements)

References 4 publications

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“…In addition, infected fetuses had visible changes in cranial shape and half of these fetuses (I2F1, I2F2, I3F1, I4F1) were positive for ZIKV by culture or RT-PCR with one (I3F2) having mineralization within the leptomeninges. These morphological changes are consistent with those seen in natural human fetal infection as well as experimental ZIKV NHP infections [11,[63][64][65]. Mineralization within the brain is a well-described characteristic of CZS in humans [3,4,[66][67][68][69][70][71][72], and the mineralization in the leptomeninges of one of the infected fetuses with small cranial circumference strongly suggest that the histopathological changes are due to infection status.…”

Section: Discussionsupporting

confidence: 83%

Experimental Infection of Mid-Gestation Pregnant Female and Intact Male Sheep with Zika Virus

Schwarz

Oliveira

Bonfante

et al. 2020

Viruses

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Zika virus (ZIKV) is an arbovirus that causes birth defects, persistent male infection, and sexual transmission in humans. The purpose of this study was to continue the development of an ovine ZIKV infection model; thus, two experiments were undertaken. In the first experiment, we built on previous pregnant sheep experiments by developing a mid-gestation model of ZIKV infection. Four pregnant sheep were challenged with ZIKV at 57-64 days gestation; two animals served as controls. After 13-15 days (corresponding with 70-79 days of gestation), one control and two infected animals were euthanized; the remaining animals were euthanized at 20-22 days post-infection (corresponding with 77-86 days of gestation). In the second experiment, six sexually mature, intact, male sheep were challenged with ZIKV and two animals served as controls. Infected animals were serially euthanized on days 2-6 and day 9 post-infection with the goal of isolating ZIKV from the male reproductive tract. In the mid-gestation study, virus was detected in maternal placenta and spleen, and in fetal organs, including the brains, spleens/liver, and umbilicus of infected fetuses. Fetuses from infected animals had visibly misshapen heads and morphometrics revealed significantly smaller head sizes in infected fetuses when compared to controls. Placental pathology was evident in infected dams. In the male experiment, ZIKV was detected in the spleen, liver, testes/epididymides, and accessory sex glands of infected animals. Results from both experiments indicate that mid-gestation ewes can be infected with ZIKV with subsequent disruption of fetal development and that intact male sheep are susceptible to ZIKV infection and viral dissemination and replication occurs in highly vascular tissues (including those of the male reproductive tract).Viruses 2020, 12, 291 2 of 23 and negative gestational outcomes when infection occurs during pregnancy. In humans, ZIKV is believed to result in trimester-specific effects to the fetus [2][3][4][5][6][7]. Established animal models of ZIKV infection during pregnancy that result in vertical transmission include non-human primates (NHP) and type-1 interferon/interferon receptor deficient mice. In NHP models, first trimester infection most frequently results in fetal demise and reduced fetal development even in asymptomatic mothers, while second trimester infections tend to produce fetuses with higher viral loads but greater fetal viability [8][9][10]. In all NHP models, fetal pathology ranges from mild to severe manifestations, consistent with Congenital Zika Syndrome (CZS) seen in humans [11][12][13][14][15][16]. While NHP models of ZIKV infection during pregnancy recapitulate human infection, other outbred host models can serve as surrogates when ethical and economic constraints create obstacles to the use of NHP.Sheep offer a unique animal model for translational biomedical research, and have long been used as a model for human pregnancy and fetal development due to longer gestation and comparably staged rates of fetal d...

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Section: Discussionsupporting

confidence: 83%

Experimental Infection of Mid-Gestation Pregnant Female and Intact Male Sheep with Zika Virus

Schwarz

Oliveira

Bonfante

et al. 2020

Viruses

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“…Maternal and fetal telemetric or electrocardiographic leads and catheters (arterial, venous, umbilical, and amniotic) can be surgically placed to continuously monitor metabolic activity, nutrient and gas exchange, and cytokine presence, and to frequently obtain physiologic measurements and biological samples at the maternal–fetal interface [20,21,22,23]. The ability to closely monitor the maternal–fetal interface has led to the extensive use of sheep as model for human pregnancy and fetal development over the last half a century, and has contributed to an understanding of fetal stress and intrauterine growth restriction—both of which are components of maternal ZIKV infection and CZS [17,24,25,26,27,28]. The development of a model with the possibility of real-time monitoring of fetal and maternal physiology has a great potential to contribute mechanistically to the understanding of ZIKV immunopathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Experimental Infection of Pregnant Female Sheep with Zika Virus During Early Gestation

Schwarz

Pozor

et al. 2019

Viruses

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Zika virus (ZIKV) is a vertically and sexually transmissible virus resulting in severe congenital malformation. The goal of this study was to develop an ovine model of ZIKV infection. Between 28–35 days gestation (DG), four pregnant animals were infected with two doses of 6 × 106 PFU of ZIKV; four control animals received PBS. Animals were evaluated for 45 days (D) post-infection (PI) and necropsies were performed. Viral RNA was detected in infected ewe peripheral blood mononuclear cells (PBMC) during the first week PI; however, all fluids and tissues were negative upon culture. Anti-ZIKV IgM (1:400) and neutralizing antibodies were detected in all infected animals. Clinical disease, virus, or ZIKV antibodies were not detected in control ewes. After two weeks PI, fetal loss occurred in two infected animals, and at necropsy, three infected animals had placental petechiation and ecchymosis and one had hydramnion. Fetal morphometrics revealed smaller cranial circumference to crown-rump length ratios (p < 0.001) and relative brain weights (p = 0.038) in fetuses of infected animals compared with control fetuses. Immunophenotyping indicated an increase in B cells (p = 0.012) in infected sheep. Additionally, in vitro experiments using both adult and fetal cell lines demonstrated that ovine cells are highly permissive to ZIKV infection. In conclusion, ZIKV infection of pregnant sheep results in a change in fetal growth and gestational outcomes.

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Femur-sparing pattern of fetal growth after maternal Zika virus infection

Cited by 2 publications

References 4 publications

Experimental Infection of Mid-Gestation Pregnant Female and Intact Male Sheep with Zika Virus

Experimental Infection of Mid-Gestation Pregnant Female and Intact Male Sheep with Zika Virus

Experimental Infection of Pregnant Female Sheep with Zika Virus During Early Gestation

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