scholarly journals IFN-λ Decreases Murid Herpesvirus-4 Infection of the Olfactory Epithelium but Fails to Prevent Virus Reactivation in the Vaginal Mucosa

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 757 ◽  
Author(s):  
Sophie Jacobs ◽  
Caroline Zeippen ◽  
Fanny Wavreil ◽  
Laurent Gillet ◽  
Thomas Michiels
Keyword(s):  
B Cells ◽  
Epithelial Cells ◽  
Olfactory Epithelium ◽  
Genital Tract ◽  
Vaginal Mucosa ◽  
Virus Reactivation ◽  
Olfactory Neurons ◽  
Sustentacular Cells ◽  
Herpesvirus 4

Murid herpesvirus-4 (MuHV-4), a natural gammaherpesvirus of rodents, can infect the mouse through the nasal mucosa, where it targets sustentacular cells and olfactory neurons in the olfactory epithelium before it propagates to myeloid cells and then to B cells in lymphoid tissues. After establishment of latency in B cells, viral reactivation occurs in the genital tract in 80% of female mice, which can lead to spontaneous sexual transmission to co-housed males. Interferon-lambda (IFN-λ) is a key player of the innate immune response at mucosal surfaces and is believed to limit the transmission of numerous viruses by acting on epithelial cells. We used in vivo plasmid-mediated IFN-λ expression to assess whether IFN-λ could prophylactically limit MuHV-4 infection in the olfactory and vaginal mucosae. In vitro, IFN-λ decreased MuHV-4 infection in cells that overexpressed IFN-λ receptor 1 (IFNLR1). In vivo, prophylactic IFN-λ expression decreased infection of the olfactory epithelium but did not prevent virus propagation to downstream organs, such as the spleen where the virus establishes latency. In the olfactory epithelium, sustentacular cells readily responded to IFN-λ. In contrast, olfactory neurons did not respond to IFN-λ, thus, likely allowing viral entry. In the female genital tract, columnar epithelial cells strongly responded to IFN-λ, as did most vaginal epithelial cells, although with some variation from mouse to mouse. IFN-λ expression, however, failed to prevent virus reactivation in the vaginal mucosa. In conclusion, IFN-λ decreased MuHV-4 replication in the upper respiratory epithelium, likely by protecting the sustentacular epithelial cells, but it did not protect olfactory neurons and failed to block virus reactivation in the genital mucosa.

scholarly journals Antibodies to gp350/220 Enhance the Ability of Epstein-Barr Virus To Infect Epithelial Cells

2006 ◽  
Vol 80 (19) ◽  
pp. 9628-9633 ◽  
Author(s):  
Susan M. Turk ◽  
Ru Jiang ◽  
Liudmila S. Chesnokova ◽  
Lindsey M. Hutt-Fletcher
Keyword(s):  
B Cells ◽  
Nasopharyngeal Carcinoma ◽  
Epithelial Cells ◽  
Epstein Barr Virus ◽  
Lytic Cycle ◽  
Virus Envelope ◽  
Barr Virus ◽  
High Risk Populations ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) is a persistent, orally transmitted herpesvirus that replicates in B cells and epithelial cells and is associated with lymphoid and epithelial malignancies. The virus binds to CD21 on B cells via glycoprotein gp350/220 and infects efficiently. Infection of cultured epithelial cells has not typically been efficient but can occur in the absence of gp350/220 and CD21 and in vivo is thought to be important to the development of nasopharyngeal carcinoma. We report here that antibodies to gp350/220, which inhibit EBV infection of B cells, enhance infection of epithelial cells. The effect is not mediated by Fc receptor binding but is further enhanced by antibody cross-linking, which may patch gp350/220 in the virus envelope. Saliva from EBV-seropositive individuals has similar effects that can be reversed by depletion of antibody. The results are consistent with a model in which gp350/220 interferes with the access of other important players to the epithelial cell surface. The results may have implications for the development of nasopharyngeal carcinoma in high-risk populations in which elevated titers of antibody to EBV lytic cycle proteins are prognostic.

scholarly journals Mouse Model of Cervicovaginal Toxicity and Inflammation for Preclinical Evaluation of Topical Vaginal Microbicides

2004 ◽  
Vol 48 (5) ◽  
pp. 1837-1847 ◽  
Author(s):  
Bradley J. Catalone ◽  
Tina M. Kish-Catalone ◽  
Lynn R. Budgeon ◽  
Elizabeth B. Neely ◽  
Maelee Ferguson ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
In Vitro Cytotoxicity ◽  
Model Systems ◽  
Vaginal Mucosa ◽  
Minimal Damage ◽  
Hiv 1 ◽  
Topical Microbicide

ABSTRACT Clinical trials evaluating the efficacy of nonoxynol-9 (N-9) as a topical microbicide concluded that N-9 offers no in vivo protection against human immunodeficiency virus type 1 (HIV-1) infection, despite demonstrated in vitro inactivation of HIV-1 by N-9. These trials emphasize the need for better model systems to determine candidate microbicide effectiveness and safety in a preclinical setting. To that end, time-dependent in vitro cytotoxicity, as well as in vivo toxicity and inflammation, associated with N-9 exposure were characterized with the goal of validating a mouse model of microbicide toxicity. In vitro studies using submerged cell cultures indicated that human cervical epithelial cells were inherently more sensitive to N-9-mediated damage than human vaginal epithelial cells. These results correlated with in vivo findings obtained by using Swiss Webster mice in which intravaginal inoculation of 1% N-9 or Conceptrol gel (containing 4% N-9) resulted in selective and acute disruption of the cervical columnar epithelial cells 2 h postapplication accompanied by intense inflammatory infiltrates within the lamina propria. Although damage to the cervical epithelium was apparent out to 8 h postapplication, these tissues resembled control tissue by 24 h postapplication. In contrast, minimal damage and infiltration were associated with both short- and long-term exposure of the vaginal mucosa to either N-9 or Conceptrol. These analyses were extended to examine the relative toxicity of polyethylene hexamethylene biguanide (PEHMB), a polybiguanide compound under evaluation as a candidate topical microbicide. In similar studies, in vivo exposure to 1% PEHMB caused minimal damage and inflammation of the genital mucosa, a finding consistent with the demonstration that PEHMB was >350-fold less cytotoxic than N-9 in vitro. Collectively, these studies highlight the murine model of toxicity as a valuable tool for the preclinical assessment of toxicity and inflammation associated with exposure to candidate topical microbicides.

scholarly journals Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters

2020 ◽  
Author(s):  
Bertrand Bryche ◽  
Audrey St Albin ◽  
Severine Murri ◽  
Sandra Lacôte ◽  
Coralie Pulido ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lamina Propria ◽  
Olfactory Epithelium ◽  
Immune Cells ◽  
Olfactory Neurons ◽  
Syrian Hamsters ◽  
Sustentacular Cells ◽  
The Central Nervous System ◽  
The Impact

AbstractAnosmia is one of the most prevalent symptoms of SARS-CoV-2 infection during the COVID-19 pandemic. However, the cellular mechanism behind the sudden loss of smell has not yet been investigated. The initial step of odour detection takes place in the pseudostratified olfactory epithelium (OE) mainly composed of olfactory sensory neurons surrounded by supporting cells known as sustentacular cells. The olfactory neurons project their axons to the olfactory bulb in the central nervous system offering a potential pathway for pathogens to enter the central nervous system by bypassing the blood brain barrier. In the present study, we explored the impact of SARS-COV-2 infection on the olfactory system in golden Syrian hamsters. We observed massive damage of the OE as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection. These damages were associated with infection of a large proportion of sustentacular cells but not of olfactory neurons, and we did not detect any presence of the virus in the olfactory bulbs. We observed massive infiltration of immune cells in the OE and lamina propria of infected animals, which may contribute to the desquamation of the OE. The OE was partially restored 14 days post infection. Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria.

scholarly journals Novel Therapeutics for Epstein–Barr Virus

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 997 ◽  
Author(s):  
Graciela Andrei ◽  
Erika Trompet ◽  
Robert Snoeck
Keyword(s):  
B Cells ◽  
Epithelial Cells ◽  
Epstein Barr Virus ◽  
Adult Population ◽  
Antiviral Drug ◽  
Barr Virus ◽  
Epstein Barr ◽  
New Strategies

Epstein–Barr virus (EBV) is a human γ-herpesvirus that infects up to 95% of the adult population. Primary EBV infection usually occurs during childhood and is generally asymptomatic, though the virus can cause infectious mononucleosis in 35–50% of the cases when infection occurs later in life. EBV infects mainly B-cells and epithelial cells, establishing latency in resting memory B-cells and possibly also in epithelial cells. EBV is recognized as an oncogenic virus but in immunocompetent hosts, EBV reactivation is controlled by the immune response preventing transformation in vivo. Under immunosuppression, regardless of the cause, the immune system can lose control of EBV replication, which may result in the appearance of neoplasms. The primary malignancies related to EBV are B-cell lymphomas and nasopharyngeal carcinoma, which reflects the primary cell targets of viral infection in vivo. Although a number of antivirals were proven to inhibit EBV replication in vitro, they had limited success in the clinic and to date no antiviral drug has been approved for the treatment of EBV infections. We review here the antiviral drugs that have been evaluated in the clinic to treat EBV infections and discuss novel molecules with anti-EBV activity under investigation as well as new strategies to treat EBV-related diseases.

scholarly journals Infection of Hysterectomized Mice with Chlamydia muridarum and Chlamydia trachomatis

2017 ◽  
Vol 85 (7) ◽  
Author(s):  
Chunfu Yang ◽  
William M. Whitmire ◽  
Gail L. Sturdevant ◽  
Kevin Bock ◽  
Ian Moore ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Genital Tract ◽  
Plasma Cells ◽  
T Cell Response ◽  
Similar Species ◽  
Content Type ◽  
Chlamydia Muridarum

ABSTRACT We studied infection and immunity of hysterectomized mice infected with Chlamydia muridarum and Chlamydia trachomatis to determine if there were differences between these species in their ability to infect vaginal squamous epithelial cells in vivo independently of proximal upper genital tract tissues. We found that C. muridarum readily colonized and infected vaginal squamous epithelial cells, whereas C. trachomatis did not. Primary infection of the vaginal epithelium with C. muridarum produced infections of a duration longer than that reported for normal mice. Infection resulted in an inflammatory response in the vagina characterized by neutrophils and infiltrating submucosal plasma cells consisting primarily of T cells. Despite the delayed clearance, rechallenged C. muridarum-infected mice were highly immune. Mice vaginally infected with C. muridarum produced serum and vaginal wash antibodies and an antigen-specific gamma interferon-dominated Th1-biased T cell response. By comparison, mice vaginally infected with C. trachomatis exhibited transient low-burden infections, produced no detectable tissue inflammatory response, and failed to seroconvert. We discuss how these marked differences in the biology of vaginal infection between these otherwise genetically similar species are possibly linked to pathogen-specific virulence genes and how they may influence pathology and immunity in the upper genital tract.

scholarly journals Differential Expression of the miR-200 Family MicroRNAs in Epithelial and B Cells and Regulation of Epstein-Barr Virus Reactivation by the miR-200 Family Member miR-429

2010 ◽  
Vol 84 (15) ◽  
pp. 7892-7897 ◽  
Author(s):  
Zhen Lin ◽  
Xia Wang ◽  
Claire Fewell ◽  
Jennifer Cameron ◽  
Qinyan Yin ◽  
...  
Keyword(s):  
B Cells ◽  
Epithelial Cells ◽  
Family Member ◽  
Epstein Barr Virus ◽  
Family Members ◽  
Receptor Activation ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Epstein Barr

ABSTRACT The miR-200 microRNA family is important for maintaining the epithelial phenotype, partially through suppressing ZEB1 and ZEB2. Since ZEB1 inhibits Epstein-Barr virus (EBV) reactivation, we hypothesized that expression of miR-200 family members in epithelial cells may partly account for higher levels of EBV reactivation in this tissue (relative to nonplasma B cells). Here we show that, whereas miR-200 family members are expressed in epithelial cells, their expression is low in latently infected B cells. Furthermore, the miR-200 family member miR-429 shows elevated expression in plasma cell lines and is induced by B-cell-receptor activation in Akata cells. Lastly, expression of miR-429 can break latency.

scholarly journals Resolution of Secondary Chlamydia trachomatis Genital Tract Infection in Immune Mice with Depletion of Both CD4+ and CD8+ T cells

2001 ◽  
Vol 69 (4) ◽  
pp. 2643-2649 ◽  
Author(s):  
Sandra G. Morrison ◽  
Richard P. Morrison
Keyword(s):  
T Cells ◽  
B Cells ◽  
Chlamydia Trachomatis ◽  
Tract Infection ◽  
Genital Tract ◽  
Delayed Type Hypersensitivity ◽  
Predominant Role ◽  
Genital Tract Infection

ABSTRACT The essential role of T cells in the resolution of primary murineChlamydia trachomatis genital tract infection is inarguable; however, much less is known about the mechanisms that confer resistance to reinfection. We previously established that CD4+ T cells and B cells contribute importantly to resistance to reinfection. In our current studies, we demonstrate that immune mice concurrently depleted of both CD4+ T cells and CD8+ T cells resisted reinfection as well as immunocompetent wild-type mice. The in vivo depletion of CD4+ and CD8+ T cells resulted in diminished chlamydia-specific delayed-type hypersensitivity responses, but antichlamydial antibody responses were unaffected. Our data indicate that immunity to chlamydial genital tract reinfection does not rely solely upon immune CD4+ or CD8+ T cells and further substantiate a predominant role for additional effector immune responses, such as B cells, in resistance to chlamydial genital tract reinfection.

scholarly journals Immunization of the Female Genital Tract with a DNA-Based Vaccine

1998 ◽  
Vol 66 (1) ◽  
pp. 322-329 ◽  
Author(s):  
Julie B. Livingston ◽  
Shan Lu ◽  
Harriet Robinson ◽  
Deborah J. Anderson
Keyword(s):  
Genital Tract ◽  
Female Genital Tract ◽  
Female Rats ◽  
Vaginal Mucosa ◽  
Gene Gun ◽  
Local Immunity ◽  
Vaginal Secretions ◽  
Antibody Titers ◽  
Female Genital

ABSTRACT Vaccines are being sought for contraception and the prevention of sexually transmitted diseases. However, progress is slow in this area largely because of lack of information on induction of protective immune responses in genital tract mucosa. In this study, we investigated whether in vivo transfection with a model DNA-based antigen delivered by gene gun technology would induce an antibody response detectable in vaginal secretions. Female rats were immunized with plasmids encoding human growth hormone (HGH) under the control of a cytomegalovirus promoter (pCMV/HGH) via vaginal mucosa (V), Peyer’s patch (PP), and/or abdominal skin (S) routes. Localization of HGH in the target tissues demonstrated that all three sites can be transfected in vivo with pCMV/HGH. Vaginal tissues expressed roughly the same level of plasmid as skin. Antibodies to HGH were detectable in serum and vaginal secretions in rats immunized with pCMV/HGH. In the rats primed and boosted vaginally, vaginal immunoglobulin A (IgA) and IgG antibody titers to HGH were sustained for at least 14 weeks, whereas rats immunized via other routes and protocols (S/V, S/S, PP/PP, or PP/V) did not consistently sustain significant vaginal antibody titers beyond week 6. DNA-based immunizations administered by the gene gun may be an effective method of inducing local immunity in the female genital tract.

In vivo modulation of gap junctions and dye coupling between B-cells of the intact pancreatic islet

Diabetes ◽  
1983 ◽  
Vol 32 (9) ◽  
pp. 858-868 ◽  
Author(s):  
P. Meda ◽  
R. L. Michaels ◽  
P. A. Halban ◽  
L. Orci ◽  
J. D. Sheridan
Keyword(s):  
B Cells ◽  
Gap Junctions ◽  
Pancreatic Islet ◽  
Dye Coupling
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