scholarly journals Exogenous Expression of Equine MHC Class I Molecules in Mice Increases Susceptibility to Equine Herpesvirus 1 Pulmonary Infection

2019 ◽  
Vol 56 (5) ◽  
pp. 703-710 ◽  
Author(s):  
Erina Minato ◽  
Keisuke Aoshima ◽  
Atsushi Kobayashi ◽  
Naomi Ohnishi ◽  
Nobuya Sasaki ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Virus Antigen ◽  
Class I ◽  
Equine Herpesvirus ◽  
Class I Mhc ◽  
Equine Herpesvirus 1 ◽  
Exogenous Expression ◽  
Herpesvirus 1 ◽  
Entry Receptor

Equine herpesvirus 1 (EHV-1) uses equine major histocompatibility complex class I (MHC class I) as an entry receptor. Exogenous expression of equine MHC class I genes in murine cell lines confers susceptibility to EHV-1 infection. To examine the in vivo role of equine MHC class I as an entry receptor for EHV-1, we generated transgenic (Tg) mice expressing equine MHC class I under the control of the CAG promoter. Equine MHC class I protein was expressed in the liver, spleen, lung, and brain of Tg mice, which was confirmed by Western blot. However, equine MHC class I antigen was only detected in bronchiolar epithelium and not in other tissues, using the immunofluorescence method employed in this study. Both Tg and wild-type (WT) mice developed pneumonia 3 days after intranasal infection with EHV-1. The bronchiolar epithelial cells of Tg mice showed more severe necrosis, compared with those in WT mice. In addition, the number of virus antigen-positive cells in the lungs was higher in Tg mice than in WT mice. These results suggest that exogenous expression of equine MHC class I renders mice more susceptible to EHV-1 infection.

scholarly journals A molecular approach to the identification of cytotoxic T-lymphocyte epitopes within equine herpesvirus 1

2006 ◽  
Vol 87 (9) ◽  
pp. 2507-2515 ◽  
Author(s):  
Julia H. Kydd ◽  
N. J. Davis-Poynter ◽  
J. Birch ◽  
D. Hannant ◽  
J. Minke ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Target Cells ◽  
Equine Herpesvirus ◽  
Equine Herpesvirus 1 ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
Herpesvirus 1 ◽  
Functional Peptide

Equine herpesvirus 1 (EHV-1) causes respiratory and neurological disease and abortion in horses. Animals with high frequencies of cytotoxic T lymphocytes (CTL) show reduced severity of respiratory disease and frequency of abortion, probably by CTL-mediated control of cell-associated viraemia. This study aimed to identify CTL epitopes restricted by selected major histocompatibility complex (MHC) class I alleles expressed in the equine leukocyte antigen (ELA) A3 haplotype. Effector CTL were induced from EHV-1-primed ponies and thoroughbreds with characterized MHC class I haplotypes and screened against P815 target cells transfected with selected EHV-1 genes and MHC class I genes. Targets that expressed EHV-1 gene 64 and the MHC B2 gene were lysed by effector CTL in a genetically restricted manner. There was no T-cell recognition of targets expressing either the MHC B2 gene and EHV-1 genes 2, 12, 14, 16, 35, 63 or 69, or the MHC C1 gene and EHV-1 genes 12, 14, 16 or 64. A vaccinia virus vector encoding gene 64 (NYVAC-64) was also investigated. Using lymphocytes from ELA-A3 horses, the recombinant NYVAC-64 virus induced effector CTL that lysed EHV-1-infected target cells; the recombinant virus also supplied a functional peptide that was expressed by target cells and recognized in an MHC-restricted fashion by CTL induced with EHV-1. This construct may therefore be used to determine the antigenicity of EHV-1 gene 64 for other MHC haplotypes. These techniques are broadly applicable to the identification of additional CTL target proteins and their presenting MHC alleles, not only for EHV-1, but for other equine viruses.

scholarly journals Down-regulation of MHC class I expression by equine herpesvirus-1

2003 ◽  
Vol 84 (2) ◽  
pp. 293-300 ◽  
Author(s):  
Giovanna Rappocciolo ◽  
James Birch ◽  
Shirley A. Ellis
Keyword(s):  
Mhc Class I ◽  
Class I ◽  
Equine Herpesvirus ◽  
Down Regulation ◽  
Equine Herpesvirus 1 ◽  
Herpesvirus 1

scholarly journals Immunotherapy of a murine tumor with interleukin 2. Increased sensitivity after MHC class I gene transfection.

1987 ◽  
Vol 166 (6) ◽  
pp. 1716-1733 ◽  
Author(s):  
J S Weber ◽  
G Jay ◽  
K Tanaka ◽  
S A Rosenberg
Keyword(s):  
T Cells ◽  
Mhc Class I ◽  
Interleukin 2 ◽  
Class I ◽  
High Dose ◽  
Class I Mhc ◽  
High Doses ◽  
I Gene

We have shown that two weakly immunogenic MCA sarcomas developed in our laboratory that are sensitive to high-dose IL-2 immunotherapy express class I MHC in vivo and in vitro. Two nonimmunogenic MCA sarcomas are relatively insensitive to IL-2 therapy and express minimal or no class I MHC molecules in vivo and in vitro. To study the role of MHC in the therapy of tumors with IL-2, a class I-deficient murine melanoma, B16BL6, was transfected with the Kb class I gene. Expression of class I MHC rendered B16BL6 advanced pulmonary macrometastases sensitive to IL-2 immunotherapy. 3-d micrometastases of CL8-2, a class I transfected clone of B16BL6, were significantly more sensitive to IL-2 therapy than a control nontransfected line. Expression of Iak, a class II MHC molecule, had no effect on IL-2 therapy of transfectant pulmonary micrometastases in F1 mice. By using lymphocyte subset depletion with mAbs directed against Lyt-2, therapy of class I transfectant macrometastases with high-dose IL-2 was shown to involve an Lyt-2 cell. In contrast, regression of micrometastases treated with low-dose IL-2 involved Lyt-2+ cells, but regression mediated by high doses of IL-2 did not. We hypothesize that both LAK and Lyt-2+ T cells effect IL-2-mediated elimination of micrometastases, but only Lyt-2+ T cells are involved in macrometastatic regression. Low doses of IL-2 stimulate Lyt-2+ cells to eliminate class I-expressing micrometastases, but high doses of IL-2 can recruit LAK cells to mediate regression of micrometastases independent of class I expression. Only high-dose IL-2, mediating its effect predominantly via Lyt-2+ cells, is capable of impacting on MHC class I-expressing macrometastases. Macrometastases devoid of class I MHC antigens appear to be resistant to IL-2 therapy.

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.

Engraftment of C6-2B Cells into the Striatum of Aci Nude Rats as a Tool for Comparison of the in Vitro and in Vivo Phenotype of a Glioma Cell Line

1997 ◽  
Vol 6 (3) ◽  
pp. 317-326 ◽  
Author(s):  
Carlo Tornatore ◽  
Stuart Rabin ◽  
Belinda Baker-Cairns ◽  
Stuart Keir ◽  
Italo Mocchetti
Keyword(s):  
Inflammatory Response ◽  
Cell Line ◽  
Mhc Class I ◽  
Glioma Cell ◽  
Glioma Cell Line ◽  
Class I ◽  
Class I Mhc ◽  
Nude Rats

The C6-2B is a well-characterized glioma cell line used extensively in the study of malignant glial biology. While the C6-2B cell line has traditionally been thought of as a homogenous cell line, the in vitro phenotype of the C6-2B cell line can vary considerably depending on the culture technique used and the stratum on which the cells are grown. Thus, we asked whether the in vitro phenotype of the C6-2B cell line was significantly different than the in vivo phenotype of the cell line once it was engrafted into the striatum of nude rats. Under culture conditions used in our laboratory, 100% of the C6 cells were found to express p75, the low-affinity nerve growth factor (NGF) receptor, and Major Histocompatability Class I (MHC Class I), while only 10-15% demonstrated vimentin reactivity. Immunohistochemistry was consistently negative for GFAP, trkA (the high-affinity receptor for NGF), CD4, CD8, and a macrophage specific marker (Ox-41). Once engrafted into the striatum of nude rats, the cells remained 100% p75 and MHC Class I positive, and again, only 15% of the cells demonstrated vimentin reactivity. The grafted cells retained this characteristic for 28 days in vivo. Although an immunoincompetent host was selected to minimize the effects an inflammatory response would have on the graft, a transient inflammatory response was detected. During the first week of engraftment, numerous MHC class II cells, some of which were macrophages, were seen infiltrating the graft. However, by 4 weeks postengraftment, no inflammatory cells were appreciated in the graft and surprisingly little reactive gliosis was seen in the penumbra of the tumor mass. Thus, the limited number of in vitro phe-notypic characteristics we examined in the C6-2B cell line remained constant once the cells were engrafted into the striatum of athymic nude rats.

scholarly journals Immunoreceptor tyrosine-based inhibitory motif–dependent functions of an MHC class I-specific NK cell receptor

2017 ◽  
Vol 114 (40) ◽  
pp. E8440-E8447 ◽  
Author(s):  
Michael D. Bern ◽  
Diana L. Beckman ◽  
Takashi Ebihara ◽  
Samantha M. Taffner ◽  
Jennifer Poursine-Laurent ◽  
...  
Keyword(s):  
Nk Cells ◽  
Mhc Class I ◽  
Nk Cell ◽  
Single Gene ◽  
Cell Receptor ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Receptor Repertoire

Natural killer (NK) cells express MHC class I (MHC-I)-specific receptors, such as Ly49A, that inhibit killing of cells expressing self–MHC-I. Self–MHC-I also “licenses” NK cells to become responsive to activating stimuli and regulates the surface level of NK-cell inhibitory receptors. However, the mechanisms of action resulting from these interactions of the Ly49s with their MHC-I ligands, particularly in vivo, have been controversial. Definitive studies could be derived from mice with targeted mutations in inhibitory Ly49s, but there are inherent challenges in specifically altering a single gene within a multigene family. Herein, we generated a knock-in mouse with a targeted mutation in the immunoreceptor tyrosine-based inhibitory motif (ITIM) of Ly49A that abolished the inhibitory function of Ly49A in cytotoxicity assays. This mutant Ly49A caused a licensing defect in NK cells, but the surface expression of Ly49A was unaltered. Moreover, NK cells that expressed this mutant Ly49A exhibited an altered inhibitory receptor repertoire. These results demonstrate that Ly49A ITIM signaling is critical for NK-cell effector inhibition, licensing, and receptor repertoire development.

scholarly journals A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1

2021 ◽  
Vol 8 ◽  
Author(s):  
Lila M. Zarski ◽  
Wendy E. Vaala ◽  
D. Craig Barnett ◽  
Fairfield T. Bain ◽  
Gisela Soboll Hussey
Keyword(s):  
Innate Immunity ◽  
Influenza Vaccine ◽  
Equine Herpesvirus ◽  
Equine Herpesvirus 1 ◽  
Equine Influenza ◽  
Antiviral Responses ◽  
Herpesvirus 1 ◽  
Antiviral Innate Immunity ◽  
Respiratory Epithelial

Equine herpesvirus 1 (EHV-1) ubiquitously infects horses worldwide and causes respiratory disease, abortion, and equine herpesvirus myeloencephalopathy. Protection against EHV-1 disease is elusive due to establishment of latency and immune-modulatory features of the virus. These include the modulation of interferons, cytokines, chemokines, antigen presentation, and cellular immunity. Because the modulation of immunity likely occurs at the site of first infection—the respiratory epithelium, we hypothesized that the mucosal influenza vaccine Flu Avert® I.N. (Flu Avert), which is known to stimulate strong antiviral responses, will enhance antiviral innate immunity, and that these responses would also provide protection from EHV-1 infection. To test our hypothesis, primary equine respiratory epithelial cells (ERECs) were treated with Flu Avert, and innate immunity was evaluated for 10 days following treatment. The timing of Flu Avert treatment was also evaluated for optimal effectiveness to reduce EHV-1 replication by modulating early immune responses to EHV-1. The induction of interferons, cytokine and chemokine mRNA expression, and protein secretion was evaluated by high-throughput qPCR and multiplex protein analysis. Intracellular and extracellular EHV-1 titers were determined by qPCR. Flu Avert treatment resulted in the modulation of IL-8, CCL2, and CXCL9 starting at days 5 and 6 post-treatment. Coinciding with the timing of optimal chemokine induction, our data also suggested the same timing for reduction of EHV-1 replication. In combination, our results suggest that Flu Avert may be effective at counteracting some of the immune-modulatory properties of EHV-1 at the airway epithelium and the peak for this response occurs 5–8 days post-Flu Avert treatment. Future in vivo studies are needed to investigate Flu Avert as a prophylactic in situations where EHV-1 exposure may occur.

scholarly journals Equine Herpesvirus 1 Utilizes a Novel Herpesvirus Entry Receptor

2005 ◽  
Vol 79 (5) ◽  
pp. 3169-3173 ◽  
Author(s):  
Arthur R. Frampton ◽  
William F. Goins ◽  
Justus B. Cohen ◽  
Jens von Einem ◽  
Nikolaus Osterrieder ◽  
...  
Keyword(s):  
Cell Surface ◽  
Equine Herpesvirus ◽  
Glycoprotein D ◽  
Equine Herpesvirus 1 ◽  
Herpesvirus 1 ◽  
Entry Receptor

ABSTRACT The well-described herpesvirus entry receptors HveA (TNFRSF14), HveB (nectin 2), and HveC (nectin 1) have been shown to mediate the entry of alphaherpesviruses. Our findings showed that the alphaherpesvirus equine herpesvirus 1 (EHV-1) efficiently entered and replicated in CHO-K1 cells that lack the entry receptors HveA, HveB, and HveC, demonstrating that EHV-1 utilizes a unique entry receptor. As with other alphaherpesviruses, efficient EHV-1 entry was dependent on glycoprotein D and cell surface glycosaminoglycans.

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