scholarly journals Zika Virus Infection at Different Pregnancy Stages: Anatomopathological Findings, Target Cells and Viral Persistence in Placental Tissues

2018 ◽  
Author(s):  
Lucia de Noronha ◽  
Camila Zanluca ◽  
Marion Burger ◽  
Andreia Akemi Suzukawa ◽  
Marina Azevedo ◽  
...  
Keyword(s):  
Zika Virus ◽  
Congenital Malformations ◽  
Acute Infection ◽  
Histological Finding ◽  
Placental Tissue ◽  
Cell Types ◽  
Target Cells ◽  
Third Trimester ◽  
Zikv Infection ◽  
Hofbauer Cells

ABSTRACTZika virus (ZIKV) infection in humans has been associated with congenital malformations and other neurological disorders, such as Guillain-Barré syndrome. The mechanism(s) of ZIKV intrauterine transmission, the cell types involved, the most vulnerable period of pregnancy for severe outcomes from infection and other physiopathological aspects remain unknown. In this study, we analyzed placental samples obtained at the time of delivery from a group of twenty-four women diagnosed with ZIKV infection during the first, second or third trimesters of pregnancy. Villous immaturity was the main histological finding in the placental tissues, although placentas without alterations were also frequently observed. Significant enhancement of the number of syncytial sprouts was observed in the placentas of women infected during the third trimester, indicating the development of placental abnormalities after ZIKV infection. Hyperplasia of Hofbauer cells (HCs) was also observed in these third-trimester placental tissues, and remarkably, HCs were the only ZIKV-positive fetal cells found in the placentas studied that persisted until birth, as revealed by immunohistochemical (IHC) analysis. Thirty-three percent of women infected during pregnancy delivered infants with congenital abnormalities, although no pattern correlating the gestational stage at infection, the IHC positivity of HCs in placental tissues and the presence of congenital malformations at birth was observed. Placental tissue analysis enabled us to confirm maternal ZIKV infection in cases where serum from the acute infection phase was not available, which reinforces the importance of this technique in identifying possible causal factors of birth defects. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of some aspects of the pathophysiology of ZIKV.

scholarly journals Trimester-specific Zika virus infection affects placental responses in women

2019 ◽  
Author(s):  
Fok-Moon Lum ◽  
Vipin Narang ◽  
Susan Hue ◽  
Jie Chen ◽  
Naomi McGovern ◽  
...  
Keyword(s):  
Birth Defects ◽  
Zika Virus ◽  
Cellular Response ◽  
Prenatal Screening ◽  
Acute Infection ◽  
Transcriptomic Analysis ◽  
Placental Development ◽  
Zikv Infection ◽  
Hofbauer Cells ◽  
Screening Procedures

AbstractZika virus (ZIKV) infection during pregnancy is associated with neurologic birth defects, but the effects on placental development are unclear. Full-term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. In this study, each woman exhibited a unique immune response, but they collectively diverged from healthy controls with raised IL-1RA, IP-10, EGF and RANTES expression, and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co-localized to placental Hofbauer cells, the placentas showed no anatomical defects. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centered on differential eIF2 signaling, mitochondrial dysfunction and oxidative phosphorylation. These findings should translate to improve clinical prenatal screening procedures for virus-infected pregnant patients.

scholarly journals Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 91
Author(s):  
Verena Schultz ◽  
Stephanie L. Cumberworth ◽  
Quan Gu ◽  
Natasha Johnson ◽  
Claire L. Donald ◽  
...  
Keyword(s):  
Nervous System ◽  
Neural Development ◽  
Zika Virus ◽  
Developmental Stages ◽  
Cell Types ◽  
Neural Cells ◽  
Zikv Infection ◽  
Axonal Pathology ◽  
Time Frames

Understanding how Zika virus (Flaviviridae; ZIKV) affects neural cells is paramount in comprehending pathologies associated with infection. Whilst the effects of ZIKV in neural development are well documented, impact on the adult nervous system remains obscure. Here, we investigated the effects of ZIKV infection in established mature myelinated central nervous system (CNS) cultures. Infection incurred damage to myelinated fibers, with ZIKV-positive cells appearing when myelin damage was first detected as well as axonal pathology, suggesting the latter was a consequence of oligodendroglia infection. Transcriptome analysis revealed host factors that were upregulated during ZIKV infection. One such factor, CCL5, was validated in vitro as inhibiting myelination. Transferred UV-inactivated media from infected cultures did not damage myelin and axons, suggesting that viral replication is necessary to induce the observed effects. These data show that ZIKV infection affects CNS cells even after myelination—which is critical for saltatory conduction and neuronal function—has taken place. Understanding the targets of this virus across developmental stages including the mature CNS, and the subsequent effects of infection of cell types, is necessary to understand effective time frames for therapeutic intervention.

scholarly journals Distinct cellular immune signatures in acute Zika virus infection are associated with high or low persisting neutralizing antibody titers

2021 ◽  
Author(s):  
Elizabeth E. McCarthy ◽  
Pamela M. Odorizzi ◽  
Emma Lutz ◽  
Carolyn P. Smullin ◽  
Iliana Tenvooren ◽  
...  
Keyword(s):  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Immune Cell ◽  
Acute Infection ◽  
Neutralizing Antibody ◽  
Natural Immunity ◽  
Zikv Infection ◽  
Antibody Titers ◽  
Cellular Immune

Although the formation of a durable neutralizing antibody response after an acute viral infection is a key component of protective immunity, little is known about why some individuals generate high versus low neutralizing antibody titers to infection or vaccination. Infection with Zika virus (ZIKV) during pregnancy can cause devastating fetal outcomes, and efforts to understand natural immunity to this infection are essential for optimizing vaccine design. In this study, we leveraged the high-dimensional single-cell profiling capacity of mass cytometry (CyTOF) to deeply characterize the cellular immune response to acute and convalescent ZIKV infection in a cohort of blood donors in Puerto Rico incidentally found to be viremic during the 2015-2016 epidemic in the Americas. During acute ZIKV infection, we identified widely coordinated responses across innate and adaptive immune cell lineages. High frequencies of multiple activated innate immune subsets, as well as activated follicular helper CD4+ T cells and proliferating CD27-IgD- B cells, during acute infection were associated with high titers of ZIKV neutralizing antibodies at 6 months post-infection. On the other hand, low titers of ZIKV neutralizing antibodies were associated with immune features that suggested a cytotoxic-skewed immune "set-point." Our study offers insight into the cellular coordination of immune responses and identifies candidate cellular biomarkers that may offer predictive value in vaccine efficacy trials for ZIKV and other acute viral infections aimed at inducing high titers of neutralizing antibodies.

scholarly journals Pregnancy and Zika virus

2020 ◽  
Vol 14 (2) ◽  
pp. 229-238
Author(s):  
T. V. Startseva ◽  
N. N. Kanshina ◽  
M. V. Tretyakova ◽  
V. O. Bitsadze ◽  
J. Kh. Khizroeva ◽  
...  
Keyword(s):  
Nonhuman Primate ◽  
Zika Virus ◽  
Congenital Malformations ◽  
Asymptomatic Carrier ◽  
Clinical Signs ◽  
Neurological Complications ◽  
Zikv Infection ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
Urban Cycle

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the genus Flavivirus and the Flaviviridae family. In 1947 and 1948 ZIKV was first isolated from a nonhuman primate as well as from mosquitoes in Africa, respectively. For half a century, ZIKV infections in human were sporadic prior to 2015–2016 pandemic spreading. Transmission of ZIKV from mother to fetus can occur in any trimester of pregnancy, even if mother was an asymptomatic carrier. The clinical signs of ZIKV infection are nonspecific and can be misdiagnosed as some other infectious diseases, especially those caused by arboviruses such as Dengue and Chikungunya. ZIKV infection was solely associated with mild illness prior to the large French Polynesian and Brazil outbreaks, when severe neurological complications, Guillain–Barre syndrome and dramatically increased rate of severe congenital malformations (including microcephaly) were reported. The adaptation of ZIKV to an urban cycle in endemic areas suggests that the incidence of ZIKV infections may be underestimated. The pandemic of novel coronavirus infection (COVID-19) demonstrates that lessons from ZIKV pandemic propagation has not been learned properly.

scholarly journals Animal Models of Zika Virus Infection, Pathogenesis, and Immunity

2017 ◽  
Vol 91 (8) ◽  
Author(s):  
Thomas E. Morrison ◽  
Michael S. Diamond
Keyword(s):  
Animal Models ◽  
Virus Infection ◽  
Zika Virus ◽  
Congenital Malformations ◽  
Scientific Community ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Rapid Testing ◽  
Zikv Infection ◽  
Male Reproductive Tract

ABSTRACT Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis.

scholarly journals Zika Virus Infects Human Placental Mast Cells and the HMC-1 Cell Line, and Triggers Degranulation, Cytokine Release and Ultrastructural Changes

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 975 ◽  
Author(s):  
Kíssila Rabelo ◽  
Antônio José da Silva Gonçalves ◽  
Luiz José de Souza ◽  
Anna Paula Sales ◽  
Sheila Maria Barbosa de Lima ◽  
...  
Keyword(s):  
Mast Cells ◽  
Cell Line ◽  
Zika Virus ◽  
Post Infection ◽  
Immune Cell ◽  
Cell Types ◽  
Ultrastructural Changes ◽  
Congenital Defects ◽  
Zikv Infection ◽  
Intracellular Changes

Zika virus (ZIKV) is an emergent arthropod-borne virus whose outbreak in Brazil has brought major public health problems. Infected individuals have different symptoms, including rash and pruritus, which can be relieved by the administration of antiallergics. In the case of pregnant women, ZIKV can cross the placenta and infect the fetus leading to congenital defects. We have identified that mast cells in the placentae of patients who had Zika during pregnancy can be infected. This led to our investigation on the possible role of mast cells during a ZIKV infection, using the HMC-1 cell line. We analyzed their permissiveness to infection, release of mediators and ultrastructural changes. Flow cytometry detection of ZIKV-NS1 expression 24 h post infection in 45.3% of cells showed that HMC-1 cells are permissive to ZIKV infection. Following infection, β-hexosaminidase was measured in the supernatant of the cells with a notable release at 30 min. In addition, an increase in TNF-α, IL-6, IL-10 and VEGF levels were measured at 6 h and 24 h post infection. Lastly, different intracellular changes were observed in an ultrastructural analysis of infected cells. Our findings suggest that mast cells may represent an important source of mediators that can activate other immune cell types during a ZIKV infection, which has the potential to be a major contributor in the spread of the virus in cases of vertical transmission.

scholarly journals Cell-specific characterization of the placental methylome

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria S. Peñaherrera ◽  
Alexander G. Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n = 9) and term (n = 19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at > 850,000 CpGs. Results The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation. Conclusions Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from GEO (GSE159526), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

scholarly journals Zika virus infection of the placenta alters extracellular matrix proteome

2021 ◽  
Author(s):  
Gabriel Borges-Vélez ◽  
Julio Rosado-Philippi ◽  
Yadira M. Cantres-Rosario ◽  
Kelvin Carrasquillo-Carrion ◽  
Abiel Roche-Lima ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Zika Virus ◽  
Placental Tissue ◽  
Zikv Infection ◽  
Ecm Proteins ◽  
Label Reagent ◽  
Tandem Mass Tag ◽  
Mass Spectrometry Identification ◽  
Proteome Discoverer ◽  
Cellular Components

AbstractZika virus (ZIKV) infection has been associated with fetal abnormalities by compromising placental integrity, but the mechanisms by which this occurs are unknown. Flavivirus can deregulate the host proteome, especially extracellular matrix (ECM) proteins. We hypothesize that a deregulation of specific ECM proteins by ZIKV, affects placental integrity. Using twelve different placental samples collected during the 2016 ZIKV Puerto Rico epidemic, we compared the proteome of five ZIKV infected samples with four uninfected controls followed by validation of most significant proteins by immunohistochemistry. Quantitative proteomics was performed using tandem mass tag TMT10plex™ Isobaric Label Reagent Set followed by Q Exactive™ Hybrid Quadrupole Orbitrap Mass Spectrometry. Identification of proteins was performed using Proteome Discoverer 2.1. Proteins were compared based on the fold change and p value using Limma software. Significant proteins pathways were analyzed using Ingenuity Pathway (IPA). TMT analysis showed that ZIKV infected placentas had 94 reviewed differentially abundant proteins, 32 more abundant, and 62 less abundant. IPA analysis results indicate that 45 of the deregulated proteins are cellular components of the ECM and 16 play a role in its structure and organization. Among the most significant proteins in ZIKV positive placenta were fibronectin, bone marrow proteoglycan, and fibrinogen. Of these, fibrinogen was further validated by immunohistochemistry in 12 additional placenta samples and found significantly increased in ZIKV infected placentas. The upregulation of this protein in the placental tissue suggests that ZIKV infection is promoting the coagulation of placental tissue and restructuration of ECM potentially affecting the integrity of the tissue and facilitating dissemination of the virus from mother to the fetus.

scholarly journals Human neutrophils are not activated by Zika virus but reduce the infection of susceptible cells

2021 ◽  
Author(s):  
Juliana Bernardi Aggio ◽  
Bárbara Nery Porto ◽  
Claudia Nunes Duarte dos Santos ◽  
Ana Luiza Pamplona Mosimann ◽  
Pryscilla Fanini Wowk
Keyword(s):  
Zika Virus ◽  
Neutrophil Migration ◽  
A549 Cells ◽  
Human Neutrophils ◽  
Cell Contact ◽  
Target Cells ◽  
Zikv Infection ◽  
Host Interaction

Zika virus (ZIKV) emergence highlighted the need for a deeper understanding on virus-host interaction to pave the development of antiviral therapies. The present work aimed to address the response of neutrophils during ZIKV infection. Neutrophils are an important effector cell in innate immunity involved in the host response to neurotropic arboviruses. Our results indicate that human neutrophils were not permissive to Asian or African ZIKV strains replication. Indeed, after stimulation with ZIKV, neutrophils were not primed against the virus as evaluated by the absence of CD11b modulation, secretion of inflammatory cytokines and granule content, production of reactive oxygen species and neutrophil extracellular traps formation. Overall, neutrophils did not affect ZIKV infectivity. Moreover, ZIKV infection of primary innate immune cells in vitro did not trigger neutrophil migration. However, neutrophil co-cultured with ZIKV susceptible cells (A549) resulted in lower frequencies of infection on A549 cells by cell-to-cell contact. In vivo, neutrophil depletion from immunocompetent mice did not affect ZIKV spreading to the draining lymph nodes. The data suggest human neutrophils do not play a per se antiviral role against ZIKV, but these cells might participate in an infected environment shaping the ZIKV infection in other target cells.

scholarly journals Zika Virus

2020 ◽  
Author(s):  
Marciano Paes ◽  
Kíssila Rabelo
Keyword(s):  
Mast Cells ◽  
Zika Virus ◽  
Post Infection ◽  
Immune Cell ◽  
Cell Types ◽  
Ultrastructural Changes ◽  
Congenital Defects ◽  
Zikv Infection ◽  
Flow Cytometry Detection ◽  
Intracellular Changes

Zika virus (ZIKV) is an emergent arthropod-borne virus whose outbreak in Brazil has brought major public health problems. Infected individuals have different symptoms, including rash and pruritus, which can be relieved by the administration of antiallergics. In the case of pregnant women, ZIKV can cross the placenta and infect the fetus leading to congenital defects. We have identified that mast cells in the placentae of patients who had Zika during pregnancy can be infected. This led to our investigation on the possible role of mast cells during a ZIKV infection, using the HMC-1 cell line. We analyzed their permissiveness to infection, release of mediators and ultrastructural changes. Flow cytometry detection of ZIKV-NS1 expression 24h post infection in 45.3% of cells showed that HMC-1 cells are permissive to ZIKV infection. Following infection, β-hexosaminidase was measured in the supernatant of the cells with a notable release at 30 min. In addition, an increase in TNF-α, IL-6, IL-10 and VEGF levels were measured at 6h and 24h post infection. Lastly, different intracellular changes were observed in an ultrastructural analysis of infected cells. Our findings suggest that mast cells may represent an important source of mediators that can activate other immune cell types during a ZIKV infection, which has the potential to being a major contributor in the spread of the virus in cases of vertical transmission.

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