Combination Of Arsenic and Interferon-a Inhibits Expression Of KSHV Latent Transcripts and Synergistically Improves Survival Of Mice With Primary Effusion Lymphomas

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5154-5154
Author(s):  
Hiba El Hajj ◽  
Jihane Ali ◽  
Akram Ghantous ◽  
Dana Hodroj ◽  
Ahmad Daher ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Kaposi Sarcoma ◽  
Abdominal Distension ◽  
Malignant Ascites ◽  
Etiologic Agent ◽  
Immunodeficient Mice ◽  
Barr Virus ◽  
Epstein Barr ◽  
Primary Effusion Lymphomas

Abstract Background Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphomas (PEL). PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans. Methodology/Principal findings Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN) inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice. Conclusion/Significance These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients. Disclosures: No relevant conflicts of interest to declare.

Acute Pharyngitis: Etiology and Diagnosis

PEDIATRICS ◽  
1996 ◽  
Vol 97 (6) ◽  
pp. 949-954
Author(s):  
Alan L. Bisno
Keyword(s):  
Herpes Simplex ◽  
Influenza A ◽  
Epstein Barr Virus ◽  
Viral Infections ◽  
Clinical Manifestations ◽  
Acute Pharyngitis ◽  
Herpesvirus Type ◽  
Barr Virus ◽  
Epstein Barr

Acute pharyngitis may be caused by a wide variety of microbial agents (Table 1). The relative importance of each of these agents varies greatly depending on a number of epidemiologic factors, including age of the patient, season of the year, and geographic locale. Viruses Most cases of acute pharyngitis are viral in etiology and involve the pharynx as well as other portions of the respiratory tract as manifestations of the common cold, influenza, or croup. Examples include the rhinoviruses, coronaviruses, influenza A and B, and the parainfluenza viruses. Certain viral infections causing sore throat may exhibit clinical manifestations that are rather distinctive. Examples include enteroviruses (herpangina due to Coxsackie A), Epstein-Barr virus (infectious mononucleosis), cytomegalovirus (cytomegalovirus mononucleosis), adenovirus (pharyngoconjunctival fever, acute respiratory disease of military recruits), and herpes simplex virus (pharyngitis, gingivitis, and stomatitis). In many instances, however, the illnesses caused by these agents may overlap so broadly with that of streptococcal pharyngitis as to be clinically indistinguishable. Thus, Epstein-Barr virus, adenovirus, and herpes virus may all cause fever, exudative pharyngitis, and cervical adenitis. Several studies have documented the role of primary herpesvirus type 1 infection as a cause of acute pharyngitis in college students.1-4 Herpesvirus type 2 can occasionally cause a similar illness as a consequence of oral-genital sexual contact.5 Although herpesvirus infections may involve the anterior oral cavity (vesicular or ulcerative gingivostomatitis) as well as the posterior pharynx, they do not routinely do so. Only about one-fourth of students with culturally and serologically proven primary herpes simplex type 1 pharyngitis studied by Glezen et al,2 for example, had gingivostomatitis.

scholarly journals Clinical Warning of Hemophagocytic Syndrome Caused by Epstein-barr Virus

2020 ◽  
Author(s):  
Jinjin Shi ◽  
Chu Chu ◽  
Min Yu ◽  
Dandan Zhang ◽  
Yuqin Li ◽  
...  
Keyword(s):  
Laboratory Tests ◽  
Epstein Barr Virus ◽  
Hemophagocytic Syndrome ◽  
Clinical Manifestations ◽  
Prognostic Indicator ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ebv Dna ◽  
Epstein Barr ◽  
D Dimer

Abstract Objectives This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1-3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects’ clinical manifestations and laboratory tests were analyzed retrospectively. Results Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3+, CD4+, CD8+, NK, and CD3-CD19+ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 µg/L, the sensitivity and specificity of D-Dimer was 88.90% and 90.20%, respectively. Conclusion The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.

scholarly journals Determinants of Gammaherpesvirus Shedding in Saliva Among Ugandan Children and Their Mothers

2018 ◽  
Vol 218 (6) ◽  
pp. 892-900 ◽  
Author(s):  
Robert Newton ◽  
Nazzarena Labo ◽  
Katie Wakeham ◽  
Vickie Marshall ◽  
Romin Roshan ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Kaposi Sarcoma ◽  
Parasitic Infections ◽  
Viral Shedding ◽  
Barr Virus ◽  
Epstein Barr

Among Ugandan mother-child pairs, Epstein-Barr virus was more likely to be shed in saliva than Kaposi sarcoma–associated virus. Child’s sex and parasitic infections influenced viral shedding. Shedding of each virus was inversely related, suggesting an interaction between them.

scholarly journals Dangerous Liaisons: Gammaherpesvirus Subversion of the Immunoglobulin Repertoire

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 788
Author(s):  
Monika A. Zelazowska ◽  
Kevin McBride ◽  
Laurie T. Krug
Keyword(s):  
B Cells ◽  
Somatic Hypermutation ◽  
Adaptive Immune Response ◽  
Kaposi Sarcoma ◽  
Lymphoid Tissues ◽  
Barr Virus ◽  
Sequencing Technologies ◽  
Biologic Property ◽  
Epstein Barr ◽  
Immunoglobulin Repertoire

A common biologic property of the gammaherpesviruses Epstein–Barr Virus and Kaposi sarcoma herpesvirus is their use of B lymphocytes as a reservoir of latency in healthy individuals that can undergo oncogenic transformation later in life. Gammaherpesviruses (GHVs) employ an impressive arsenal of proteins and non-coding RNAs to reprogram lymphocytes for proliferative expansion. Within lymphoid tissues, the germinal center (GC) reaction is a hub of B cell proliferation and death. The goal of a GC is to generate and then select for a pool of immunoglobulin (Ig) genes that will provide a protective humoral adaptive immune response. B cells infected with GHVs are detected in GCs and bear the hallmark signatures of the mutagenic processes of somatic hypermutation and isotype class switching of the Ig genes. However, data also supports extrafollicular B cells as a reservoir engaged by GHVs. Next-generation sequencing technologies provide unprecedented detail of the Ig sequence that informs the natural history of infection at the single cell level. Here, we review recent reports from human and murine GHV systems that identify striking differences in the immunoglobulin repertoire of infected B cells compared to their uninfected counterparts. Implications for virus biology, GHV-associated cancers, and host immune dysfunction will be discussed.

scholarly journals The Role of Dendritic Cells in Immune Control and Vaccination against γ-Herpesviruses

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1125 ◽  
Author(s):  
Christian Münz
Keyword(s):  
Kaposi Sarcoma ◽  
Immune Control ◽  
Barr Virus ◽  
Persistent Infections ◽  
Cell Responses ◽  
Tumor Virus ◽  
Epstein Barr ◽  
Antigen Presenting ◽  
Adoptive Transfer Therapy

The two human oncogenic γ-herpesviruses, Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), are prototypic pathogens that are controlled by T cell responses. Despite their ubiquitous distribution, persistent infections and transforming potential, most carriers’ immune systems control them for life. Therefore, they serve as paradigms of how near-perfect cell-mediated immune control can be initiated and maintained for decades. Interestingly, EBV especially quite efficiently avoids dendritic cell (DC) activation, and little evidence exists that these most potent antigen-presenting cells of the human body are involved in the priming of immune control against this tumor virus. However, DCs can be harnessed therapeutically to expand virus-specific T cells for adoptive transfer therapy of patients with virus-associated malignancies and are also currently explored for vaccinations. Unfortunately, despite 55 and 25 years of research on EBV and KSHV, respectively, the priming of their immune control that belongs to the most robust and durable immune responses in humans still remains unclear.

Inhibition of NF-κB induces apoptosis of KSHV-infected primary effusion lymphoma cells

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2537-2542 ◽  
Author(s):  
Shannon A. Keller ◽  
Elaine J. Schattner ◽  
Ethel Cesarman
Keyword(s):  
Primary Effusion Lymphoma ◽  
Leukemia Virus ◽  
Human Lymphocytes ◽  
Kaposi Sarcoma ◽  
Irreversible Inhibitor ◽  
Mobility Shift ◽  
Lymphoma Cells ◽  
Barr Virus ◽  
Human T Cell ◽  
Epstein Barr

Abstract Kaposi sarcoma–associated herpesvirus (KSHV), or human herpervirus 8 (HHV-8), is a γ-herpesvirus that infects human lymphocytes and is associated with primary effusion lymphoma (PEL). Currently, the role of viral infection in the transformation of PEL cells is unknown. One possibility is that KSHV, like the lymphotropic viruses Epstein-Barr virus (EBV) and human T-cell leukemia virus I (HTLV-I), activates the transcription factor NF-κB to promote survival and proliferation of infected lymphocytes. To examine this possibility, we assessed NF-κB activity in KSHV-infected PEL cell lines and primary tumor specimens by electrophoretic mobility shift assay (EMSA). We observed that NF-κB is constitutively activated in all KSHV-infected lymphomas, and consists of 2 predominant complexes, p65/p50 heterodimers and p50/p50 homodimers. Inhibition experiments demonstrated that Bay 11-7082, an irreversible inhibitor of IκBα phosphorylation, completely and specifically abrogated the NF-κB/DNA binding in PEL cells. PEL cells treated with Bay 11 demonstrated down-regulation of the NF-κB inducible cytokine interleukin 6 (IL-6), and apoptosis. These results suggest that NF-κB activity is necessary for survival of KSHV-infected lymphoma cells, and that pharmacologic inhibition of NF-κB may be an effective treatment for PEL.

The Impact of Epstein Bar Virus On Hodgkin Lymphoma's Histopathological Patterns in Morocco

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4781-4781
Author(s):  
Soumaya Anoun ◽  
Sofia Marouane ◽  
Meryem Kabbali ◽  
Soumia Zamiati ◽  
Said Benchekroun ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Developed Countries ◽  
Histological Subtype ◽  
Male Predominance ◽  
Barr Virus ◽  
Ebv Infection ◽  
Hematoxylin Staining ◽  
Staining Protocol ◽  
Epstein Barr ◽  
The Impact

Abstract Abstract 4781 Background: In Morocco, improvement of living conditions and access to healthcare has increased life expectancy from 58 years in 1980 to 72 years in 2010. There has been a corresponding decrease in early childhood infections, including Epstein Barr virus (EBV) infection, which is associated with Hodgkin lymphoma (HL). Mixed cellularity (MC) was the most common histopathological subset of HL in Morocco. Prior studies have shown the shift to nodular sclerosis (NS) subset since 1998. Currently, the incidence of NS subtype is still predominant in our country. Our aim is to study the incidence of EBV infection in HL Moroccan population and correlate its decrease to explain the shift of HL histopathological pattern. Patients and methods: We compared children and adults with HL diagnosed during 3 periods: 1980–1995, 1998–2005 and 2010–2011 in the same university medical centre. All histological samples were prepared for examination by paraffin method, than stained by Hematoxylin staining protocol. Immunuhistochemical features of Hodgkin Reed Sternberg cells were performed to assess the expression of antibodies markers (CD30, CD15). The EBV profiling was identified by immunohistochemical stains for EBV latent membrane protein 1 (LMP-1) for the last periods. Statistical comparison of all the features was performed by Epi Info software. Results: The features of 1200 HL patients were enrolled. The average number of HL cases per year was 46 patients for the first period versus 74 patients for the last period. The mean age was respectively 24 years (range 2–64 years) for the first period, 32 years (range 2–60 years) for the second period and 34 years (range 3–76 years) for the third one. Sex-Ratio showed male predominance. The comparison of HL incidence through the age over the past 30 years is further characterized by a significant higher incidence in elderly patients (2% versus 10%), and lower incidence in young children (32% versus 7%). The expression of LMP1 in HRS is significantly reduced between the two last periods (P=0.001). LMP1 positivity is higher in patients under fifteen years than in young adults. Currently, NS is the most prevalent histological subtype with a significant increasing frequency through the three periods (p< 0.001) instead of MC subtype. (Table1). Conclusion: HL pattern in Morocco tends to be like in developed countries. The shift of HL histological subtype from CM to NS could be explained by the decrease of EBV infection in Hodgkin Reed Sternberg cells. More patients need to be enrolled to confirm this hypothesis Disclosures: No relevant conflicts of interest to declare.

Recombinant interferons in comprehensive therapy for new coronavirus infection

2020 ◽  
Vol 18 (3) ◽  
pp. 41-46
Author(s):  
E.V. Melekhina ◽  
◽  
S.V. Nikolaeva ◽  
A.S. Ilyinskaya ◽  
Zh.B. Ponezheva ◽  
...  
Keyword(s):  
Early Treatment ◽  
Epstein Barr Virus ◽  
Companion Animals ◽  
Clinical Manifestations ◽  
Upper Respiratory Tract ◽  
Recombinant Interferon ◽  
Barr Virus ◽  
Comprehensive Therapy ◽  
Coronavirus Infection ◽  
Epstein Barr

The second decade of the 21st century has brought us a new coronavirus infection, SARS-CoV-2, which affects not only animals (livestock, companion animals, birds), but also people, causing severe disease in them (COVID-19) with various clinical variants: from upper respiratory tract lesions to sepsis and thromboembolism. Coronaviruses are known to suppress the production of IFN-I. Therefore, administration of IFN-I is a promising strategy for early treatment and prevention of COVID-19. In the Russian Federation, treatment of COVID-19 in children is performed in accordance with the recommendations of the Ministry of Health of Russia and depends on the clinical form of the disease. Mild and moderate forms of the disease, observed in the majority of children, are treated according to the protocols for managing ARVI, bronchitis, bronchiolitis, and pneumonia in children. However, the fact that non-severe COVID-19 shares clinical manifestations with other infections caused by respiratory viruses and herpesviruses (including cytomegalovirus, HHV6A/B, and Epstein-Barr virus), as well as recently increased proportion of mixed viral infections necessitate (until the etiological diagnosis is confirmed) the administration of drugs recommended for the treatment of seasonal ARVI (including intranasal forms of IFN-α, etc.). Such therapeutic tactics often ensures faster improvement and symptom elimination. We report a case of mixed respiratory infection caused by two viruses (SARS-CoV-2 and Epstein–Barr virus) in a child. Early treatment with recombinant interferon-α2b with taurine resulted in fever alleviation and normalization of child’s condition by the moment of transfer to a specialized department. Key words: SARS-CoV-2, COVID-19, children, treatment, interferon.

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