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1.
Oral Dis ; 26 Suppl 1: 158-160, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32862526

RESUMO

We present three cases of oral hairy leukoplakia (OHL) in whom the diagnosis was established by EBV DNA detection in whole saliva. Three HIV-infected patients came to the Oral Medicine Clinic with similar chief complaints of asymptomatic white lesions on the tongue. All patients were diagnosed with suspected OHL and oral thrush also in the first patient. A multiplex PCR DNA microarray was performed to detect EBV DNA in saliva collected by spitting method. All saliva samples showed positive results for EBV DNA, and the definitive diagnosis of OHL was made. Resolution of lesions was found at 1- to 2-month follow-up after treatment with application of acyclovir 5% cream 5 times daily. Additionally, anti-fungal treatment was given to the first patient and anti-retroviral treatment to the first and second patients. EBV is mostly transmitted by asymptomatic shedding into saliva. Therefore, the detection of salivary EBV DNA is useful in establishing a definitive diagnosis of OHL allowing more effective treatment for both HIV-infected patients receiving ART and treatment-naïve patients at any CD4 + count.


Assuntos
Soropositividade para HIV , HIV-1 , Herpesvirus Humano 4 , Leucoplasia Pilosa , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Leucoplasia Pilosa/diagnóstico , Leucoplasia Pilosa/virologia , Leucoplasia Oral , Saliva
2.
PLoS One ; 15(8): e0236896, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745119

RESUMO

Single-stranded DNA binding protein 2 (SSBP2) is ubiquitously expressed, with several studies reporting it to be a tumor suppressor. We investigated SSBP2 expression and its clinicopathological significance in gastric cancer. SSBP2 expression was examined by immunohistochemistry in 539 gastric cancer sections. The cases were divided into three subtypes, namely, Epstein-Barr virus-associated (EBV), microsatellite unstable, and others (microsatellite stable and EBV negative), based on the molecular classification of The Cancer Genome Atlas (TCGA). Cases were also divided into two subgroups according to the amplification status of human epidermal growth factor receptor 2 (HER2). Most cases showed SSBP2 positivity, and only 24 (4.5%) cases displayed negative nuclear expression. Loss of nuclear expression correlated significantly with high pT category (P = 0.001), nodal metastasis (P = 0.002), and stage of progression (P = 0.005), with no correlation between molecular characteristics and SSBP2 expression. All HER2 amplification cases displayed positive SSBP2 expression. Negative SSBP2 cases showed significantly shorter recurrence-free survival (RFS) compared to positive SSBP2 cases (P = 0.008). Loss of nuclear expression of SSBP2 was significantly associated with shorter RFS in the microsatellite stable and EBV negative groups (P = 0.002), as well as the HER2 negative group (P = 0.007). However, there were no statistically significant differences in multivariate analyses. Loss of nuclear expression of SSBP2 was a poor prognostic factor, associated with stage of progression and recurrence, and showed no significant difference in molecular characteristics, including TCGA subtype and HER2 status.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Receptor ErbB-2/genética , Neoplasias Gástricas , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/genética , Feminino , Expressão Gênica , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
3.
J Investig Med High Impact Case Rep ; 8: 2324709620950107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32787459

RESUMO

Hemophagocytic lymphohistocytosis (HLH) is a hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, and pancytopenia. It may be associated with genetic mutations or viral/bacterial infections, most commonly Epstein-Barr virus (EBV) and cytomegalovirus. As for the novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also known as COVID-19 (coronavirus disease-2019), the cytokine storm it triggers can theoretically lead to syndromes similar to HLH. In this article, we report a case of a 28-year-old female who presented with high-grade fevers, found to have both SARS-CoV-2 and EBV infections, and eventually began to show signs of early HLH. To our knowledge, this is the first case reported in literature that raises the possibility of SARS-CoV-2-related HLH development.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/isolamento & purificação , Linfo-Histiocitose Hemofagocítica/imunologia , Pneumonia Viral/complicações , Adulto , Infecções por Coronavirus/diagnóstico , Infecções por Vírus Epstein-Barr/complicações , Feminino , Humanos , Pandemias , Pneumonia Viral/diagnóstico
4.
Ann Hematol ; 99(7): 1575-1581, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32500223

RESUMO

This study investigated the clinical characteristics of Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis (HLH-HL). Clinical data of 8 patients with HLH-HL and 20 non-HLH-HL patients were included. All eight HLH-HL patients tested positive for plasma Epstein-Barr virus (EBV)-DNA and EBV-encoded small RNA (EBER), and six patients were positive for EBV-DNA in the peripheral blood mononuclear cells (PBMCs). Two out of the 20 non-HLH-HL patients were confirmed positive for EBER, and the remaining 18 patients were negative. Among the HLH-HL patients, five patients received ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) chemotherapy regimens in other hospitals, and their conditions were considered to be worse, for which reason they were transferred to our center, and three patients were treated with DEP (doxorubicin-etoposide-methylprednisolone) regimens to target HLH and were alive as of the writing of this article. Two patients were critically ill upon admission and were not able to undergo chemotherapy. Significant differences in survival time were observed between the HLH-HL and non-HLH-HL patients (P = 0.005). HL patients found positive for EBV (plasma/PBMCs EBV-DNA(+)/EBER(+)) may be more likely to develop HLH-HL. It may be beneficial to target HLH during the acute phase of HLH, followed by treating HL once the HLH condition has stabilized. HLH-HL patients have worse prognosis and higher mortality than non-HLH-HL patients.


Assuntos
Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Estudos de Casos e Controles , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Etoposídeo/uso terapêutico , Feminino , Herpesvirus Humano 4/isolamento & purificação , Doença de Hodgkin/sangue , Doença de Hodgkin/complicações , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/complicações , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vimblastina/uso terapêutico , Adulto Jovem
5.
PLoS One ; 15(5): e0232474, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374757

RESUMO

BACKGROUND: In Brazil, penile cancer (PC) is not uncommon. The highest incidence of PC is in the North and Northeast of the country. In addition to phimosis, the Human Papillomavirus (HPV) and Epstein-Baar Virus (EBV) infections are also related as risk factors for PC. The overexpression of p16INK4a is a surrogate sensitive marker of HPV infection in PC. OBJECTIVES: To correlate p16INK4a overexpression and HPV infection status with EBV infection in a series of PC patients from the Amazon region. METHODS: Tumor tissues from 47 PC cases were analyzed for the presence of HPV and EBV DNA by PCR. All PC patients were diagnosed between 2013 and 2018 at a public reference cancer center hospital in Manaus, Amazonas-Brazil. HPV was genotyped using E7 HPV16/HPV18 type-specific real-time PCR and the PapilloCheck® HPV-Screening assay. p16INK4a expression was evaluated by immunohistochemistry using the automated Ventana® BenchMark Ultra. RESULTS: The mean age of patients at the time of diagnosis was 57.4 years ±SD 17.8 ranging from 20 to 90 years old. Most of the patients (64%) came from rural areas of the Amazonas State. Thirty patients had phimosis (64%). Among the patients with phimosis, 43% (13/30) underwent circumcision, three during childhood and 10 in adulthood. 60% of the patients were smokers or ex-smokers. HPV infection was observed in 45% (21/47) of cases. HPV16 was detected in 13 patients (61%). Other HPV types detected were HPV 6, 11, 42, 51, 53, 68 and 44/55. EBV infection was observed in 30% (14/47) of the patients with PC. Co-infection with HPV and EBV was observed in 28% (6/21) cases. p16INK4a was only investigated in 26 samples. The p16INK4a overexpression was observed exclusively in HPV 16 positive cases and four HPV negative cases. In the survival analysis, the follow-up time was 35.4 months/patient. The mortality rate during the follow up time was 38%. CONCLUSIONS: p16INK4a positivity presented a high correlation to HPV 16 DNA detection, reinforcing its use as a surrogate marker for HPV-driven cancers. Infection with EBV was quite frequent and its role in epithelial penile oncogenesis needs to be demonstrated.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Infecções por Vírus Epstein-Barr/complicações , Papillomaviridae , Infecções por Papillomavirus/complicações , Neoplasias Penianas/etiologia , Neoplasias Penianas/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , DNA Viral/genética , DNA Viral/isolamento & purificação , Infecções por Vírus Epstein-Barr/virologia , Marcadores Genéticos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/patogenicidade , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/patogenicidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Neoplasias Penianas/epidemiologia , Fatores de Risco , Regulação para Cima , Adulto Jovem
6.
J Cancer Res Ther ; 16(1): 167-169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362630

RESUMO

Lymphoproliferative malignancies can involve both nodal- and extra-nodal tissues. The most common extranodal site involved is the gastrointestinal (GI) tract, and it is secondary to the widespread primary nodal disease. However, about 33% of non-Hodgkin's lymphoma primarily arise from tissues other than lymph nodes, spleen, or bone marrow, for example, GI tract, skin, or the central nervous system and are called primary extranodal lymphomas. The most common site of GI localization is stomach (50%-60%) followed by small bowel. Primary colonic lymphoma is seen only in 6% of GI lymphomas and up to 0.5%-1% of all colon malignancies. Hence, primary GI lymphoma is extremely rare, and primary colonic lymphoma is an even rarer occurrence. There is clearly a paucity of cases reported in literature resulting in unclear treatment protocol. Here, we report a case of a 51-year-old man who presented with abdominal pain, weight loss, and bright red blood per rectum. A colonoscopy revealed diffuse bleeding ulcers involving the entire colon. Pathology was consistent with primary diffuse large B-cell lymphoma arising from the colon. The patient was started on treatment with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone.


Assuntos
Neoplasias do Colo/virologia , Infecções por Vírus Epstein-Barr/complicações , Hemorragia Gastrointestinal/virologia , Herpesvirus Humano 4/isolamento & purificação , Linfoma Difuso de Grandes Células B/virologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Infecções por Vírus Epstein-Barr/virologia , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/patologia , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Prognóstico
7.
Cancer Immunol Immunother ; 69(8): 1615-1626, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32314041

RESUMO

BACKGROUND: The etiological role of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is confirmed. However, the role of other oncoviruses in OPSCC is unknown. MATERIALS AND METHODS: A total of 158 consecutive OPSCC patients treated with curative intent were included. DNA extracted from tumor sections was used to detect Epstein-Barr virus (EBV), HPV, and the following polyomaviruses: John Cunningham virus (JCV), Simian virus 40 (SV40), and BK virus (BKV) with PCR. In addition, p16 expression was studied by immunohistochemistry, and EBV-encoded small RNA (EBER) transcripts were localized by in situ hybridization. The effect of viral status on overall survival (OS) and disease-free survival (DFS) was analyzed. RESULTS: A total of 94/158 samples (59.5%) were HPV-positive, 29.1% contained BKV DNA, 20.3% EBV DNA, 13.9% JCV DNA, and 0.6% SV40 DNA. EBER was expressed only in stromal lymphocytes adjacent to the tumor and correlated with HPV positivity (p = 0.026). p16 expression associated only with HPV. None of the three polyomaviruses had an impact on survival. Patients with EBER-positive but HPV-negative OPSCC had significantly poorer OS and DFS than those with HPV-positive OPSCC and slightly worse prognosis compared with the patients with EBER-negative and HPV-negative OPSCC. CONCLUSION: Polyomaviruses are detectable in OPSCC but seem to have no impact on survival, whereas HPV was the strongest viral prognostic factor. EBER expression, as a sign of latent EBV infection, may have prognostic impact among patients with HPV-negative OPSCC. EBER analysis may identify a new subgroup of OPSCCs unrelated to HPV.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Neoplasias Orofaríngeas/virologia , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/complicações , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/metabolismo , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Polyomavirus/isolamento & purificação , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/virologia , Prognóstico , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/virologia
8.
Ann Hematol ; 99(10): 2243-2253, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32307569

RESUMO

Germinotropic lymphoproliferative disorder is a rare and rather enigmatic novel entity with distinctive clinicopathological features, one of which is the typical co-infection by Human herpesvirus 8 and Epstein-Barr virus. Human herpesvirus 8 is a lymphotropic virus detected in Kaposi sarcoma, multicentric Castleman disease, primary effusion lymphoma, Human herpesvirus 8-positive diffuse large B cell lymphoma not otherwise specified, and germinotropic lymphoproliferative disorder. Co-infection by Human herpesvirus 8 and Epstein-Barr virus is identified only in two lymphoproliferative diseases: germinotropic lymphoproliferative disorder and primary effusion lymphoma, which are otherwise diseases with totally different clinical presentations and outcomes. Unlike primary effusion lymphoma mostly occurring in immunocompromised individuals and following an aggressive course, germinotropic lymphoproliferative disorder usually presents with single or multiple lymphadenopathy affecting mainly immunocompetent individuals and mostly follows an indolent course. Based on the PRISMA guidelines, we carried out a systematic search on PubMed/MEDLINE, Web of Science, Scopus, EMBASE, and Cochrane Library using the search terms "germinotropic" and "lymphoproliferative disorder." Current scientific literature reports just 19 cases of germinotropic lymphoproliferative disorder. The purpose of our systematic review is to improve our understanding of the disease, focusing on epidemiology, clinical presentation, pathological features, treatment, and outcome. In addition, we discuss the differential diagnosis with the other Human herpesvirus 8-related lymphoproliferative diseases as currently recognized in the World Health Organization classification, adding a focus on lymphoproliferative disorders showing overlapping features.


Assuntos
Coinfecção/virologia , Infecções por Herpesviridae/virologia , Herpesvirus Humano 4/patogenicidade , Herpesvirus Humano 8/patogenicidade , Transtornos Linfoproliferativos/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Diagnóstico Diferencial , Progressão da Doença , Feminino , Centro Germinativo/patologia , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/terapia , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 8/isolamento & purificação , Humanos , Imunocompetência , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/virologia , Linfoma não Hodgkin/virologia , Linfoma de Efusão Primária/diagnóstico , Linfoma de Efusão Primária/virologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
9.
Cancer Causes Control ; 31(4): 365-375, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32112173

RESUMO

PURPOSE: Although infection with high-risk human papillomavirus (HPV) is a prerequisite for cervical cancer development, HPV infection is not sufficient to promote cancer in the majority of infected women. We tested the hypothesis that human herpesviruses might cooperate with HPV to promote the development of cervical dysplasia, an early indicator of cervical cancer development. METHODS: This study used archived specimens from a cohort of human immunodeficiency virus (HIV)-seropositive women seeking gynecological care at the Medical Center of New Orleans, Louisiana. Viral DNA was detected by PCR amplification and risk of abnormal cervical cytology was determined in relation to virus test results. RESULTS: Consensus human herpesvirus PCR with herpes speciation by restriction endonuclease digestion revealed Epstein-Barr virus (EBV) to be the most prevalent herpesvirus in cervicovaginal lavage specimens. Further analysis using an EBV-specific PCR assay and cervical swab specimens demonstrated an approximately fourfold increased risk of abnormal cervical cytology in women testing positive for cervical EBV and high-risk HPV compared to women testing positive for high-risk HPV alone. This relationship was independent of markers of advancing HIV disease. CONCLUSION: Cervical shedding of EBV appears to predict a greater risk of cervical dysplasia in HIV-infected women with a high-risk HPV infection.


Assuntos
Infecções por Vírus Epstein-Barr/patologia , Infecções por HIV/patologia , Herpesvirus Humano 4/isolamento & purificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Displasia do Colo do Útero/virologia , Adulto , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Estudos de Coortes , DNA Viral/análise , DNA Viral/genética , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Infecções por HIV/virologia , Herpesvirus Humano 4/genética , Humanos , Louisiana/epidemiologia , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
10.
PLoS One ; 15(3): e0230374, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210468

RESUMO

Oxidative stress is suggested to be the crucial factor in diabetes mellitus type 2 (DM2) pathogenesis and in the development of diabetic complications. Patients with DM2 may be more susceptible to infections due to hyperglycaemia-induced virulence of various microorganisms. Several studies pointed that Epstein-Barr virus (EBV) infection is associated with reactive oxygen species (ROS) production and/or activation of signalling pathways connected with ROS. The present study analyzed serum activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in DM2 patients with and without EBV infection. Blood and saliva were collected from 120 patients with DM2. EBV DNA was detected in the saliva using nested-PCR technique. Spectrophotometric methods were implemented to determine serum GPx and SOD activity with the use of diagnostic kits produced by Randox Laboratories. GPx and SOD activity was decreased in diabetic patients, with the lowest values in DM2 EBV-positive patients. There was correlation between GPx and SOD activity-with increased value of GPx, SOD activity was also rised. In patients with DM2 history longer than 10 years as well as in DM2 patients with obesity, antioxidant enzymes activity was decreased. Determination of examined parameters may be useful in diabetic patients with EBV infection and could be important prognostic factor.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Infecções por Vírus Epstein-Barr/sangue , Glutationa Peroxidase/sangue , Herpesvirus Humano 4/isolamento & purificação , Superóxido Dismutase/sangue , Adulto , DNA Viral/isolamento & purificação , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Estudos de Viabilidade , Feminino , Glutationa Peroxidase/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/imunologia , Prognóstico , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/imunologia , Superóxido Dismutase/metabolismo , Adulto Jovem
11.
Blood ; 135(16): 1344-1352, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32107539

RESUMO

Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus (EBV)-driven B-cell lymphoproliferative disease (LPD). This disease is hypothesized to result from defective immune surveillance of EBV, with most patients showing evidence of immune dysfunction, despite no known primary immunodeficiency. Pathologically, LYG is graded by the number and density of EBV+ atypical B cells, and other characteristic findings include an angioinvasive/angiodestructive reactive T-cell infiltrate and various degrees of necrosis. Clinically, LYG universally involves the lungs with other common extranodal sites, including skin, central nervous system, liver, and kidneys. Nodal and/or bone marrow involvement is extremely rare and, if present, suggests an alternative diagnosis. Treatment selection is based on histologic grade and underlying pathobiology with low-grade disease hypothesized to be immune-dependent and typically polyclonal and high-grade disease to be immune-independent and typically oligoclonal or monoclonal. Methods of augmenting the immune response to EBV in low-grade LYG include treatment with interferon-α2b, whereas high-grade disease requires immunochemotherapy. Given the underlying defective immune surveillance of EBV, patients with high-grade disease may have a recurrence in the form of low-grade disease after immunochemotherapy, and those with low-grade disease may progress to high-grade disease after immune modulation, which can be effectively managed with crossover treatment. In patients with primary refractory disease or in those with multiple relapses, hematopoietic stem cell transplantation may be considered, but its efficacy is not well established. This review discusses the pathogenesis of LYG and highlights distinct histopathologic and clinical features that distinguish this disorder from other EBV+ B-cell LPDs and lymphomas. Treatment options, including immune modulation and combination immunochemotherapy, are discussed.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Granulomatose Linfomatoide/terapia , Granulomatose Linfomatoide/virologia , Animais , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imunoterapia , Granulomatose Linfomatoide/diagnóstico , Granulomatose Linfomatoide/patologia , Terapia de Alvo Molecular
12.
J Virol ; 94(10)2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32102884

RESUMO

The Epstein-Barr virus (EBV) causes human cancers, and epidemiological studies have shown that lytic replication is a risk factor for some of these tumors. This fits with the observation that EBV M81, which was isolated from a Chinese patient with nasopharyngeal carcinoma, induces potent virus production and increases the risk of genetic instability in infected B cells. To find out whether this property extends to viruses found in other parts of the world, we investigated 22 viruses isolated from Western patients. While one-third of the viruses hardly replicated, the remaining viruses showed variable levels of replication, with three isolates replicating at levels close to that of M81 in B cells. We cloned one strongly replicating virus into a bacterial artificial chromosome (BAC); the resulting recombinant virus (MSHJ) retained the properties of its nonrecombinant counterpart and showed similarities to M81, undergoing lytic replication in vitro and in vivo after 3 weeks of latency. In contrast, B cells infected with the nonreplicating Western B95-8 virus showed early but abortive replication accompanied by cytoplasmic BZLF1 expression. Sequencing confirmed that rMSHJ is a Western virus, being genetically much closer to B95-8 than to M81. Spontaneous replication in rM81- and rMSHJ-infected B cells was dependent on phosphorylated Btk and was inhibited by exposure to ibrutinib, opening the way to clinical intervention in patients with abnormal EBV replication. As rMSHJ contains the complete EBV genome and induces lytic replication in infected B cells, it is ideal to perform genetic analyses of all viral functions in Western strains and their associated diseases.IMPORTANCE The Epstein-Barr virus (EBV) infects the majority of the world population but causes different diseases in different countries. Evidence that lytic replication, the process that leads to new virus progeny, is linked to cancer development is accumulating. Indeed, viruses such as M81 that were isolated from Far Eastern nasopharyngeal carcinomas replicate strongly in B cells. We show here that some viruses isolated from Western patients, including the MSHJ strain, share this property. Moreover, replication of both M81 and of MSHJ was sensitive to ibrutinib, a commonly used drug, thereby opening an opportunity for therapeutic intervention. Sequencing of MSHJ showed that this virus is quite distant from M81 and is much closer to nonreplicating Western viruses. We conclude that Western EBV strains are heterogeneous, with some viruses being able to replicate more strongly and therefore being potentially more pathogenic than others, and that the virus sequence information alone cannot predict this property.


Assuntos
Linfócitos B/virologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Replicação Viral/fisiologia , Animais , Linfócitos B/patologia , Linhagem Celular , Clonagem Molecular , DNA Viral , Modelos Animais de Doenças , Genoma Viral , Células HEK293 , Herpesvirus Humano 4/crescimento & desenvolvimento , Herpesvirus Humano 4/isolamento & purificação , Humanos , Neoplasias Nasofaríngeas/virologia , Transativadores/genética
13.
Int J Infect Dis ; 93: 139-145, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32004689

RESUMO

BACKGROUND: In developing countries, Epstein-Barr virus (EBV) infection is mostly asymptomatic in early childhood. EBV persistence may lead to different malignancies, such as B cell derived lymphomas. In Argentina, most children are seropositive at three years and an increased association between EBV and lymphoma was proved in children under 10 years old by our group. OBJECTIVE: Our aim was to characterize EBV infection at the site of entry and reactivation of viral infection -the tonsils- in order to better understand the mechanism of viral persistence in pediatric patients. METHODS: A cohort of 54 patients was described. We assessed specific antibodies profiles in sera; viral proteins presence by IHC on FFPE samples and EBV type from fresh tissue. RESULTS: EBV type 1 was prevalent, mostly in the youngest patients. Asymptomatic primary infected patients presented higher viral loads and Latency 0/I or II patterns, whereas the Latency III pattern was observed mostly in healthy carriers. There were no differences between groups in the expression of viral lytic antigens. This study discloses new features in patients undergoing primary infection from a developing population. Low viral inoculum and restricted viral antigen expression may be responsible for the lack of symptoms in children from our country.


Assuntos
Infecções por Vírus Epstein-Barr/virologia , Adolescente , Anticorpos Antivirais/sangue , Antígenos Virais/metabolismo , Argentina , Criança , Pré-Escolar , Países em Desenvolvimento , Feminino , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/metabolismo , Humanos , Lactente , Masculino , Tonsila Palatina/virologia , Carga Viral , Proteínas Virais/metabolismo , Latência Viral
15.
Sci Rep ; 10(1): 193, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932685

RESUMO

Translating the findings of genome wide association studies (GWAS) to new therapies requires identification of the relevant immunological contexts to interrogate for genetic effects. In one of the largest GWAS, more than 200 risk loci have been identified for Multiple Sclerosis (MS) susceptibility. Infection with Epstein-Barr virus (EBV) appears to be necessary for the development of Multiple Sclerosis (MS). Many MS risk loci are associated with altered gene expression in EBV infected B cells (LCLs). We have interrogated this immunological context to identify interaction between MS risk loci and EBV DNA copy number, intrinsic growth rate and EBV encoded miRNA expression. The EBV DNA copy number was associated with significantly more risk alleles for MS than for other diseases or traits. EBV miRNAs BART4-3p and BART3-5p were highly associated with EBV DNA copy number and MS risk loci. The poliovirus receptor (PVR) risk SNP was associated with EBV DNA copy number, PVR and miRNA expression. Targeting EBV miRNAs BART4-3p and BART3-5p, and the gene PVR, may provide therapeutic benefit in MS. This study also indicates how immunological context and risk loci interactions can be exploited to validate and develop novel therapeutic approaches.


Assuntos
Variações do Número de Cópias de DNA , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Interações Hospedeiro-Patógeno/genética , Esclerose Múltipla/patologia , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Estudos de Coortes , DNA Viral/análise , DNA Viral/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Herpesvirus Humano 4/isolamento & purificação , Humanos , MicroRNAs/genética , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/virologia , Fenótipo
16.
Mol Biol Rep ; 47(3): 1803-1807, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31993862

RESUMO

Epstein-Barr virus (EBV) is a member of the γ herpesvirus subfamily. It is widely spread, potentially oncogenic and has been studied in different human cancers such as gastric carcinoma, nasopharyngeal carcinoma and both Hodgkin's and non-Hodgkin's lymphomas. EBV replicates in the oral epithelium, and resting B lymphocytes trafficking through the pharynx develop a latent infection in which only EBV genes related to the B cell growth program are expressed: LMP1, -2a/b, BARTs, EBERs and EBNAs. EBNA1 binds a specific DNA sequence in the viral genome responsible for episome replication, segregation and persistence of the viral genome, and is involved in p53 degradation and oncogenesis. It is also involved in p53 degradation and oncogenesis. Since EBV infection is associated with the progression of malignancy in lymphoma, we used EBNA1-based PCR to determine the frequency of EBV infection in lymphoma specimens from patients with different types of lymphomas. Biopsies from lymphoma patients obtained from National Cancer Institute, Misurata and Tripoli Medical Centre (Libya) showed the presence of EBV in 31 of 40 cases (77%). EBV infection rates did not differ significantly between Hodgkin's lymphoma, and non-Hodgkin's lymphoma. The rates did not vary significantly between the sexes or age groups.


Assuntos
Infecções por Vírus Epstein-Barr/diagnóstico , Antígenos Nucleares do Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Linfoma/patologia , Linfoma/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Pré-Escolar , Feminino , Herpesvirus Humano 4/isolamento & purificação , Doença de Hodgkin/patologia , Doença de Hodgkin/virologia , Humanos , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/virologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
19.
Asian Pac J Cancer Prev ; 21(1): 133-137, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31983175

RESUMO

INTRODUCTION: Breast cancer (BC) is the most common malignancy affecting females worldwide. Various risk factors play a role in the developing of BC. Infectious agents like viruses have been proposed for this cancer and Epstein-Barr virus (EBV) is a widely researched candidate virus. This study detects the presence of EBV-DNA in breast cancer patients. METHODS: The study was conducted on 59 formalin-fixed paraffin-embedded (FFPE) tissue blocks samples of women with breast carcinoma and 11 non-neoplastic breast controls. The DNA was extracted for all the samples. Then detection of EBNA1 EBV was done by polymerase chain reaction (PCR). RESULTS: EBV was detected in 6.7% (4/59) of patients while all breast control samples were negative. All patients with positive EBV-DNA were high tumor grades (II, and III). Also, they had a low level of educations. CONCLUSIONS: According to our findings, it can be suggested that EBV may have a potential role in breast cancer development. However, this study provides substantial but not conclusive evidence for the involvement of viruses in BC disease development. Therefore, future investigations are needed to elucidate the exact role of EBV in breast cancer.
.


Assuntos
Neoplasias da Mama/epidemiologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Lobular/epidemiologia , Infecções por Vírus Epstein-Barr/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/virologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/virologia , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/virologia , DNA Viral/análise , DNA Viral/genética , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Irã (Geográfico)/epidemiologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Prevalência , Prognóstico
20.
Int J Cancer ; 146(8): 2089-2103, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31254479

RESUMO

We estimate the fractions of cancer attributed to infections in Africa in 2018. The number of new cancer cases occurring was taken from Globocan2018 with some additional estimations based on data from African population-based registries. Population attributable fractions were calculated using prevalence of infection and relative risk in exposed vs. nonexposed. The greatest share of infection-associated cancers is due to the human papillomaviruses (12.1% of all cancers in Africa and 15.4% in sub-Saharan Africa [SSA]); of these, cervical cancer is by far the most common. Kaposi sarcoma-associated herpesvirus is responsible for 3.1% of all cancers in Africa, the hepatitis viruses (B and C) for 2.9% and Helicobacter pylori for 2.7% (non-Cardia Gastric cancer and primary gastric lymphomas). Two percent of cancers are attributable to the Epstein-Barr virus, Schistosoma haematobium increases the risk of bladder cancer resulting in 1.0% of all cancers. HIV-related NHL and squamous cell carcinoma of the conjunctiva account for 0.6% of cancers. Altogether 24.5% of cancers in Africa and 28.7% in SSA are due to infectious agents. Infections are by far the most common cancer risk factor for cancer in Africa-the traditional risk factors (smoking, alcohol and unhealthy diet) probably cause only one in eight cancers in Africa. Prevention should focus on those infectious diseases preventable through vaccination (HPV and hepatitis B) which could reduce two-thirds of the burden. Helicobacter pylori and schistosomiasis are treatable with antibiotics and praziquantel, with a potential reduction of one in eight infection-associated cancers.


Assuntos
Infecções/epidemiologia , Neoplasias/epidemiologia , Neoplasias/microbiologia , Adolescente , Adulto , África/epidemiologia , Fatores Etários , Idoso , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/patologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/patologia , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/patologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Hepatite A/epidemiologia , Hepatite A/patologia , Hepatite B/epidemiologia , Hepatite B/patologia , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/patologia , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 8/isolamento & purificação , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Incidência , Infecções/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Fatores Sexuais , Adulto Jovem
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