Innate immune responses of airway epithelial cells to infection with Equine herpesvirus-1

Hussey, Gisela Soboll; Ashton, Laura V.; Quintana, Ayshea M.; Lunn, D.P.; Goehring, Lutz S.; Annis, Kristina M.; Landolt, Gabriele A.

doi:10.1016/j.vetmic.2014.01.018

Cited by 27 publications

(29 citation statements)

References 41 publications

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“…Moreover, EHV-1 seemed to induce different cytokine responses regarding the cell type infected. The strain Ab4 induced an increased mRNA expression of IFN-α, IFN-β, and TNF-α after infection of equine respiratory epithelial cells (EREC) [ 16 ]. IL-1β, IL-6, IL-8, and IL-12 mRNA expression were also increased in Ab4 infected EREC [ 16 , 32 ], whereas no modulation was described after PBMC infection [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…In this condition, the host ability to fight these pathogens is essential. At the present time, very few data are available on the immune response induced by EHV-1, EHV-4, and EHV-2 infection [ 15 , 16 , 17 ]. Generally, the secretion of type I interferon (IFN) was associated with the duration of virus shedding and could be a result of viral replication.…”

Section: Introductionmentioning

confidence: 99%

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Equine PBMC Cytokines Profile after In Vitro α- and γ-EHV Infection: Efficacy of a Parapoxvirus Ovis Based-Immunomodulator Treatment

et al. 2017

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Equine herpesviruses (EHV) infect horses early during life and the persistence of these viruses through establishment of latency represents a real risk. A better understanding of the immune response to EHV infection is necessary to improve our methods of prevention and decrease the risk of transmission. The objectives of this study were to characterise the cytokine gene expression profile of peripheral blood mononuclear cells (PBMC) after in vitro EHV-1, EHV-4, and EHV-2 infection and to determine the efficacy of inactivated Parapoxvirus ovis (iPPVO) against these 3 viruses. PBMC were isolated from 3 horses and infected in vitro with EHV-1, EHV-4, or EHV-2 in the presence or absence of iPPVO. In vitro culture of PBMC with EHV-1, EHV-4, and iPPVO induced a significant increase of IFN-α, IFN-β, and IFN-γ gene expression. EHV-4 also triggered a significant increase of IL-6 and TNF-α mRNA. EHV-2 triggered a significant increase of IFN-α, IFN-β, IFN-γ, IL-1β, IL-6, and TNF-α mRNA. The presence of iPPVO induced an earlier and stronger expression of IFN-α, IFN-β, and IFN-γ mRNA during EHV infection and reduced the inflammatory response induced by EHV-2. In conclusion, this study suggests that the presence of iPPVO potentiates the development of the immune response to in vitro EHV infection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Equine PBMC Cytokines Profile after In Vitro α- and γ-EHV Infection: Efficacy of a Parapoxvirus Ovis Based-Immunomodulator Treatment

et al. 2017

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“…In this regard, comparison of alphaherpesvirus genomes showed that varicellazoster virus, pseudorabies virus, and HSV-1 are similar in structure to EHV-1 and that each of these viruses encodes a protein that shares extensive homology with the EHV-1 immediate early protein (65,66). Infection with EHV-1 wild-type strain Ab4 reduced IFN-␥ production in primary equine respiratory epithelial cells (67). Our microarray data showed that infection with EHV-1 KyA or RacL11 was not able to induce IFN-␥ gene expression (Ͻ2-fold increase) in the lungs of CBA mice at 8 h postinfection.…”

Section: Discussionmentioning

confidence: 99%

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

Kim

Shakya

O’Callaghan

2016

J Virol

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Equine 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 Equine herpesvirus 1 (EHV-1), a member of the family Herpesviridae and the subfamily Alphaherpesvirinae, is the causative agent of a number of equine pathological states, including severe disease of the central nervous system, respiratory infections, and abortion storms (1-4). Respiratory transmission of this highly contagious virus has resulted in disastrous outbreaks of disease in domestic horse populations and has had significant economic impact on the equine industry. EHV-1 infection of the horse generates a short-lived humoral response but does not confer long-term protection, since disease often occurs following natural infection (5, 6).A model that closely mimics EHV-1 infection in the natural host has been established with various strains of mice (7). Common features include replication in the respiratory mucosae, the development of pneumonitis, cell-associated viremia, and abortion (7,8). Various EHV-1 glycoproteins, including gB, gC, gD, and gH, were capable of inducing neutralizing antibodies (9-14). EHV-1-specific CD8 ϩ class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) were identified in the peripheral blood mononuclear cells of infected horses, reaching maximal levels 2 to 3 weeks postinfection (15,16). Intranasal inoculation of mice with an attenuated EHV-1 strain, KyA, resulted in the production of a primary virus-specific CTL response in the draining mediastinal lymph nodes (17). In this model, EHV-1-specific CTL activity was mediated by class I MHC-restricted CD8 ϩ T cells (17). The nonpathogenic EHV-1 strain Kentucky A (KyA) is attenuated in mice and horses, whereas the wild-type pathogenic strain RacL11 induces severe inflammatory cell infiltration in the lung, such that infected mice succumb at 4 to 6 days postinfection (dpi) (Fig. 1) (18-23). RacL11 was isolated from an aborted fetus (24). KyA has a long history of passage outside the natural host and

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“…Sarkar et al ( 2015 ) demonstrated that the neurovirulent T953 strain shuts down IFNβ production in equine endothelial cells upon the expression of late viral proteins. Primary respiratory epithelial cells inoculated with the neurotropic Ab4 strain showed an up-regulation of mRNA expression of IFNα, which indicates the activation of the IFN response in the URT (Soboll Hussey et al, 2014 ). Intriguingly, recent studies of the URT demonstrated that chemokine expression varied between abortigenic and neurovirulent EHV1 strains in vivo and ex vivo (Holz et al, 2017 ; Zhao et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Abortigenic but Not Neurotropic Equine Herpes Virus 1 Modulates the Interferon Antiviral Defense

Poelaert

Cleemput

Laval

et al. 2018

Front. Cell. Infect. Microbiol.

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Equine herpesvirus 1 (EHV1) is considered as a major pathogen of Equidae, causing symptoms from mild respiratory disease to late-term abortion and neurological disorders. Different EHV1 strains circulating in the field have been characterized to be of abortigenic or neurovirulent phenotype. Both variants replicate in a plaque-wise manner in the epithelium of the upper respiratory tract (URT), where the abortigenic strains induce more prominent viral plaques, compared to the neurovirulent strains. Considering the differences in replication at the URT, we hypothesized that abortigenic strains may show an increased ability to modulate the type I IFN secretion/signaling pathway, compared to strains that display the neurovirulent phenotype. Here, we analyze IFN levels induced by abortigenic and neurovirulent EHV1 using primary respiratory epithelial cells (EREC) and respiratory mucosa ex vivo explants. Similar levels of IFNα (~70 U/ml) were detected in explants inoculated with both types of EHV1 strains from 48 to 72 hpi. Second, EREC and mucosa explants were treated with recombinant equine IFNα (rEqIFNα) or Ruxolitinib (Rux), an IFN signaling inhibitor, prior to and during inoculation with abortigenic or neurovirulent EHV1. Replication of both EHV1 variants was suppressed by rEqIFNα. Further, addition of Rux increased replication in a concentration-dependent manner, indicating an IFN-susceptibility for both variants. However, in two out of three horses, at a physiological concentration of 100 U/ml of rEqIFNα, an increase in abortigenic EHV1 replication was observed compared to 10 U/ml of rEqIFNα, which was not observed for the neurovirulent strains. Moreover, in the presence of Rux, the plaque size of the abortigenic variants remained unaltered, whereas the typically smaller viral plaques induced by the neurovirulent variants became larger. Overall, our results demonstrate the importance of IFNα in the control of EHV1 replication in the URT for both abortigenic and neurovirulent variants. In addition, our findings support the speculation that abortigenic variants of EHV1 may have developed anti-IFN mechanisms that appear to be absent or less pronounced in neurovirulent EHV1 strains.

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Innate immune responses of airway epithelial cells to infection with Equine herpesvirus-1

Cited by 27 publications

References 41 publications

Equine PBMC Cytokines Profile after In Vitro α- and γ-EHV Infection: Efficacy of a Parapoxvirus Ovis Based-Immunomodulator Treatment

Equine PBMC Cytokines Profile after In Vitro α- and γ-EHV Infection: Efficacy of a Parapoxvirus Ovis Based-Immunomodulator Treatment

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

Abortigenic but Not Neurotropic Equine Herpes Virus 1 Modulates the Interferon Antiviral Defense

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