Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA927006 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23209465_1.fastq.gz | Fastqsanger.gz | |||
| SRR23209465_2.fastq.gz | Fastqsanger.gz | |||
| SRR23209466_1.fastq.gz | Fastqsanger.gz | |||
| SRR23209466_2.fastq.gz | Fastqsanger.gz | |||
| SRR23209467_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 64 |
Similar Datasets
Project description:The female reproductive tract (FRT) is vulnerable to sexually transmitted infections and therefore a well-tuned immune surveillance system is crucial for maintaining a healthy FRT. However, our understanding of the factors that impact viral infection of the FRT and the host response are not well understood. In this work, we investigate the role of a hormonally regulated type I interferon, IFN epsilon, in control of Zika virus (ZIKV) infection of the FRT. We demonstrate that IFN epsilon has anti-ZIKV properties using a combination of IFN epsilon KO mice, blockade of endogenous IFN epsilon by neutralising Abs and rescue of IFN epsilon KO mice by recombinant IFN epsilon administered directly to the FRT.
2023-02-14 | GSE223635 | GEO
Project description:The immunological surveillance factors controlling vulnerability of the female reproductive tract (FRT) to sexually transmitted viral infections are not well understood. Interferon-epsilon (IFNɛ) is a distinct, immunoregulatory type-I IFN that is constitutively expressed by FRT epithelium and is not induced by pathogens like other antiviral IFNs α, β and λ. We show the necessity of IFNɛ for Zika Virus (ZIKV) protection by: increased susceptibility of IFNɛ-/- mice; their "rescue" by intravaginal recombinant IFNɛ treatment and blockade of protective endogenous IFNɛ by neutralising antibody. Complementary studies in human FRT cell lines showed IFNɛ had potent anti-ZIKV activity, associated with transcriptome responses similar to IFNλ but lacking the proinflammatory gene signature of IFNα. IFNɛ activated STAT1/2 pathways similar to IFNα and λ that were inhibited by ZIKV-encoded non-structural (NS) proteins, but not if IFNε exposure preceded infection. This scenario is provided by the constitutive expression of endogenous IFNε. However, the IFNɛ expression was not inhibited by ZIKV NS proteins despite their ability to antagonise the expression of IFNβ or λ. Thus, the constitutive expression of IFNɛ provides cellular resistance to viral strategies of antagonism and maximises the antiviral activity of the FRT. These results show that the unique spatiotemporal properties of IFNε provides an innate immune surveillance network in the FRT that is a significant barrier to viral infection with important implications for prevention and therapy.
| S-EPMC10032502 | biostudies-literature
Project description:Interferon ε (IFNε), a unique type I IFN, is thought to protect the host against sexually transmitted infections. Unlike conventional type I IFNs (e.g., IFNα/β), whose expression is undetectable at baseline, IFNε expression is detectable in the epithelium of mucosal tissues, particularly the female reproductive tract (FRT). We found that IFNε expression was not limited to epithelial cells at the FRT. Importantly, in contrast to previous reports, IFNε expression in plasmacytoid dendritic cells and primary cervical epithelial cells was induced by viral infection and by activation of TLR3 or 4 in PBMCs. Induction of IFNε mRNAs was also found in cervicovaginal tissues (CVT) of Zika virus (ZIKV)-infected mice. Mice with IFNε deficiency (Ifnε-/-) did not have impaired induction of interferon-stimulated genes except IFNl, but had altered epithelial and collagen structure in the CVT. Ifnε-/- mice exhibited increased susceptibility to ZIKV infection via an intravaginal route but not via a subcutaneous route, indicating that the protective effect of IFNe was specific to the FRT. Infected Ifnε-/- mice had higher and more sustained viral loads than infected wild-type (WT) mice. Detection of ZIKV infection by single molecule in situ hybridization confirmed that virus spread faster in Ifnε-/- mice than in WT mice. Recombinant murine IFNε protected Ifnar1-/- mice against ZIKV infection when administered through an intravaginal route but not when administered through a subcutaneous route, indicating that the specific role of IFNe at the FRT is independent of IFNAR1 signaling. Our findings indicate that IFNε mediates a novel FRT-specific protective effect on mucosal immunity that limits Zika virus spread.
2023-05-11 | GSE228359 | GEO
Project description:Interferon ε (IFNε) is a unique type I IFN that has been implicated in host defense against sexually transmitted infections (STIs). Zika virus (ZIKV), an emerging pathogen, can infect the female reproductive tract (FRT) and cause devastating diseases, particularly in pregnant women. How IFNε contributes to protection against ZIKV infection in vivo is unknown. Here, we show that IFNε plays a critical role in host protection against vaginal ZIKV infection in mice. We found that IFNε was expressed not only by epithelial cells in the FRT, but also by certain immune and other cells at baseline or after exposure to viruses or specific TLR agonists. IFNε-deficient mice exhibited abnormalities in the epithelial border and underlying tissue in the cervicovaginal tract, and these defects were associated with increased susceptibility to vaginal, but not subcutaneous ZIKV infection. IFNε-deficiency resulted in an increase in magnitude, duration, and depth of ZIKV infection in the FRT. Critically, intravaginal administration of recombinant IFNε protected Ifnε-/- mice and highly susceptible Ifnar1-/- mice against vaginal ZIKV infection, indicating that IFNε was sufficient to provide protection even in the absence of signals from other type I IFNs and in an IFNAR1-independent manner. Our findings reveal a potentially critical role for IFNε in mediating protection against transmission of ZIKV in the context of sexual contact.
| S-EPMC10104157 | biostudies-literature
Project description:Interferon e restricts Zika infection at the female reproductive tract
| PRJNA949554 | ENA
Project description:Zika virus (ZIKV) can cause devastating effects in the unborn fetus of pregnant women. To develop a candidate vaccine that can protect human fetuses, we generated a panel of live measles vaccine (MV) vectors expressing ZIKV-E and -NS1. Our MV-based ZIKV-E vaccine, MV-E2, protected mice from the non-lethal Zika Asian strain (PRVABC59) and the lethal African strain (MR766) challenge. Despite 100% survival of the MV-E2 mice, however, complete viral clearance was not achieved in the brain and reproductive tract of the lethally challenged mice. We then tested MV-based vaccines that expressed E and NS1 together or separately in two different vaccines. We observed complete clearance of ZIKV from the female reproductive tract and complete fetal protection in the lethal African challenge model in animals that received the dual antigen vaccines. Additionally, MV-E2 and MV-NS1, when administered together, induced durable plasma cell responses. Our findings suggest that NS1 antibodies are required to enhance the protection of ZIKV-E antibodies in the female reproductive tract.
| S-EPMC9018676 | biostudies-literature
Project description:To better understand the critical drivers of Zika virus pathogenicity, we used microarray analysis to evaluate the host responses triggered by Zika virus infection in MRC-5 cells.
2021-03-23 | E-MTAB-10292 | biostudies-arrayexpress
Project description:RNA-seq count data at 3 timepoints was generated for Zika-exposed and Zika-naïve individuals in order to assess associated signatures
2019-04-17 | GSE129882 | GEO
Project description:Sexual transmission of Zika virus (ZIKV) is a matter of great concern. Infectious viral particles can be shed in semen for as long as six months after infection and can be transferred to male and female sexual partners during unprotected sexual intercourse. The virus can be found inside spermatozoa and could be directly transferred to the oocyte during fertilization. Sexual transmission of ZIKV can contribute to the rise in number of infected individuals in endemic areas as well as in countries where the mosquito vector does not thrive. There is also the possibility, as has been demonstrated in mouse models, that the vaginal deposition of ZIKV particles present in semen could lead to congenital syndrome. In this paper, we review the current literature to understand ZIKV trafficking from the bloodstream to the human male reproductive tract and viral interactions with host cells in interstitial spaces, tubule walls, annexed glands and semen. We hope to highlight gaps to be filled by future research and potential routes for vaccine and antiviral development.
| S-EPMC6027493 | biostudies-other