Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

Acometimento pulmonar e articular secundário à síndrome de Lemierre: relato de caso e revisão de literatura / Pulmonary and joint involvement secondary to Lemierre syndrome: case report and literature review

A síndrome de Lemierre caracteriza-se por uma rara entidade que gera tromboflebite da veia jugular interna e embolismo séptico em história da infecção recente da orofaringe, além de sinais radiológicos e isolamento de patógenos anaeróbicos, principalmente Fusobacterium necrophorum. Relatamos o caso de uma paciente do sexo feminino, 13 anos de idade, com histórico de carcinoma de nasofaringe associado ao vírus Epstein-Barr (estadiamento T4N2M0), submetida a procedimentos cirúrgicos e quimiorradioterapia. Iniciou com queixa de mialgia intensa, diplopia, lesões infectadas em membros e choque séptico. Por meio de exames de ultrassonografia cervical com Doppler colorido e tomografia computadorizada de pescoço com contraste endovenoso, foram identificados trombos intraluminais na veia jugular interna, além de trombos sépticos pulmonares, por meio da tomografia computadorizada de tórax. Posteriormente, ainda evoluiu com artrite piogênica coxofemoral esquerda. Foi isolada, por hemocultura, a bactéria Klebsiella pneumoniae Carpemenase, e o tratamento se deu pela associação entre vancomicina, amicacina, meropenem, metronidazol e anfotericina B. Conclui-se que, após o diagnóstico de SL e, embora com múltiplas complicações e diagnóstico tardio, a paciente encontra-se bem e assintomática, além do relato comprovar a dificuldade diagnóstica e de seu tratamento

Lemierre's syndrome is a rare condition that leads to thrombophlebitis of the internal jugular vein and septic embolism following recent oropharyngeal infection, being characterized by radiological signs and isolation of anaerobic pathogens, especially Fusobacterium necrophorum. We report the case of a 13-year-old female patient with history of nasopharyngeal carcinoma associated with Epstein-Barr virus (T4N2M0 staging), who underwent surgical procedures and chemoradiotherapy. Her initial complaint was severe myalgia, diplopia, infected limb injuries, and septic shock. Cervical color Doppler ultrasound and computed tomography scan of the neck with intravenous contrast showed intraluminal thrombi in the internal jugular vein, and chest computed tomography showed pulmonary septic thrombi. Subsequently, she progressed with left coxofemoral pyogenic arthritis. The bacterium Klebsiella pneumoniae Carpemenase was isolated in blood culture, and the patient was treated with the association of vancomycin, amikacin, meropenem, metronidazole, and amphotericin B. It is concluded that, despite the multiple complications and late diagnosis, the patient is well and asymptomatic after the diagnosis of Lemierre's syndrome; in addition, the report proves the difficulty of diagnosis and treatme

Detecção de Epstein-Barr vírus no carcinoma da nasofaringe: implicações numa área de baixo risco / Epstein-Barr virus detection in nasopharyngeal carcinoma: implications in a low-risk area

Several studies have been published concerning Epstein-barr virus (EBV) infection and nasopharyngeal cancer (NPC) development. The incidences of histological types are different according to endemic or non-endemic regions. Latent EBV infection is found in almost all cases of NPC in endemic regions, but normally absent in type I carcinomas, more common in non-endemic regions. AIM: The purpose of this hospital-based study was to analyze the presence of EBV in nasopharyngeal tumor tissues and in peripheral blood of nasopharyngeal cancer patients and healthy individuals, in a low risk, non-endemic area. METHODS: EBV detection in samples of nasopharyngeal cancer patients and healthy individuals. RESULTS: This study indicates that the frequency of EBV positive cases in peripheral blood is higher in advanced tumor stages. CONCLUSIONS: The incidence rates of NPC have a distinct distribution. Since the prevalence of this disease is low in occidental countries, little is known about the biology of these tumors in non-endemic areas. We observed statistically significant differences in EBV detection between the NPC patient group and the control group. This study may help to understand the biological mechanisms of NPC and the correlation of EBV infection with this disease, in a low risk, non-endemic region.

Têm sido publicados vários estudos acerca da infecção por Epstein-Barr vírus (EBV) e o desenvolvimento de carcinoma da nasofaringe (NPC). As prevalências dos tipos histológicos e a presença de infecção latente pelo EBV são diferentes em regiões endémicas e não endémicas. OBJETIVO: O objectivo deste estudo consistiu na detecção de EBV em tecido tumoral da nasofaringe e sangue periférico de doentes com NPC e em indivíduos saudáveis, provenientes duma área não-endémica, de baixo risco. MÉTODOS: Detecção de EBV em amostras de doentes com carcinoma da nasofaringe e indivíduos saudáveis. Neste estudo de série foram avaliadas as implicações clínicas da presença de EBV circulante no sangue periférico de doentes com carcinoma da nasofaringe. RESULTADOS: Este estudo indica que a frequência de casos EBV positivos detectados no sangue periférico é superior em tumores de estádio mais avançado. CONCLUSÕES: Estes resultados indicam que se observam diferenças na pesquisa do vírus Epstein-Barr no grupo de doentes com NPC e no grupo controlo, sem tumor. Este estudo pode ajudar na compreensão dos mecanismos biológicos do cancro da nasofaringe e da correlação destes tumores com a infecção por EBV numa área não-endémica, de baixo risco.

Genetic variations of EBV-LMP1 from nasopharyngeal carcinoma biopsies: potential loss of T cell epitopes

To find Epstein-Barr virus (EBV) strains with genetic variations of EBV latent membrane protein 1 (EBV-LMP1) from nasopharyngeal carcinoma (NPC), the full-length DNA of LMP1 genes from 21 NPC biopsies obtained in Hunan province in southern China was amplified and sequenced. Our sequences were compared to those previously reported by the Clustal V method. Results showed that all 21 sequences displayed two amino acid changes most frequently in LMP1 of CD4+ T cell epitopes at codons 144 (F arrow right I, 21/21) and 212 (G arrow right S, 19/21) or (G arrow right N, 2/21). We also show that type A EBV strain is prevalent in the cases of NPC from Hunan province with a 30-bp 18/21 deletion, and we highlight that this deletion resulted in loss of one of the CD4+ T cell-restricted epitopes. The other 3 sequences without this deletion all had a change at codon 344 (G arrow right D). Furthermore, in the major epitope sequence of CD8+ T cells restricted by HLA-A2, all 21 sequences showed changes at codons 126 (L arrow right F) and 129 (M arrow right I). Our study discovered that one of the 21 sequence variations harbored a new change at codon 131 (W arrow right C), and 5/21 specimens showed another novel change at codon 115 (G arrow right A) in the major epitope sequence of CD8+ T cells restricted by HLA-A2. Our study suggests that these sequence variations of NPC-derived LMP1 may lead to a potential escape from host cell immune recognition, protecting latent EBV infection and causing an increase in tumorigenicity.

[Detection of EBV by PCR in fresh and paraffin-embedded naso pharyngeal carcinoma biopsies]

The nasopharyngeal carcinoma [NPC] is frequent in Tunisia. It's the second ORL cancer of men after the larynx one. To analyse the NPC characteristics in our population, we determined the frequency of EBV infection in 47 paraffin-embedded and 6 fresh NPC biopsies. We first extracted the DNA from tumoral tissus and then amplified viral sequences by PCR to detect and to type the infecting virus [EBV-A or ABV-B]. Our results showed that amplifiable DNA has been obtained from 34/47 paraffin-embedded NPC biopsies while 13/47 of the others biopsies contained degraded and not amplifiable DNA. All the fresh biopsies allowed to obtain DNA with good quality. The EBV infection frequency in paraffin-embedded NPC biopsies is 35% while EBV is detected in all fresh biopsies [6/6]. Our analyse also showed that the EBV-A is predominant in our population compared to EBV-B as it was shown in most countries of the world. This study clearly shows that PCR results obtained with paraffin-embedded NPC biopsies are divergeant from those obtained with fresh biopsies. Because of DNA degradation in paraffin-embedded NPC biopsies, the biology molecular results from that kind of samples is criticable. Moreover, the results obtained from fresh NPC biopsies confirmed the quasi-constant association of EBV with undifferenciated carcinoma nasopharyngeal type

Identificacion del virus Epstein-Barr en carcinomas nasofaringeos en Argentina: su relacion con P53 y determinacion de indices de proliferacion / Identification of Epstein-Barr virus in nasopharyngeal carcinomas in Argentina: its relation with p53 and the determination of proliferation indices

Se estudiaron 37 casos de carcinomas nasofaríngeos (CNF) a partir de biopsias de cavum incluidas en parafina. Los pacientes fueron argentinos, 23 hombres y 14 mujeres cuyo promedio de edad fue de 50 años. Los tumores se clasificaron en carcinoma escamoso queratinizante, 1 caso (2 por ciento), carcinomas escamosos no queratinizantes, 15 casos (41 por ciento) y carcinomas indiferenciados, 21 casos (57 por cento). Se determinó el índice de proliferación (PI) con anticuerpos monoclonales para PCNA y Ki-67 (MIB-1) que fue del 26 por ciento y 17 por ciento respectivamente, no hallándose aparentemente diferencias de acuerdo a las variantes histológicas, estadios clínicos III o IV de presentación. El IP fue del 2 por ciento para estadio II aunque los casos en la serie fueron escasos (n = 3). Se observó positividad para p53 en 30 de los 37 casos, similar para los carcinomas indiferenciados y no queratinizantes, mientras que el carcinoma queratinizante fue negativo. Se estabelecieron dos grupos de pacientes con sobrevida media de 35 y 12 meses a partir de un valor de corte en el porcentaje de positividad por inmunomarcación para p53 (< y > 7 por ciento), si bien la diferencia no fue estadísticamente significativa. Se demostró la presencia del virus Epstein-Barr por PCR en 31 de 37 de los CNF: 19 fueron caracinomas indiferenciados y 12 fueron carcinomas escamosos no queratinizantes, siendo negativo el carcinoma escamoso queratinizante. Estos resultados, obtenidos por primera vez en Argentina, son semejantes a los hallados en países con alta y baja frecuencia de CNF y pueden ser de valor para estabelecer el origen nasofaríngeo de una adenopatía cervical metastásica de origen desconocido.

Biologia molecular no diagnóstico das infecçöes por papilomavirus humano (HPV) em otorrinolaringologia / Molecular biology in the diagnosis of human papillomavirus (HPV) infection in otolaryngology

As técnicas de hibridizaçäo de DNA tem possibilitado tanto a detecçäo como a identificaçäo de diferentes tipos e subtipos de vírus envolvidos em várias afecçöes. Os autores fazem resisäo a respeito da utilizaçäo e resultados desta técnica en afecçöes da cavidade oral (Leucoplasia, Papiloma de Células Escamosas, Verruga Vulgar da cavidade oral, Hiperplasia Epitelial Focal, Ceratoacantoma); nasofaringe (Papilomas) e laringe (Câncer de Laringe, Papilomatese Recorrente do Trato Respiratório).