Animal Models of Zika Virus Infection during Pregnancy

Caine, Elizabeth A.; Jagger, Brett W.; Diamond, Michael S.

doi:10.3390/v10110598

Cited by 60 publications

(47 citation statements)

References 94 publications

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“…Several lines of evidence showed the existence of ZIKV antigens in the chronic villi of a human placenta from a mother who gave birth to an infant with microcephaly , and isolation of ZIKV RNA from placental tissue of mice infected with the ZIKV (Caine et al, 2018), suggesting that the ZIKV may penetrate the placental barrier to infect the infant brain. Recent studies reported that the ZIKV is able to infect and replicate in Hofbauer cells that are primary human placental macrophages and in cytotrophoblasts, suggesting a route of intrauterine transmission that the ZIKV crosses the fetal compartment by directly infecting the placental cells (Quicke et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of the Zika Virus Crossing the Placental Barrier and the Blood-Brain Barrier

Chiu¹,

Chu²,

Liao³

et al. 2020

Front. Microbiol.

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Zika virus (ZIKV) infection causes severe neurological symptoms in adults and fetal microcephaly and the virus is detected in the brain of microcephaly and meningoencephalitis patient. However, the mechanism of ZIKV crossing the physiological barrier to the central nervous systems (CNS) remains elusive. The placental barrier and the blood brain barrier (BBB) protect the fetus from pathogens and ensure healthy brain development during pregnancy. In this study, we used human placenta trophoblasts cells (JEG-3) and human brain-derived endothelial cells (hCMEC/D3) as in vitro models of the physiological barriers. Results showed that ZIKV could infect JEG-3 cells effectively and reduce the amounts of ZO-1 and occludin between adjacent cells by the proteasomal degradation pathway, suggesting that the permeability of the barrier differentially changed in response to ZIKV infection, allowing the virus particle to cross the host barrier. In contrast, ZIKV could infect hCMEC/D3 cells without disrupting the BBB barrier permeability and tight junction protein expression. Although no disruption to the BBB was observed during ZIKV infection, ZIKV particles were released on the basal side of the BBB model and infected underlying cells. In addition, we observed that fluorescence-labeled ZIKV particles could cross the in vitro placenta barrier and BBB model by transcytosis and the action of transcytosis could be blocked by either low temperature or pharmacological inhibitors of endocytosis. In summary, the ZIKV uses a cell-type specific paracellular pathway to cross the placenta monolayer barrier by disrupting cellular tight junction. In addition, the ZIKV can also cross both the placenta barrier and the BBB by transcytosis. Our study provided new insights into on the mechanism of the cellular barrier penetration of ZIKV particles.

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Section: Discussionmentioning

confidence: 99%

The Mechanism of the Zika Virus Crossing the Placental Barrier and the Blood-Brain Barrier

Chiu¹,

Chu²,

Liao³

et al. 2020

Front. Microbiol.

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“…Passive immunization reduces or prevents ZIKV infection in nonpregnant rodents and macaques (23,25,26,31,32). In addition, antibodies diminish ZIKV viral burden in the placenta and fetal organs, and also reduce fetal demise in mouse pregnancy models (33)(34)(35). Some of these ZIKV mouse pregnancy models reproduce features of the human disease, including brain pathology (4-6).…”

Section: Discussionmentioning

confidence: 99%

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Rompay¹,

Coffey²,

Kapoor

et al. 2020

Preprint

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Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmissionand fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement in vitro (ADE) and extend their half-lives. Here we report on prophylactic co-administration of the Fc-modified antibodies to pregnant rhesus macaques challenged 3 times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV. Significance statement:Zika virus (ZIKV) infection during pregnancy can cause fetal abnormalities. Vaccines against ZIKV are under development, but because of potential safety concerns due to disease enhancing antibodies, and the time required by active immunization to induce protective antibodies, there is a need to explore alternative strategies. Recombinant monoclonal antibodies can be modified to prevent enhancement of infection, and thus could be an efficacious and safe alternative to vaccines to confer rapid protection. We show that prophylactic administration of two engineered antibodies, Z004 and Z021, to pregnant macaques partially protects against fetal neurologic damage and limits vertical transmission of ZIKV.

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“…Multiple mouse models have been proposed to decipher the mechanisms of ZIKV disease pathogenesis (14, 15). These models allow the investigation of several key features of human infection, such as neuronal damage (16, 17), sexual and vertical transmission (18–21), fetal demise and CZS (22–25). However, while non-structural ZIKV proteins efficiently inhibit innate antiviral responses in humans (26, 27) allowing viral replication, ZIKV replicates poorly in wild-type mice due to its NS5 protein’s inability to antagonize STAT2 and type I interferon (IFN) response as in humans (28).…”

mentioning

confidence: 99%

Genetic diversity of Collaborative Cross mice controls viral replication, clinical severity and brain pathology induced by Zika virus infection, independently of Oas1b

Manet¹,

Simon‐Lorière

Jouvion

et al. 2019

Preprint

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1The explosive spread of Zika virus (ZIKV) has been associated with major variations in severe 2 disease and congenital afflictions among infected populations, suggesting an influence of host 3 genes. We investigated how genome-wide variants could impact susceptibility to ZIKV infection 4 in mice. We first describe that the susceptibility of Ifnar1 knockout mice is largely influenced by 5 their genetic background. We then show that the broad genetic diversity of Collaborative Cross 6 mice, which receptor to type I interferon (IFNAR) was blocked by anti-IFNAR antibody, 7 expressed phenotypes ranging from complete resistance to severe symptoms and death with large 8 variations in the peak and rate of decrease of plasma viral load, in brain viral load, in brain 9 histopathology and in viral replication rate in infected cells. Differences of susceptibility 701 Wakimoto M, Rabello RS,

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Animal Models of Zika Virus Infection during Pregnancy

Cited by 60 publications

References 94 publications

The Mechanism of the Zika Virus Crossing the Placental Barrier and the Blood-Brain Barrier

The Mechanism of the Zika Virus Crossing the Placental Barrier and the Blood-Brain Barrier

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Genetic diversity of Collaborative Cross mice controls viral replication, clinical severity and brain pathology induced by Zika virus infection, independently of Oas1b

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