Zika virus infection of first-trimester human placentas: utility of an explant model of replication to evaluate correlates of immune protection ex vivo

Petitt, Matthew; Tabata, Takako; Puerta-Guardo, Henry; Harris, Eva; Pereira, Lenore

doi:10.1016/j.coviro.2017.11.008

Cited by 23 publications

(20 citation statements)

References 90 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ZIKV is an arbovirus, with the unique ability to be transmitted vertically across the placenta. Furthermore, trimester-specific effects have been noted in humans and NHP models of ZIKV infection during pregnancy, and the timing of infection during pregnancy may influence the severity of fetal effects [2,[58][59][60][61]. We have previously shown that early gestation ZIKV infection of sheep results in fetal effects, even in the absence of detectable virus at the tissue level [25].…”

Section: Discussionmentioning

confidence: 99%

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

Schwarz

Oliveira

Bonfante

et al. 2020

Viruses

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 99%

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

Schwarz

Oliveira

Bonfante

et al. 2020

Viruses

View full text Add to dashboard Cite

show abstract

“…30 After correcting for multiple testing, none of our analyses revealed a strong signal of a mechanism of immune control. We also saw that the dynamics of the changes in IFN concentration and levels of NK cells and CD8 effector effects observed after ZIKV infection, and shown in Figure 6, were not readily described by any of the generally used models of immune response discussed above (Equations 11,16,17) and illustrated in Figure 5C. In particular, the IFNα response showed an early peak in most, but not all, animals, but this waned in many animals before the plasma viremia was controlled, and continued to increase in some animals after plasma viral load became undetectable.…”

Section: Adaptive Immune Response Modelsmentioning

confidence: 99%

“…Not only is ZIKV detected in blood, it widely disseminates, with viral particles being detected in easily sampled compartments, such as urine, semen, and breast milk . Understanding the rapid viral kinetics and widespread dissemination of ZIKV, including its apparent ability to cross both the blood‐brain barrier and the placental barrier will be vital in assessing and reducing infection risks, and to evaluate the effectiveness of therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling of within‐host Zika virus dynamics

Best

Perelson

2018

Immunological Reviews

View full text Add to dashboard Cite

Recent Zika virus outbreaks have been associated with severe outcomes, especially during pregnancy. A great deal of effort has been put toward understanding this virus, particularly the immune mechanisms responsible for rapid viral control in the majority of infections. Identifying and understanding the key mechanisms of immune control will provide the foundation for the development of effective vaccines and antiviral therapy. Here, we outline a mathematical modeling approach for analyzing the within-host dynamics of Zika virus, and we describe how these models can be used to understand key aspects of the viral life cycle and to predict antiviral efficacy.

show abstract

“…Quantitation of the virus suggests that both amniotic and villous cytotrophoblast cell populations are more susceptible to infection earlier in gestation . Hofbauer cells are a target of Zika virus once inside the villous stroma . Virions are detected in the amniotic fluid, yet it is unclear which population described above is the main reservoir of the virus.…”

Section: Part II the Histopathology Of Placental Infectionmentioning

confidence: 99%

Defense and infection of the human placenta

Heerema-McKenney

2018

APMIS

View full text Add to dashboard Cite

The placenta functions as a shield against infection of the fetus. The innate and adaptive immune defenses of the developing fetus are poorly equipped to fight infections. Infection by bacteria, viruses, and protozoa may cause infertility, spontaneous abortion, stillbirth, growth retardation, anomalies of development, premature delivery, neonatal morbidity, and mortality. However, appreciation of the human microbiome and host cell-microbe interactions must be taken into consideration as we try to determine what interactions are pathologic. Infection is typically recognized histologically by the presence of inflammation. Yet, several factors make comparison of the placenta to other human organs difficult. The placenta comprises tissues from two persons, complicating the role of the immune system. The placenta is a temporary organ. It must be eventually expelled; the processes leading to partuition involve maternal inflammation. What is normal or pathologic may be a function of timing or extent of the process. We now must consider whether bacteria, and even some viruses, are useful commensals or pathogens. Still, recognizing infection of the placenta is one of the most important contributions placental pathologic examination can give to care of the mother and neonate. This review provides a brief overview of placental defense against infection, consideration of the placental microbiome, routes of infection, and the histopathology of amniotic fluid infection and TORCH infections.

show abstract

Zika virus infection of first-trimester human placentas: utility of an explant model of replication to evaluate correlates of immune protection ex vivo

Cited by 23 publications

References 90 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

Mathematical modeling of within‐host Zika virus dynamics

Defense and infection of the human placenta

Contact Info

Product

Resources

About