Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages

Zimmerman, Matthew G.; Quicke, Kendra M.; O’Neal, Justin T.; Arora, Nitin; Machiah, Deepa; Priyamvada, Lalita; Kauffman, Robert C.; Register, Emery; Adekunle, Oluwaseyi; Swieboda, Dominika; Johnson, Erica L.; Cordes, Sarah; Haddad, Lisa; Chakraborty, Rana; Coyne, Carolyn B.; Wrammert, Jens; Suthar, Mehul S.

doi:10.1016/j.chom.2018.10.008

Cited by 112 publications

(122 citation statements)

References 61 publications

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“…Given that transport of maternal IgG across the placenta is minimal during the first trimester and rises dramatically between 22 and 26 weeks of gestation (Simister and Story, 1997;Palmeira et al, 2012), Matthew al. showed that DENV cross-reactive mAbs bound to the ZIKV undergo FcRnmediated transcytosis across the placenta to productively infect human placental macrophages (Zimmerman et al, 2018). In the current study, the ZIKV crossing the placenta barrier cells was directly visualized by using Atto647N-ZIKV particles (Figure 6A).…”

Section: Discussionmentioning

confidence: 56%

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: 56%

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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“…Such antibodies could theoretically mediate antibodydependent enhancement (ADE), a phenomenon where antibodies bind a virion but fail to neutralize it and then the resultant antibody-virus complexes attach to Fc receptorbearing target cells (e.g., monocytes and macrophages), thereby increasing infection of such cells. Such a phenomenon has been observed in vitro for many viruses, perhaps most notably dengue virus (18,19) and also Zika virus (20,21), coronavirus (22), Ebola virus (23), and coxsackievirus B (24). In the case of dengue virus, an FcgRIIa polymorphism was shown to be significantly associated with dengue disease (versus subclinical infection); moreover, compelling evidence was recently published to support that ADE enhances disease severity in humans (25).…”

Section: Discussionmentioning

confidence: 93%

Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial

Gilbert

Carpp

et al. 2019

J Virol

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HIV Vaccine Trials Network (HVTN) 505 was a phase 2b efficacy trial of a DNA/recombinant adenovirus 5 (rAd5) HIV vaccine regimen. Although the trial was stopped early for lack of overall efficacy, later correlates of risk and sieve analyses generated the hypothesis that the DNA/rAd5 vaccine regimen protected some vaccinees from HIV infection yet enhanced HIV infection risk for others. Here, we assessed whether and how host Fc gamma receptor (Fc␥R) genetic variations influenced the DNA/rAd5 vaccine regimen's effect on HIV infection risk. We found that vaccine receipt significantly increased HIV acquisition compared with placebo receipt among participants carrying the FCGR2C-TATA haplotype (comprising minor alleles of four FCGR2C single-nucleotide polymorphism [SNP] sites) (hazard ratio [HR] ϭ 9.79, P ϭ 0.035) but not among participants without the haplotype (HR ϭ 0.86, P ϭ 0.67); the interaction of vaccine and haplotype effect was significant (P ϭ 0.034). Similarly, vaccine receipt increased HIV acquisition compared with placebo receipt among participants carrying the FCGR3B-AGA haplotype (comprising minor alleles of the 3 FCGR3B SNPs) (HR ϭ 2.78, P ϭ 0.058) but not among participants without the haplotype (HR ϭ 0.73, P ϭ 0.44); again, the interaction of vaccine and haplotype was significant (P ϭ 0.047). The FCGR3B-AGA haplotype also influenced whether a combined Env-specific CD8 ϩ T-cell polyfunctionality score and IgG response correlated significantly with HIV risk; an FCGR2A SNP and two FCGR2B SNPs influenced whether anti-gp140 antibody-dependent cellular phagocytosis correlated significantly with HIV risk. These results provide further evidence that Fc gamma receptor genetic variations may modulate HIV vaccine effects and immune function after HIV vaccination.

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“…Dengue virus re-infection can lead to antibodyenhanced disease by a mechanism that is associated with serologic cross-reactivity between different dengue serotypes (40)(41)(42). Antibodies to dengue also cross-react with ZIKV and experiments in mice and with human placental explants have shown that ZIKV infection can be enhanced by antibodies in these systems (43)(44)(45)(46). Conversely, antibodies to ZIKV that are maternally acquired cause more severe disease in mice infected with dengue (47).…”

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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Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages

Cited by 112 publications

References 61 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

Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial

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

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