scholarly journals Animal Models for Gammaherpesvirus Infections: Recent Development in the Analysis of Virus-Induced Pathogenesis

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 116 ◽  
Author(s):  
Shigeyoshi Fujiwara ◽  
Hiroyuki Nakamura
Keyword(s):  
Animal Models ◽  
Experimental Infection ◽  
Specific Treatment ◽  
Clinical Importance ◽  
Laboratory Animals ◽  
Human Immune System ◽  
Immunodeficient Mice ◽  
Barr Virus ◽  
Treatment And Prevention ◽  
Epstein Barr

Epstein–Barr virus (EBV) is involved in the pathogenesis of various lymphomas and carcinomas, whereas Kaposi’s sarcoma-associated herpesvirus (KSHV) participates in the pathogenesis of endothelial sarcoma and lymphomas. EBV and KSHV are responsible for 120,000 and 44,000 annual new cases of cancer, respectively. Despite this clinical importance, no chemotherapies or vaccines have been developed for virus-specific treatment and prevention of these viruses. Humans are the only natural host for both EBV and KSHV, and only a limited species of laboratory animals are susceptible to their experimental infection; this strict host tropism has hampered the development of their animal models and thereby impeded the study of therapeutic and prophylactic strategies. To overcome this difficulty, three main approaches have been used to develop animal models for human gammaherpesvirus infections. The first is experimental infection of laboratory animals with EBV or KSHV. New-world non-human primates (NHPs) and rabbits have been mainly used in this approach. The second is experimental infection of laboratory animals with their own inherent gammaherpesviruses. NHPs and mice have been mainly used here. The third, a recent trend, employs experimental infection of EBV or KSHV or both to immunodeficient mice reconstituted with human immune system components (humanized mice). This review will discuss how these three approaches have been used to reproduce human clinical conditions associated with gammaherpesviruses and to analyze the mechanisms of their pathogenesis.

Correction of Uroporphyrinogen Decarboxylase Deficiency (Hepatoerythropoietic Porphyria) in Epstein-Barr Virus-Transformed B-Cell Lines by Retrovirus-Mediated Gene Transfer: Fluorescence-Based Selection of Transduced Cells

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 465-474
Author(s):  
Antonio Fontanellas ◽  
Frédéric Mazurier ◽  
François Moreau-Gaudry ◽  
Francis Belloc ◽  
Cécile Ged ◽  
...  
Keyword(s):  
Gene Therapy ◽  
B Cell ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Uv Light ◽  
Specific Treatment ◽  
Uroporphyrinogen Decarboxylase ◽  
Immunodeficient Mice ◽  
Barr Virus ◽  
Epstein Barr

Hepatoerythropoietic porphyria (HEP) is an inherited metabolic disorder characterized by the accumulation of porphyrins resulting from a deficiency in uroporphyrinogen decarboxylase (UROD). This autosomal recessive disorder is severe, starting early in infancy with no specific treatment. Gene therapy would represent a great therapeutic improvement. Because hematopoietic cells are the target for somatic gene therapy in this porphyria, Epstein-Barr virus-transformed B-cell lines from patients with HEP provide a model system for the disease. Thus, retrovirus-mediated expression of UROD was used to restore enzymatic activity in B-cell lines from 3 HEP patients. The potential of gene therapy for the metabolic correction of the disease was demonstrated by a reduction of porphyrin accumulation to the normal level in deficient transduced cells. Mixed culture experiments demonstrated that there is no metabolic cross-correction of deficient cells by normal cells. However, the observation of cellular expansion in vitro and in vivo in immunodeficient mice suggested that genetically corrected cells have a competitive advantage. Finally, to facilitate future human gene therapy trials, we have developed a selection system based on the expression of the therapeutic gene. Genetically corrected cells are easily separated from deficient ones by the absence of fluorescence when illuminated under UV light.

Correction of Uroporphyrinogen Decarboxylase Deficiency (Hepatoerythropoietic Porphyria) in Epstein-Barr Virus-Transformed B-Cell Lines by Retrovirus-Mediated Gene Transfer: Fluorescence-Based Selection of Transduced Cells

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 465-474 ◽  
Author(s):  
Antonio Fontanellas ◽  
Frédéric Mazurier ◽  
François Moreau-Gaudry ◽  
Francis Belloc ◽  
Cécile Ged ◽  
...  
Keyword(s):  
Gene Therapy ◽  
B Cell ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Uv Light ◽  
Specific Treatment ◽  
Uroporphyrinogen Decarboxylase ◽  
Immunodeficient Mice ◽  
Barr Virus ◽  
Epstein Barr

Abstract Hepatoerythropoietic porphyria (HEP) is an inherited metabolic disorder characterized by the accumulation of porphyrins resulting from a deficiency in uroporphyrinogen decarboxylase (UROD). This autosomal recessive disorder is severe, starting early in infancy with no specific treatment. Gene therapy would represent a great therapeutic improvement. Because hematopoietic cells are the target for somatic gene therapy in this porphyria, Epstein-Barr virus-transformed B-cell lines from patients with HEP provide a model system for the disease. Thus, retrovirus-mediated expression of UROD was used to restore enzymatic activity in B-cell lines from 3 HEP patients. The potential of gene therapy for the metabolic correction of the disease was demonstrated by a reduction of porphyrin accumulation to the normal level in deficient transduced cells. Mixed culture experiments demonstrated that there is no metabolic cross-correction of deficient cells by normal cells. However, the observation of cellular expansion in vitro and in vivo in immunodeficient mice suggested that genetically corrected cells have a competitive advantage. Finally, to facilitate future human gene therapy trials, we have developed a selection system based on the expression of the therapeutic gene. Genetically corrected cells are easily separated from deficient ones by the absence of fluorescence when illuminated under UV light.

scholarly journals Three Severe Cases of Viral Infections with Post-Kidney Transplantation Successfully Confirmed by Polymerase Chain Reaction and Flow Cytometry

2018 ◽  
Vol 8 (3) ◽  
pp. 198-206
Author(s):  
Keita Nakanishi ◽  
Hiroshi Kaito ◽  
Miki Ogi ◽  
Denshi Takai ◽  
Junya Fujimura ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Polymerase Chain Reaction ◽  
Kidney Transplantation ◽  
Viral Infections ◽  
Specific Treatment ◽  
Epstein Barr Virus Infection ◽  
Chain Reaction ◽  
Barr Virus ◽  
Polymerase Chain ◽  
Epstein Barr

Viral infections in patients with post-kidney transplantation are often difficult to diagnose as well as treat. We herein report three cases with severe viral infections after kidney transplantation. All their causative pathogens could be detected promptly by polymerase chain reaction and flow cytometry during the early stages of infection. These examinations would also be of great use to monitor therapeutic responses and disease activity. It is indeed true that no specific treatment is available for most of the viral infections, but we should be aware that some infections, such as Epstein-Barr virus infection, can be treatable with prompt and specific treatment, such as rituximab.

Myocarditis: aetiology and histopathological diagnosis

ESC CardioMed ◽  
2018 ◽  
pp. 1512-1515
Author(s):  
Sabine Pankuweit
Keyword(s):  
Parvovirus B19 ◽  
Specific Treatment ◽  
Influenza Viruses ◽  
Histopathological Diagnosis ◽  
Cardiac Tissues ◽  
Barr Virus ◽  
Reverse Transcription Pcr ◽  
Epstein Barr ◽  
Inflammatory Infiltrates ◽  
Infiltrating Lymphocytes

Although the aetiology of myocarditis in a given patient often remains unknown, a large variety of infectious agents, including viruses, bacteria, protozoa, and fungi, systemic and autoimmune diseases, drugs, and toxins can cause myocarditis. The diagnosis of myocarditis is complex and challenging. The diagnostic gold standard is endomyocardial biopsy in which myocarditis is defined using the histological Dallas criteria and immunohistochemistry. Current diagnostic criteria require more than 14 infiltrating lymphocytes/mm2 (up to 4 macrophages may be included with the presence of CD3-positive T lymphocytes ≥7 cells/mm2). Inflammatory infiltrates are subdivided into lymphocytic, eosinophilic, polymorphic, giant cell, and cardiac sarcoidosis as these diagnoses imply a specific treatment and prognosis. Molecular biological analyses of cardiac tissues should include real-time polymerase chain reaction (PCR) and reverse transcription PCR assays for the most common cardiotropic infectious viruses such as enteroviruses, adenoviruses, cytomegalovirus, influenza viruses, human herpes virus 6, Epstein–Barr virus, hepatitis C virus, and parvovirus B19.

scholarly journals Plasma Nucleic Acids in the Diagnosis and Management of Malignant Disease

2002 ◽  
Vol 48 (8) ◽  
pp. 1186-1193 ◽  
Author(s):  
Philip J Johnson ◽  
YM Dennis Lo
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Clinical Importance ◽  
Barr Virus ◽  
Circulating Nucleic Acids ◽  
Clinical Relationship ◽  
Malignant State ◽  
Cancer Types ◽  
Epstein Barr ◽  
Near Future

Abstract Background: There is a need for development of molecular markers of cancer that can be used clinically for the detection, prognostication, and monitoring of cancer. Recently, there has been much interest in the potential use of nucleic acid markers in plasma and serum for this purpose. Approach: We reviewed published literature up to 2002 on the topic, with a particular emphasis on reports published between 1996 and 2002. Content: The nucleic acid markers described in plasma and serum include oncogene mutations/amplifications, microsatellite alterations, and gene rearrangements. Such markers have been described in many cancer types, including lung, colon, and breast. Epigenetic alterations, such as aberrant promoter methylation, have been identified in plasma and serum. Viral nucleic acid markers, such as Epstein–Barr virus DNA in plasma and serum, are reviewed in detail with regard to their application to virus-associated cancers such as nasopharyngeal carcinoma and various lymphomas. More recently, mitochondrial DNA and tumor-related mRNAs have been identified in plasma and serum from patients with several types of tumors. Conclusions: Circulating nucleic acids are an emerging class of molecular tumor markers. Their wide applicability and clinical relationship with the malignant state will likely grant them increasing clinical importance in the near future.

scholarly journals Cytochemical, cytogenetic, immunophenotypic and tumorigenic characterization of two hairy cell lines

Blood ◽  
1988 ◽  
Vol 71 (2) ◽  
pp. 422-429
Author(s):  
GB Faguet ◽  
KL Satya-Prakash ◽  
JF Agee
Keyword(s):  
Cell Lines ◽  
Nuclear Antigen ◽  
Small Subset ◽  
Tartrate Resistant Acid Phosphatase ◽  
Hairy Cell ◽  
Primary Tumors ◽  
Immunodeficient Mice ◽  
Barr Virus ◽  
Epstein Barr ◽  
B Lineage

Two cell lines (EH and HK) were derived from two patients with hairy cell leukemia (HCL). Both patients exhibited a clinical picture characteristic of HCL, including splenomegaly, cytopenias, and tartrate- resistant acid phosphatase (TRAP)-positive “hairy” lymphocytes in blood and marrow. EH and HK were demonstrably of B lineage, as judged by cytochemistry and immunophenotype, including expression of B1, B2, and LEU-12 antigens and of monoclonal surface immunoglobulins (slgs). Monoclonality was confirmed by clonal karyotype abnormality demonstrated in cell line HK. HCL parentage suggested by cytochemistry and electron microscopy was confirmed by the immunophenotypic observation that HCL lines expressed antigens alpha S-HCL1, alpha S- HCL3, and cCLLa. While alpha S-HCL1 and alpha S-HCL3 are nonspecific, their co-expression is characteristic of HCL cells. The cCLLa is a novel 69-kd membrane HCL-associated polypeptide antigen not shared by circulating normal T or B lymphocytes nor by malignant cells from unrelated lymphoid or nonlymphoid malignancies. The doubling time of EH and HK was 24 and 36 hours, respectively. While HK included a small subset of Epstein-Barr virus (EBV) nuclear antigen-positive cells, EH cells were homogeneously negative for the presence of this antigen. Both cell lines were consistently implantable in irradiation- preconditioned immunodeficient mice giving rise to primary tumors and widespread metastasis.

scholarly journals Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 1231-1239 ◽  
Author(s):  
Cagan Gurer ◽  
Till Strowig ◽  
Fabienne Brilot ◽  
Maggi Pack ◽  
Christine Trumpfheller ◽  
...  
Keyword(s):  
T Cells ◽  
Epstein Barr Virus ◽  
Poly I:C ◽  
Nuclear Antigen ◽  
Human Immune System ◽  
Proliferating Cells ◽  
Mhc I ◽  
Barr Virus ◽  
Epstein Barr

Abstract Dendritic cells (DCs) express many endocytic receptors that deliver antigens for major histocompatibility class (MHC) I and II presentation to CD8+ and CD4+ T cells, respectively. Here, we show that targeting Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) to one of them, the human multilectin DEC-205 receptor, in the presence of the DC maturation stimulus poly(I:C), expanded EBNA1-specific CD4+ and CD8+ memory T cells, and these lymphocytes could control the outgrowth of autologous EBV-infected B cells in vitro. In addition, using a novel mouse model with reconstituted human immune system components, we demonstrated that vaccination with αDEC-205-EBNA1 antibodies primed EBNA1-specific IFN-γ–secreting T cells and also induced anti-EBNA1 antibodies in a subset of immunized mice. Because EBNA1 is the one EBV antigen that is expressed in all proliferating cells infected with this virus, our data suggest that DEC-205 targeting should be explored as a vaccination approach against symptomatic primary EBV infection and against EBV-associated malignancies.

scholarly journals Linfohistiocitose Hemofagocítica Secundária a Infeção por Epstein-Barr: Raridade e Gravidade num Adulto Imunocompetente

2019 ◽  
Vol 32 (1) ◽  
pp. 78
Author(s):  
Andreia Sofia Costa ◽  
Anusca Paixão ◽  
Henrique Santos ◽  
Fernando Salvador
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Epstein Barr Virus ◽  
Clinical Case ◽  
Specific Treatment ◽  
Supportive Therapy ◽  
Intravascular Coagulation ◽  
Barr Virus ◽  
Life Threatening ◽  
Epstein Barr

Hemophagocytic lymphohistiocytosis is a rare, aggressive and life-threatening syndrome, characterized by an excessive immune activation. It is triggered by multiple stimuli, with infections having an important role. The most common infectious trigger is viral infection, particularly by Epstein-Barr virus. Coagulation disorders are common in hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation can be present in severe cases. We report a clinical case of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis, complicated with disseminated intravascular coagulation which evolved favorably with only supportive therapy and without specific treatment.

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