Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Male Germ Cells Support Long-Term Propagation of Zika Virus

ABSTRACT: Evidence of male-to-female sexual transmission of Zika virus (ZIKV) and viral RNA in semen and sperm months after infection support a potential role for testicular cells in ZIKV propagation. Here, we demonstrate that germ cells (GC) are most susceptible to ZIKV. We find that only GC infected by ZIKV, but not those infected by dengue fever (DENV) and yellow fever virus (YFV), produce high levels of infectious virus. This observation coincides with decreased expression of interferon-stimulated gene Ifi44l in ZIKV-infected GC and over-expression of Ifi44l results in reduced ZIKV production. Using primary human testicular tissue, we demonstrate that human GC are also permissive for ZIKV infection and production. Finally, we identify berberine chloride as a potent inhibitor of ZIKV infection in both murine and human testes. Together, these studies identify a potential cellular source for propagation of ZIKV in testes and a candidate drug for preventing sexual transmission of ZIKV.

ORGANISM(S): Mus musculus

PROVIDER: GSE113177 | GEO | 2018/06/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Paracrine IFN response limits ZIKV infection in human Sertoli cells

Project description:Zika virus (ZIKV) is unique among mosquito-borne flaviviruses in its ability to be sexually transmitted. The testes have been implicated as sites of long-term ZIKV replication, and our previous studies have identified Sertoli cells (SC), the nurse cells of the seminiferous epithelium that govern spermatogenesis, as major targets of ZIKV infection. To improve our understanding of the host-ZIKV interaction within human testicular cells, we analyzed ZIKV-induced proteome changes in SC and mixed seminiferous tubule cells (STC) using high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS). We found that ZIKV infection in SC and STC induced distinct IFN-stimulated proteins and impacted pathways and functional networks associated with innate antiviral defense. IFN signaling was the most significantly enriched pathway and MX1 was the most abundant IFN-stimulated protein in both SC and STC. Increased levels of MX1 at later time points of infection coincided with diminished propagation of ZIKV in SC, whereas silencing of MX1 and IFIT1 enhanced peak ZIKV titers in SC. Furthermore, although downstream IFN-I signaling was found to be functional and restricted ZIKV replication in SC, in comparison to A549 cells, SC exhibited dampened expression of IFN-I/III-stimulated genes despite higher levels of virus progeny and IFN-I/III transcripts. Together, this study highlights the IFN-I/III response as a driver of the antiviral state that limits ZIKV infection in SC and suggests that delayed and reduced robustness of innate antiviral defense in SC may contribute to ZIKV persistence in the testes.

2021-09-10 | PXD025133 | Pride

Novel Model for Vertical Zika Virus Transmission via Decidual Cell-mediated Infection of Anchoring Villi

Project description:Vertical transmission of Zika virus (ZIKV) causes severe fetal defects, but the exact pathogenic mechanism is unclear. We identified up to a 10480-fold higher expression of viral attachment factors AXL, GAS6 and PROS1 and 3880-fold increase in ZIKV infectiousness/propagation in decidual cells (DCs) versus trophoblasts. Moreover, levels of viral attachment factors and ZIKV are significantly increased while expression of innate immune response genes are significantly decreased in first trimester versus term DCs. ZIKV-infected DC supernatants increased cytotrophoblast infection up to 252-fold compared to directly infected cytotrophoblasts. Tizoxanide treatment efficiently inhibited ZIKV infection in both cell types. We conclude that decidual cells may act as reservoirs for trimester-dependent placental transmission of ZIKV, accounting for the higher ZIKV infection susceptibility and more severe fetal sequelae observed in early versus late pregnancy. Moreover, tizoxanide is a promising agent in preventing perinatal ZIKV transmission.

2020-03-14 | GSE146980 | GEO

RNA sequencing of Aedes mosquitoes infected with Zika virus (ZIKV) or Dengue virus (DENV)

Project description:Zika virus (ZIKV), a pathogen of global health concern, is transmitted to humans by Aedes mosquitoes. However, the molecular interactions between the vector and the virus remain largely unexplored. We demonstrated that ZIKV and dengue virus (DENV) have similar tropism and infection kinetics in two mosquito strains with different degrees of susceptibility to infection. Comparison of Aedes aegypti’s molecular responses to ZIKV and DENV infection indicated that around 40% of the mosquito’s infection-responsive transcriptome is virus-specific. Regulated genes also included key factors of the mosquito’s anti-viral immunity, pointing to the possible involvement of the Toll innate immune pathway. Comparison of ZIKV and DENV infection-responsive transcriptome data to those for yellow fever virus and West Nile virus identified 26 genes likely to play key roles in virus infection of Aedes mosquitoes. Through reverse genetic analyses, we showed that the Toll and the Jak/Stat innate immune pathways mediate increased resistance to ZIKV infection, and the virus use vATPase and inosine-5’-monophosphate dehydrogenase as mosquito’s host factors.

2017-11-07 | GSE96605 | GEO

Effects of Zika virus infection on the metabolome of pregnant women: a longitudinal study

Project description:Zika virus (ZIKV) is a mosquito-borne +ssRNA virus that can cause abnormal development in human fetal central neuron system and even lead to stillbirth. Despite the popularity of studies in this area recently, there is currently still no sufficient treatment for it. Knowledge on how ZIKV infection impact human metabolisms is still lacking. Untargeted metabolomics can profile the overall change in metabolites after infection, thus provide hypothesis for specific investigations. We here performed a Nuclear Magnetic Resonance spectroscopy (NMR)-based untargeted case-control metabolomics study on urine of ZIKV-infected pregnant women. We collected samples monthly from the first trimester till up to 6 months of ZIKV-infected and non-infected individuals and modelled the longitudinal data. We identified 3-aminoisobutyrate and trigonelline with significantly higher levels in the ZIKV-infected patients, while 11 metabolites (fucose, 2-hydroxyglutarate, N-acetyl-glutamine, dimethylamine, 4-hydroxyphenethyl alcohol, creatinine, lactate, threonine, histidine, pseudouridine, and 1-methylnicotinamide) had significantly lower levels. We also identified 2 metabolites, including glucose and 1-methylnicotinamide, where the trends over time of the intensity levels between the two groups were significantly different. These metabolites suggested further study on tryptophan, NAD+, pyrimidine, and glucose metabolisms. These metabolomic changes may lead us to a better understanding of mechanisms that cause poor fetal outcomes as well as effects of virus infection on human pregnancy.

2022-01-03 | ST002048 | MetabolomicsWorkbench

Molecular Signatures Associated with ZIKV Exposure in Human Cortical Neural Progenitors and Astrocytes

Project description:Zika virus (ZIKV) infection causes microcephaly and has been linked to other brain abnormalities. How ZIKV impairs brain development and function remains elusive. Here we systematically profiled transcriptomes of human neural progenitor cells (hNPCs) and astrocytes exposed to Asian ZIKVC, African ZIKVM, and Dengue virus (DENV). DENV causes distinct gene expression changes; and ZIKV has a broader impact on the expression of gene involved in DNA replication and repair. While overall expression profiles are similar, ZIKVC, but not ZIKVM, induces upregulation of viral response genes. Upon ZIKV infection, astrocytes exhibit more prominent transcriptome changes than hNPCs, particularly enriching genes related to inflammatory response and cytokine production pathways. Our analyses reveal cell-type- and strain-specific molecular signatures associated with ZIKV infection, and identify astrocytes as a major direct target of ZIKV. Further investigation of ZIKV-host interactions based our transcriptomic datasets may help to illuminate neural virulence determinants of ZIKV in patients. Gene Expression Analyses of the cells infected with different flaviviruses

2016-08-23 | E-GEOD-80434 | biostudies-arrayexpress

Identification of AGO-associated viral interfering RNAs in Zika virus infected neural stem cells

Project description:Viral interfering RNA (viRNA) has been identified from several viral genomes via directly deep RNA sequencing of the virus-infected cells, including zika virus (ZIKV). Once produced by endoribonuclease Dicer, viRNAs, similar to microRNAs, are loaded onto Argonaute (AGO) family proteins of the RNA-induced silencing complexes (RISCs) to pair with their RNA targets and then initiate cleavage of the target genes. However, identities of functional ZIKV viRNAs and their viral RNA targets remain largely unknown. By combining AGO-associated RNA sequencing, deep sequencing analysis in ZIKV-infected neural stem cells (NSCs), and miRanda target scanning, we have defined 29 ZIKV derived viRNA profiles in NSCs, and established the complex interaction networks between the viRNAs and their viral targets. Our recent study has shown that ZIKV capsid protein interacted with Dicer and antagonized its endoribonuclease activity depending on its histidine (H) at the 41st amino acid. Accordingly, the rescued ZIKV-H41R mutant virus, compared to wild-type ZIKV, no longer suppressed Dicer enzymatic activity and consequently failed to inhibit miRNA biogenesis in NSCs. As a result, much higher levels of viRNAs generated from the ZIKV-H41R virus-infected NSCs, suggesting Dicer-dependent viRNA production. Knockdown of individual RNAi machinery in ZIKV-infected NSCs suggests that viRNA is a limiting factor of ZIKV infection in NSCs. The mapping of viRNAs to their RNA targets is paving a way to further investigate how viRNAs play the role in anti-viral mechanisms or even other unknown biological functions.

2021-02-16 | GSE159916 | GEO

The expression profile of miRNA in the testis of STZ-induced diabetic rats

Project description:The number of patients with diabetes is increasing worldwide. Diabetic testicular damage can cause spermiogenesis disorders and sexual dysfunction. We thus explored the role of miRNAs in diabetic testicular damage, and revealed that they could serve as effective prevention and treatment therapeutic targets.Streptozotocin (STZ) was used to generate a rat model of type 2 diabetes. Rat testicular tissues were used for miRNA sequencing. we identified 19 differentially expressed miRNAs in the testes of diabetic rats.

2021-03-05 | GSE168267 | GEO

Glioblastoma stem cells infected by ZIKA virus

Project description:We repoted the Glioblastoma stem cells(GSCs) infected by two strains of ZIKA virus, the Brazil and Dakar strains. The ZIKV was added into the medium of GSCs for 48 hours, the RNA was harvested after ZIKV infection. We found that the GSCs up-regulated the Type 1&2 interferons after infected by ZIKV

2017-08-23 | GSE102924 | GEO

Effect of ZIKV on pre-implantation embryos

Project description:To determine the effect of Zika virus infection on pre-implantation embryonic development, we performed single blastocyst RNA-Seq on MOCK and ZIKV infected embryos. ZIKV infection results in an increased risk of spontaneous abortion and poor intrauterine growth although the mechanisms underlying fetal loss remain undetermined. Little is known about the impact of ZIKV infection during the earliest stages of pregnancy, or pre- and peri-implantation, because most current studies of ZIKV infection in pregnancy models focus on post-implantation stages. Here, we demonstrate that trophectoderm cells of pre-implantation human and mouse embryos can be efficiently infected with ZIKV, and that trophectoderm can propagate virus causing cell death of neural progenitors. These findings were corroborated by our demonstration that hESC-derived trophectoderm cells are infected by ZIKV in a dose dependent manner. RNAseq of single blastocysts revealed key transcriptional changes in cellular and physiologic functions upon ZIKV infection, including nervous system development and function, prior to commitment to the neural cell lineage. Finally, the pregnancy rate of mice infected pre-implantation was > 50% lower than females infected at E4.5. These results demonstrate that pre-implantation ZIKV infection of trophectoderm leads to miscarriage or spontaneous abortion. Moreover, pre- and peri-implantation ZIKV infects trophectoderm cells that propagate virus over time causing cell death in neural progenitors. Cumulatively, these data demonstrate that vertical pre- and peri-implantation ZIKV infection of trophectoderm impairs fetal development and causes neural progenitor cell death, elucidating a previously unappreciated association of pre- and peri-implantation ZIKV infection and microcephaly.

2019-08-16 | GSE133254 | GEO

RNA-seq of embryonic fibroblasts cell lines derived from CC001, CC071 and C57BL/6J mouse strains infected with ZIKV virus

Project description:Embryonic fibroblasts cell lines derived from CC001, CC071 and C57BL/6J mouse strains were infected with ZIKV virus.

2023-09-06 | E-MTAB-12765 | biostudies-arrayexpress