scholarly journals Equine Herpesvirus-1 Interferes with Type-I IFN-Mediated Immune Responses in vitro in Equine Endothelial Cells

2016 ◽  
Vol 39 ◽  
pp. S67
Author(s):  
S. Sarkar ◽  
U.B.R. Balasuriya ◽  
D.W. Horohov ◽  
T.M. Chambers
Keyword(s):  
Endothelial Cells ◽  
Immune Responses ◽  
Type I ◽  
Equine Herpesvirus ◽  
Type I Ifn ◽  
Equine Herpesvirus 1 ◽  
Herpesvirus 1

scholarly journals Equid Herpesvirus 1 Targets the Sensitization and Induction Steps To Inhibit the Type I Interferon Response in Equine Endothelial Cells

2019 ◽  
Vol 93 (23) ◽  
Author(s):  
Fatai S. Oladunni ◽  
Sanjay Sarkar ◽  
Stephanie Reedy ◽  
Udeni B. R. Balasuriya ◽  
David W. Horohov ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cellular Level ◽  
Immune Defense ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn ◽  
Viral Pathogen ◽  
Equid Herpesvirus ◽  
Herpesvirus 1

ABSTRACT Equid herpesvirus 1 (EHV-1) is a viral pathogen of horse populations worldwide spread by the respiratory route and is known for causing outbreaks of neurologic syndromes and abortion storms. Previously, we demonstrated that an EHV-1 strain of the neuropathogenic genotype, T953, downregulates the beta interferon (IFN-β) response in vitro in equine endothelial cells (EECs) at 12 h postinfection (hpi). In the present study, we explored the molecular correlates of this inhibition as clues toward an understanding of the mechanism. Data from our study revealed that EHV-1 infection of EECs significantly reduced both Toll-like receptor 3 (TLR3) and TLR4 mRNA expression at 6 hpi and 12 hpi. While EHV-1 was able to significantly reduce IRF9 mRNA at both 6 hpi and 12 hpi, the virus significantly reduced IFN regulatory factor 7 (IRF7) mRNA only at 12 hpi. EHV-1 did not alter the cellular level of Janus-activated kinase 1 (JAK1) at any time point. However, EHV-1 reduced the cellular level of expression of tyrosine kinase 2 (TYK2) at 12 hpi. Downstream of JAK1-TYK2 signaling, EHV-1 blocked the phosphorylation and activation of signal transducer and activator of transcription 2 (STAT2) when coincubated with exogenous IFN, at 12 hpi, although not at 3 or 6 hpi. Immunofluorescence staining revealed that the virus prevented the nuclear translocation of STAT2 molecules, confirming the virus-mediated inhibition of STAT2 activation. The pattern of suppression of phosphorylation of STAT2 by EHV-1 implicated viral late gene expression. These data help illuminate how EHV-1 strategically inhibits the host innate immune defense by limiting steps required for type I IFN sensitization and induction. IMPORTANCE To date, no commercial vaccine label has a claim to be fully protective against the diseases caused by equid herpesvirus 1 (EHV-1), especially the neurologic form. The interferon (IFN) system, of which type I IFN is of great importance, still remains a viable immunotherapeutic option against EHV-1 infection. The type I IFN system has been exploited successfully to treat other viral infections, such as chronic hepatitis B and C in humans. The current state of research on how EHV-1 interferes with the protective effect of type I IFN has indicated transient induction of type I IFN production followed by a rapid shutdown in vitro in equine endothelial cells (EECs). The significance of our study is the identification of certain steps in the type I IFN signaling pathway targeted for inhibition by EHV-1. Understanding this pathogen-host relationship is essential for the long-term goal of developing effective immunotherapy against EHV-1.

Modulation of type-I IFN response by equine herpesvirus-1

2012 ◽  
Vol 32 (10) ◽  
pp. S28-S29
Author(s):  
S. Sarkar ◽  
U.B.R. Balasuriya ◽  
D.W. Horohov ◽  
T.M. Chambers
Keyword(s):  
Type I ◽  
Equine Herpesvirus ◽  
Type I Ifn ◽  
Equine Herpesvirus 1 ◽  
Herpesvirus 1

Equine herpesvirus-1 suppresses type-I interferon induction in equine endothelial cells

2015 ◽  
Vol 167 (3-4) ◽  
pp. 122-129 ◽  
Author(s):  
Sanjay Sarkar ◽  
Udeni B.R. Balasuriya ◽  
David W. Horohov ◽  
Thomas M. Chambers
Keyword(s):  
Endothelial Cells ◽  
Type I Interferon ◽  
Type I ◽  
Equine Herpesvirus ◽  
Equine Herpesvirus 1 ◽  
Interferon Induction ◽  
Herpesvirus 1

scholarly journals Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice

2017 ◽  
Vol 91 (12) ◽  
Author(s):  
Shiliang A. Liu ◽  
Brent A. Stanfield ◽  
Vladimir N. Chouljenko ◽  
Shan Naidu ◽  
Ingeborg Langohr ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Strain ◽  
Equine Herpesvirus ◽  
Herpes Simplex Virus 1 ◽  
Equine Herpesvirus 1 ◽  
Cellular Immune Responses ◽  
Herpesvirus 1 ◽  
Simplex Virus ◽  
Cellular Immune ◽  
Hsv 1

ABSTRACT Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the live-attenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses. The VC2–EHV-1–gD recombinant virus was constructed by inserting an EHV-1 gD expression cassette under the control of the cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV-1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through intramuscular injection. Vaccination with both the VC2–EHV-1–gD vaccine and the commercially available vaccine Vetera EHVXP 1/4 (Vetera; Boehringer Ingelheim Vetmedica) resulted in the production of neutralizing antibodies, the levels of which were significantly higher in comparison to those in VC2- and mock-vaccinated animals (P < 0.01 or P < 0.001). Analysis of EHV-1-reactive IgG subtypes demonstrated that vaccination with the VC2–EHV-1–gD vaccine stimulated robust IgG1 and IgG2a antibodies after three vaccinations (P < 0.001). Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM than mice in the other groups before and after challenge (P < 0.01 or P < 0.05). Vaccination with VC2–EHV-1–gD stimulated strong cellular immune responses, characterized by the upregulation of both interferon- and tumor necrosis factor-positive CD4+ T cells and CD8+ T cells. Overall, the data suggest that the HSV-1 VC2 vaccine strain may be used as a viral vector for the vaccination of horses as well as, potentially, for the vaccination of other economically important animals. IMPORTANCE A novel virus-vectored VC2–EHV-1–gD vaccine was constructed using the live-attenuated HSV-1 VC2 vaccine strain. This vaccine stimulated strong humoral and cellular immune responses in mice, suggesting that it could protect horses against EHV-1 infection.

scholarly journals In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

2007 ◽  
Vol 122 (1-2) ◽  
pp. 43-51 ◽  
Author(s):  
B GARRE ◽  
K VANDERMEULEN ◽  
J NUGENT ◽  
J NEYTS ◽  
S CROUBELS ◽  
...  
Keyword(s):  
Equine Herpesvirus ◽  
In Vitro Susceptibility ◽  
Equine Herpesvirus 1 ◽  
Herpesvirus 1

scholarly journals Peptide transport activity of the transporter associated with antigen processing (TAP) is inhibited by an early protein of equine herpesvirus-1

2004 ◽  
Vol 85 (2) ◽  
pp. 349-353 ◽  
Author(s):  
Aruna P. N. Ambagala ◽  
Raju S. Gopinath ◽  
S. Srikumaran
Keyword(s):  
Antigen Processing ◽  
Protein S ◽  
Class I ◽  
Peptide Transport ◽  
Equine Herpesvirus ◽  
Equine Herpesvirus 1 ◽  
Early Protein ◽  
Infected Cells ◽  
Herpesvirus 1

Equine herpesvirus-1 (EHV-1) downregulates surface expression of major histocompatibility complex (MHC) class I molecules on infected cells. The objective of this study was to investigate whether EHV-1 interferes with peptide translocation by the transporter associated with antigen processing (TAP) and to identify the proteins responsible. Using an in vitro transport assay, we showed that EHV-1 inhibited transport of peptides by TAP as early as 2 h post-infection (p.i). Complete shutdown of peptide transport was observed by 8 h p.i. Furthermore, pulse–chase experiments revealed that maturation of class I molecules in the endoplasmic reticulum (ER) was delayed in EHV-1-infected cells, which may be due to reduced availability of peptides in the ER as a result of TAP inhibition. Metabolic inhibition studies indicated that an early protein(s) of EHV-1 is responsible for this effect.

scholarly journals Immunization with Attenuated Equine Herpesvirus 1 Strain KyA Induces Innate Immune Responses That Protect Mice from Lethal Challenge

2016 ◽  
Vol 90 (18) ◽  
pp. 8090-8104 ◽  
Author(s):  
Seong K. Kim ◽  
Akhalesh K. Shakya ◽  
Dennis J. O'Callaghan
Keyword(s):  
Immune Responses ◽  
Alveolar Macrophages ◽  
Innate Immune ◽  
Equine Herpesvirus ◽  
Innate Immune Responses ◽  
Lethal Challenge ◽  
Equine Herpesvirus 1 ◽  
Interferon Stimulated Genes ◽  
Ifn Γ ◽  
Herpesvirus 1

ABSTRACTEquine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide. The virus causes respiratory disease, abortion, and, in some cases, neurological disease. EHV-1 strain KyA is attenuated in the mouse and equine, whereas wild-type strain RacL11 induces severe inflammation of the lung, causing infected mice to succumb at 4 to 6 days postinfection. Our previous results showed that KyA immunization protected CBA mice from pathogenic RacL11 challenge at 2 and 4 weeks postimmunization and that KyA infection elicited protective humoral and cell-mediated immune responses. To investigate the protective mechanisms of innate immune responses to KyA, KyA-immunized mice were challenged with RacL11 at various times postvaccination. KyA immunization protected mice from RacL11 challenge at 1 to 7 days postimmunization. Immunized mice lost less than 10% of their body weight and rapidly regained weight. Virus titers in the lungs of KyA-immunized mice were 1,000-fold lower at 2 days post-RacL11 challenge than virus titers in the lungs of nonimmunized mice, indicating accelerated virus clearance. Affymetrix microarray analysis revealed that gamma interferon (IFN-γ) and 16 antiviral interferon-stimulated genes (ISGs) were upregulated 3.1- to 48.2-fold at 8 h postchallenge in the lungs of RacL11-challenged mice that had been immunized with KyA. Murine IFN-γ inhibited EHV-1 infection of murine alveolar macrophages and protected mice against lethal EHV-1 challenge, suggesting that IFN-γ expression is important in mediating the protection elicited by KyA immunization. These results suggest that EHV-1 KyA may be used as a live attenuated EHV-1 vaccine as well as a prophylactic agent in horses.IMPORTANCEViral infection of cells initiates a signal cascade of events that ultimately attempts to limit viral replication and prevent infection through the expression of host antiviral proteins. In this study, we show that EHV-1 KyA immunization effectively protected CBA mice from pathogenic RacL11 challenge at 1 to 7 days postvaccination and increased the expression of IFN-γ and 16 antiviral interferon-stimulated genes (ISGs). The administration of IFN-γ blocked EHV-1 replication in murine alveolar macrophages and mouse lungs and protected mice from lethal challenge. To our knowledge, this is the first report of an attenuated EHV-1 vaccine that protects the animal at 1 to 7 days postimmunization by innate immune responses. Our findings suggested that IFN-γ serves as a novel prophylactic agent and may offer new strategies for the development of anti-EHV-1 agents in the equine.

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