Sarcoma de Kaposi ganglionar postrasplante renal: reporte de dos casos en un centro de trasplante colombiano Kaposi sarcoma in lymph nodes after kidney transplantation: report of two cases in a Colombian transplant center / Sarcoma de Kaposi ganglionar postrasplante renal: reporte de dos casos en un centro de trasplante colombiano Kaposi sarcoma in lymph nodes after kidney transplantation: report of two cases in a Colombian transplant center

El cáncer es una causa importante de morbilidad y mortalidad en los receptores de trasplante. La combinación de infecciones virales, terapia de inmunosupresión y la alteración en el sistema inmune en los pacientes trasplantados, contribuyen al desarrollo de cáncer. El sarcoma de Kaposi es causado por el virus herpes humano 8 (VHH-8), y aunque es raro en la población general, puede ser hasta 300 veces más frecuente en los pacientes con trasplante renal. El diagnóstico de la enfermedad se realiza a menudo con base en las características de las lesiones, pero debe ser confirmado por histología. En años recientes, los inhibidores de mTOR han mostrado ser efectivos para el control del sarcoma de Kaposi en los pacientes trasplantados, ya que se interrumpe el efecto antiapoptótico y la angiogénesis dependientes de la proteína mTOR, los cuales son esenciales para el desarrollo y la propagación de células malignas. Se presentan dos casos de pacientes con sarcoma de Kaposi ganglionar, sin lesiones en piel, en nuestro centro de trasplante, quienes respondieron de manera positiva al cambio del esquema inmunosupresor con inhibidores de mTOR

Cancer is a major cause of morbidity and mortality in transplant recipients. The combination of viral infections, immunosuppression therapy and immune system dysfunction in transplant patients contribute to the development of cancer. Kaposi sarcoma is caused by human herpes virus 8 (HHV-8) and although rare in the general population, it is reported to be up to 300 times more common in kidney transplant patients. Diagnosis of the disease is often made on the basis of the characteristic appearance of lesions, but must be confirmed by histology. In recent years, mTOR inhibitors have been shown to be effective in controlling Kaposi sarcoma in transplant patients, due to disruption of the antiapoptotic effect and angiogenesis dependent on the mTOR protein, which are essential for development and propagation of malignant cells. We present two case reports of patients with Kaposi sarcoma in lymph nodes and no skin lesions, who responded well to the immunosuppressive therapy switch with mTOR inhibitors

Sarcoma de Kaposi epidémico en África Subsahariana / Epidemic Kaposi sarcoma in Sub-Saharan Africa

El sarcoma de Kaposi se ha convertido en uno de los tumores más prevalentes en África tras la epidemia de VIH, que afecta de una manera similar a hombres y mujeres. El retraso diagnóstico y el limitado acceso a tratamiento antirretroviral o quimioterapia condicionan el pronóstico de los pacientes que lo padecen. En este artículo se realiza una revisión sobre la referida enfermedad, con el objetivo de describir sus aspectos más relevantes en los últimos años en África, como son su epidemiología, caractéristicas clínicas y opciones terapéuticas existentes. Este tumor es provocado por la infección por virus herpes humano tipo 8, que resulta más prevalente en las zonas rurales del continente africano. Se postula la transmisión a través de la saliva como la vía más importante de contagio en África. La inmunodepresión que causa el VIH favorece el efecto oncogénico del virus. La forma epidémica de SK se manifiesta inicialmente como lesiones hiperpigmentadas o violáceas en la piel, que pueden extenderse a linfáticos o mucosas y a nivel sistémico, principalmente a pulmón o aparato digestivo. El síndrome de reconstitución inmune sistémica puede complicar la evolución del paciente. El inicio temprano de la terapia antirretroviral resulta imprescindible. Además, el pronóstico de los pacientes mejora con la suma de tratamiento quimioterápico con doxorrubicina, vincristina, etopóxido o bleomicina principalmente(AU)

Kaposi sarcoma (KS) has become one of the most prevalent tumors in Africa after the HIV epidemic. KS affects both men and women. Diagnostic delay and limited access to antiretroviral treatment or chemotherapy have an impact on the prognosis of KS patients. A review was conducted about KS with the purpose of describing its most outstanding characteristics in recent years in Africa, such as its epidemiology, clinical features, and existing therapeutic options. This tumor is caused by infection with human herpesvirus 8, which is more prevalent in rural areas of the African continent. Transmission via saliva was found to be the most important transmission route in Africa. HIV-related immunosuppression fosters the oncogenic effect of the virus. The epidemic form of KS initially presents as hyperpigmented or violet-colored skin lesions which may extend to lymph nodes or mucosae, or systemically, mainly to the lungs or the digestive tract. Systemic immune reconstitution syndrome may complicate the patient's evolution. Early start of antiretroviral therapy is indispensable. Additionally, prognosis improves with chemotherapy with doxorubicin, vincristine, etoposide or bleomycin, mainly(AU)

HIV-associated lymphoma: A 5-year clinicopathologic study from India

Context: Relative risk of non-Hodgkin lymphoma (NHL) in people living with HIV is 60–200 times that of normal population. This is the largest series from India on lymphomas arising in HIV-infected individuals including workup for Epstein–Barr virus (EBV) and human herpesvirus-8 (HHV-8). Aims: This study aims to ascertain the distribution and detailed clinicopathologic features of lymphoma arising in HIV-infected persons in India. Settings and Design: The study was done during the period of 2007–2011 in the pathology department of a tertiary care center in South India. Subjects and Methods: All cases diagnosed as lymphoma in the department of pathology during the study period were identified, and patients with HIV positive by serology were included in the study. Clinical details were obtained from electronic records, slides were reviewed and tissue blocks retrieved, and immunohistochemistry for HHV-8 and in situ hybridization for EBV-encoded RNA was done. Statistical Analysis Used: Descriptive statistics were done using SPSS software. Kaplan–Meier curves were used to do survival analysis. Results: Of 3346 patients diagnosed with lymphoma, 73 (2%) were diagnosed to be positive for HIV. About 87.6% of the cases were NHL, of which diffuse large B-cell lymphoma was the most common and plasmablastic lymphoma was the second common subtype. Survival was uniformly poor in 36% of the cases where follow-up was available. Conclusions: The striking differences from world literature included higher frequency of plasmablastic lymphomas, lack of primary central nervous system lymphomas, and low association with HHV8.

Body Cavity–Based Lymphoma in a Country with Low Human Immunodeficiency Virus Prevalence: A Series of 17 Cases from the Consortium for Improving Survival of Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Primary effusion lymphoma (PEL) is a type of body cavity–based lymphoma (BCBL). Most patients with PEL are severely immunocompromised and seropositive for human immunodeficiency virus (HIV). We investigated the distinctive clinicopathologic characteristics of BCBL in a country with low HIV burden. MATERIALS AND METHODS: We retrospectively collected data on the clinicopathologic characteristics, treatments, and outcomes of 17 consecutive patients with BCBL at nine institutions in Korea. RESULTS: Latency-associated nuclear antigen 1 (LANA1) immunostaining indicated that six patients had PEL, six patients had human herpesvirus 8 (HHV8)-unrelated BCBL, and five patients had HHV8-unknown BCBL. The patients with PEL exhibited no evidence of immunodeficiency except for one who was HIV positive. One (20%) and four (80%) patients with PEL and six (100%) and zero (0%) patients with HHV8-unrelated BCBL were positive for CD20 and CD30 expression, respectively. The two patients with PEL (one HIV-positive and one HIV-negative patient) with the lowest proliferation activity as assessed by the Ki-67 labeling index survived for > 1 and > 4 years without chemotherapy, respectively, in contrast to the PEL cases in the literature, which mostly showed a high proliferation index and poor survival. CONCLUSION: PEL mostly occurred in ostensibly immunocompetent individuals and had a favorable outcome in Korea. A watchful waiting approach may be applicable for managing HIV-seronegative patients with PEL with a low Ki-67 labeling index. A possible trend was detected among LANA1, CD20, and CD30 expression in BCBL.

Kaposi's sarcoma in persons living with HIV/AIDS: a case series in a tertiary referral hospital

Abstract: Background: Kaposi's sarcoma (KS) is a rare neoplasm with indolent progression. Since 1981, the Kaposi's sarcoma epidemic has increased as co-infection with HIV. Objectives: The study aimed to identify the clinical and demographic characteristics and therapeutic approaches in HIV/AIDS patients in a regional referral hospital. Methods: We analyzed the medical records of 51 patients with histopathological diagnosis of Kaposi's sarcoma hospitalized at Hospital Universitário João de Barros Barreto (HUJBB) from 2004 to 2015. Results: The study sample consisted of individuals 15 to 44 years of age (80.4%), male (80.4%), single (86.3%), and residing in Greater Metropolitan Belém, Pará State, Brazil. The primary skin lesions identified at diagnosis were violaceous macules (45%) and violaceous papules (25%). Visceral involvement was seen in 62.7%, mainly affecting the stomach (75%). The most frequent treatment regimen was 2 NRTI + NNRTI, and 60.8% were referred to chemotherapy. Study limitations: We assumed that more patients had been admitted to hospital without histopathological confirmation or with pathology reports from other services, so that the current study probably underestimated the number of KS cases. Conclusion: Although the cutaneous manifestations in most of these patients were non-exuberant skin lesions like macules and papules, many already showed visceral involvement. Meticulous screening of these patients is thus mandatory, even if the skin lesions are subtle and localized.

Human Herpesvirus 8–Unrelated Primary Effusion Lymphoma–Like Lymphoma in an Elderly Korean Patient with a Good Response to Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone / Journal of the Korean Cancer Association, 대한암학회지

Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin’s lymphoma arising from a B-cell lineage characterized by the formation of malignant effusion in body cavities without evidence of a detectable tumor. The effusion contains tumor cells universally infected with human herpesvirus 8 (HHV8), which is the critical factor differentiating PEL from HHV8-unrelated PEL-like lymphoma (PEL-LL). This report describes a 77-year-old male patient with pleural effusion and ascites, containing lymphoma cells expressing a B-cell phenotype, but without markers of HHV8 in immunocytochemical analysis. The patient was diagnosed with PEL-LL and treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), which resulted in a complete remission. The patient is currently disease-free 15 months post-treatment. To the best of our knowledge, this is the first report on administration of R-CHOP in a PEL-LL patient in South Korea.

Human Herpesvirus 8-Negative and Epstein-Barr Virus-Positive Effusion-Based Lymphoma in a Patient with Human Immunodeficiency Virus

A 39-year-old man infected with human immunodeficiency virus (HIV) was admitted to our hospital because of sudden onset of chest pain. Chest radiography revealed pneumothorax of the right lung. Computed tomographic scans disclosed a 5.8-cm-sized emphysematous bulla in the right middle lobe of the lung. Histologically, the wedge-resected lung showed medium to large atypical cells within the bullous cavity of the Pneumocystis jirovecii pneumonia, without solid mass formation. These atypical cells were confirmed to be large B-cell lymphoma, Epstein-Barr virus-positive and human herpesvirus 8-negative. Therefore, this case was not diagnosed as primary effusion lymphoma, but effusion-based lymphoma arising in an emphysematous cavity of an HIV-infected patient. This type of effusion-based lymphoma has never been reported, and, although rare, it should be noted in order to clinically diagnose this lymphoma.

Células dendríticas plasmocitóides, expressão de receptores "Toll-like" 9 e 3 e de podoplanina nas lesões cutâneas do Sarcoma de Kaposi associado à síndrome de imunodeficiência adquirida e esporádico / Plasmacytoid dendritic cells and the expression of toll-like receptors 9 and 3 and podoplaninin in cutaneous lesions of Aids-associated Kaposi's sarcoma and classic Kaposi's sarcoma

INTRODUÇÃO: O Sarcoma de Kaposi (SK) é a neoplasia mais frequente dos doentes com Aids. É causada pelo herpes-vírus 8 (HHV-8). As células dendríticas plasmocitóides (CDp) são especializadas na produção de interferon tipo 1 e participam da resposta imune aos vírus. Os receptores "toll-like" são os principais receptores de reconhecimento de padrão, sendo que os receptores toll-like (TLR) 3 e 9 têm função no reconhecimento de vírus. O D2-40 é o anticorpo que reconhece a podoplanina, uma proteína transmembrana, presente no endotélio linfático e que tem função na imunidade. OBJETIVO: Demonstrar e comparar os componentes da imunidade inata: CDp e TLR 3 e 9, nas lesões cutâneas de SK associado a Aids e esporádico. Identificar a presença do HHV-8 nas CDp. Verificar o componente endotelial linfático na progressão das lesões de SK e comparar a expressão dos elementos da imunidade inata estudados, nas lesões com menor e maior componente endotelial linfático. MÉTODOS: Estudo retrospectivo de 50 biopsias de pacientes com diagnóstico de SK, todos com comprovação pelo exame histopatológico e demonstração do antígeno nuclear associado à latência (LANA) do HHV-8. Foram avaliados 11 biopsias de SK da forma clássica (SKc), 22 lesões de doentes com Aids (SK-Aids) e de 17 de doentes com Aids submetidos a tratamento com terapia antirretroviral altamente eficaz (SK-Aids/HAART). Os espécimes foram submetidos a exame por técnica imuno-histoquímica para evidenciar a presença de CDp (anticorpo CD303/BDCA-2), a expressão de TLR 3 e 9, bem como de podoplanina (anticorpo D2-40). Foi realizada também técnica de dupla marcação com CD303 e LANA, objetivando a identificação de CDp infectadas pelo HHV-8.Vinte e três espécimes de granuloma piogênico constituíram o grupo controle. A população de CDp e expressão de TLR 3 e TLR 9 também foi comparada nas lesões cutâneas de SK de doentes com e sem comprometimento visceral pela neoplasia; lesões não tumorais (máculo-papulares/placas)...

Introduction: Kaposi's sarcoma (KS) is the most common Aids-associated malignancy. It is caused by human herpesvirus-8. Plasmacytoid dendritic cells (pDC) are professional interferon producing cells, and participate in the immune response against viruses. Toll-like receptors (TLR) are the main pattern recognition receptors, and TLR 3 and TLR 9 participate in the recognition of viruses. Podoplanin, recognized by antibody D2-40, is a transmembrane protein identified on lymphatic endothelial cells with functions inimmunity. Objective: Demonstrate and compare some innate immunity components: pDC, TLR 3 and TLR 9, in cutaneous lesions of Aids-associated Kaposi's sarcoma and classic Kaposi's sarcoma. Identify the infection of pDC by HHV-8. Compare the lymphatic endothelial component in the course of tumor progression and compare the expression of innate immunity elements in lesions with a predominance of lymphatic endothelial components or not. Methods: Retrospective study of 50 biopsies diagnosed as Kaposi's sarcoma withpositive staining for latency-associated nuclear antigen (LANA) of HHV-8. Eleven classic KS, 22 Aids-associated KS and 17 Aids-associated KS from patients undergoing highly active antiretroviral therapy (HAART) were assessed. Paraffinembedded tissue was submitted to immunohistochemistry technique in order to demonstrate pDC (CD303/BDCA-2 antibody), expression of TLR 3, TLR 9 and podoplanin (D2-40 antibody). We performed double staining with CD303 and LANA in order to identify pDC infection with HHV-8. Twenty-three pyogenic granuloma(PG) specimens were analyzed as a control group. Plasmacytoid dendritic cells population, TLR 3 and TLR 9 expressions were compared between patients with and without visceral disease, nodular stageandpatch/plaque stage and according to bloodlymphocytes T CD4 count(< and >=350 cells/mm3)...

Sarcoma de Kaposi por virus del herpes humano de tipo 8 en un receptor de trasplante hepático pediátrico: Caso clínico / Human herpesvirus 8 related Kaposi's sarcoma in a pediatric liver transplant recipient: Case report

Los pacientes que reciben tratamiento inmunosupresor están en riesgo de desarrollar tumores malignos. La infección primaria o reactivación del virus del herpes humano de tipo 8 (HHV-8) puede predisponer al sarcoma de Kaposi después del trasplante de un órgano sólido. En los receptores de trasplantes pediátricos, este sarcoma tiene baja incidencia y mal pronóstico. Se informa la presentación clínica de un sarcoma de Kaposi en un ganglio linfático luego de una infección por HHV-8 en un niño a los 4 meses del trasplante hepático. El paciente tuvo buena evolución con suspensión del tacrolimus y conversión a sirolimus un mes después del diagnóstico. En nuestro conocimiento, este es el primer caso de sarcoma de Kaposi en un receptor pediátrico de trasplante hepático informado en nuestro país y creemos que esta entidad debería considerarse como diagnóstico diferencial en las complicaciones postrasplante.

Patients under immunosuppressive treatment are at risk of developing malignant tumors. Primary infection or reactivation of human herpesvirus 8 (HHV-8) may predispose to Kaposi's sarcoma (KS) after solid organ transplantation. KS in pediatric liver transplant recipients has low incidence and poor prognosis. We report the clinical presentation of a KS in lymph node following HHV-8 infection in a pediatric patient presenting four months after liver transplantation. He had a good outcome with suspension of tacrolimus and conversion to sirolimus one month after diagnosis. To our knowledge, this is the frst KS reported case in our country after liver transplant in a pediatric recipient and we believe that this entity should be taken into consideration in the differential diagnosis of post-transplant complications.

Kaposi Sarcoma in a Patient with Chronic Renal Failure Undergoing Dialysis

Kaposi sarcoma (KS) is a multicentric proliferative vascular tumor involving the skin and other organs. Human herpesvirus 8 (HHV-8) has been detected in KS lesions and is considered the putative causative agent of KS. The relationship between chronic renal failure, HHV-8, and KS is not clear. KS appears to develop in association with renal transplantation, but is unlikely with dialysis, and there have been few reports on this. Here, we report the case of a 51-year-old man, who underwent peritoneal dialysis to treat chronic renal failure, and presented with multiple brownish plaques on his soles. On histopathological examination, abnormally proliferated vessels, vascular slits, and spindle-shaped cells were seen in the dermis. Immunohistochemical staining for HHV-8 was positive. This case is another example in which factors other than immunosuppression contributed to the development of KS, due to activation of HHV-8.

Asociación del virus herpes humano 8 y la hiperplasia linfoide nodular difusa del intestino delgado en la inmunodeficiencia variable común / Association between the human herpesvirus 8 and the diffuse nodular lymphoid hyperplasia of the small intestine in common variable immunodeficiency

La inmunodeficiencia variable común (IDVC) es la inmunodeficiencia primaria más frecuente en el terreno clínico y sus formas de presentación son muy variables. Se describe una paciente con IDVC de adulto con síndrome diarreico crónico, pérdida de peso y linfoadenopatías difusas. Sus características inmunológicas más notables fueron una profunda hipogammaglobulinemia de las 3 clases mayores de inmunoglobulinas y la disminución numérica de las células B (CD19+) y células NK (CD3-CD56+) en sangre periférica. La biopsia del intestino delgado obtenida por panendoscopia asistida por video, reveló hiperplasia linfoide multinodular con atrofia parcial de las vellosidades. La inmunohistoquímica mostró que los nódulos consistían en centros germinales aumentados de tamaño con una distribución de células B (CD20+) y células T (CD3+), similar a la del folículo normal. No se encontró expresión diferencial de cadenas ligeras κ y λ. El método de la reacción en cadena de la polimerasa en tiempo real (QRT-PCR) detectó un número apreciable de copias del genoma del virus del herpes humano tipo 8 (VHH-8) (133 copias/µL de ADN) en el ADN del nódulo intestinal biopsiado. La infección con el VHH-8 puede ser un factor importante en la patogenia de los trastornos linfoproliferativos en pacientes con IDVC.

The common variable immunodeficiency (CVID) is the more frequent primary immunodeficiency in clinical field and its presentation forms are very variable. We describe the case of a women presenting with adult CVID with chronic diarrhea syndrome, weight loss and diffuse lymphadenopathies, where the more marked immunologic features were a deep hypogammaglobulinemia of the three major kinds of immunoglobulins and numerical decrease of B cells (CD19+) and NK cells (CD3-CD56+) in peripheral blood. Biopsy of small intestine obtained by video-assisted panendoscope, showed the presence of a multinodular lymphoid hyperplasia with partial atrophy of hairinesses. Immunohistochemistry showed that nodules were high germinal centers with distribution of B cells (CD20+) and T cells (CD3+), similar to that of normal follicle. There was not differential expression of the K and λ light chains. The real time polymerase chain reaction (QRT-PCR) method detected many copies from the genome of type 8 human herpesvirus (VHH-8) (133 copies/µL of DNA) in biopsy of intestinal nodule DNA. VHH-8 infection may to be a significant factor in pathogenesis of lymphoproliferative disorders in patients presenting with CVID.

First survey for detecting the presence of human herpesvirus 8 infection (HHV-8) in Maputo, Mozambique

Human herpesvirus 8 (HHV-8), the etiological agent of Kaposi's sarcoma (KS), is endemic in parts of the sub-Saharan, and KS has increased concomitantly with the HIV/AIDS epidemic. In Mozambique (MZ), no data concerning HHV-8 infection was available, thus the main of this work was to investigate, for the first time, the presence of HHV-8 infection in Maputo, MZ. Latent and lytic HHV-8-specific antibodies were assessed in blood samples from 189 individuals from the Central Hospital of Maputo, MZ, using "in-house" immunofluorescence assays conducted in São Paulo, Brazil. The results obtained were analyzed according to socio-demographic and clinical variables using the Chi-square test and logistic regression. An HHV-8 seropositivity of 1.8 percent and 9.7 percent was detected among 57 medical students and 31 individuals from the staff, respectively, in contrast to 16.4 percent detected among 67 out-patients. Concerning 34 hospitalized patients from the Dermatology Unit, 47.1 percent were HHV-8-seropositive overall, while the rate was 85.7 percent among KS patients. The present survey, conducted in Maputo, MZ, demonstrates great variation in HHV-8 infection frequencies depending on the group analyzed and epidemiological variables. An association between HHV-8 seropositivity and male gender (OR 5.72), the central origin of patients (OR 5.33), blood transfusions (OR 3.25), and KS (OR 24.0) was detected among hospitalized patients, and primary school (OR 7.18) and HIV-1 infection (OR 8.76) among out-patients.

Estudo epidemiológico da infecção por herpesvírus 8 humano (HHV-8) em população indígena da Amazônia brasileira / Epidemiological study of human herpesvirus 8 infection (HHV-8) in the amerindian population from Brazilian Amazon

O Herpesvírus 8 humano (HHV-8) é endêmico em populações africanas e indígenas da região Amazônica. A infecção nestas populações acontece durante a infância e, na África, envolve o contato íntimo no ambiente intrafamiliar. Diversos estudos confirmam a distribuição geográfica dos diferentes subtipos de HHV-8, sendo que o subtipo E é típico das populações indígenas. Objetivos: 1. Caracterizar o(s) subtipo(s) de HHV-8 que circula(m) em população indígena da Amazônia brasileira baseado na análise da região ORF K1 do vírus; 2. Construir a árvore filogenética dos subtipos virais encontrados; 3. Comparar filogeneticamente os subtipos encontrados com os subtipos prevalentes em outras populações indígenas do Brasil e de outros países da América do Sul; 4. Calcular a taxa de substituição para a região VR1 do HHV-8 para as amostras estudadas; 5. Estimar a data de entrada do vírus na população do estudo; 6. Investigar a dinâmica de transmissão do vírus no ambiente intrafamiliar; 7. Averiguar se há correlação entre os alelos de HLA classe I (A e B) e II (DQB1 e DRB1) e suscetibilidade à infecção por HHV-8. Casuística e métodos: Estudo de soroprevalência da infecção por HHV-8 em amostra de população indígena da Amazônia brasileira utilizando IFI para detecção de antígenos da fase latente (LANA) e lítica (Lítico) do vírus. Análise filogenética da amostras encontradas utilizando-se o DNA/HHV-8 extraído de amostras de saliva, submetidas à reação de nested PCR para amplificar as regiões hipervariáveis VR1 e VR2. Cálculo da taxa de substituição do HHV-8, utilizando-se os métodos de distância e técnica bayesiana. Estimar a data do ancestral comum mais recente para as amostras em estudo, utilizando-se o programa BEAST. Tipagem de HLA de indivíduos positivos e negativos para a infecção por HHV-8, utilizando-se a técnica de PCR-SSO. Resultados: A soroprevalência geral da infecção por HHV-8 na população em estudo foi de 75,3% (399/530). Observou-se que a soropositividade...

The human herpesvirus 8 (HHV-8) is endemic in Africa and Amerindian populations from Amazon region. The infection in those populations occurs during childhood and, in Africa, involves a close contact in intrafamilial environment. Several studies confirm the geographical distribution of different subtypes of HHV-8, and the subtype E is typical of the Amerindian population. Objectives: 1. To characterize the HHV-8 subtypes circulating in Amerindian population from Brazilian Amazon, based on the analysis of ORF K1 region of the virus. 2. To construct a phylogenetic tree of viral subtypes found among Amerindians 3. To compare by phylogenetic methods the subtypes found in Mapuera Amerindians with the subtypes prevalent in others Amerindians populations of Brazil and South America 4. To determine the substitution rate of VR1 region of HHV-8 for the sequences obtained in the present study 5. To estimate the date of entry of the viruses in the Mapuera population 6. To investigate the dynamic of transmission of the virus in the intrafamilial environment 7. To investigate if there is a correlation between susceptibility to HHV-8-infection and HLA class I (A and B) and II (DQB1 and DRB1) alleles. Patients and methods: The seroprevalence of HHV-8 infection in a sample of the indigenous population of the Brazilian Amazon was carried out using IFA to detect antibodies to latent (LANA) and lytic phase antigens of HHV-8. Phylogenetic analysis of the sequences was performed by using the DNA extracted from samples of saliva, using a nested PCR to amplify the hypervariable regions VR1/ VR2 of HHV-8. Estimation of the substitution rate of HHV-8 nucleotides was performed by using the method of distance and the Bayesian technique. Estimates of the time of the most recent common ancestor (TMRCA) for all samples studied were done by using the BEAST program. HLA typing of positive and negative subjects for HHV-8 infection was performed by using the PCR-SSO technique...

Relationship between open reading frame 26 subtypes in human herpesvirns-8 and Kaposi's sarcoma / 中华皮肤科杂志

Objective To learn the subtypes of open reading frame 26 (ORF26) of human herpesvirus 8 (HHV-8) in patients with Kaposi's sarcoma, and to evaluate the relationship of ORF26 subtypes to clinical types and invasiveness of Kaposi's sarcoma. Methods Thirty-two paraffin-embeded tissue speci-mens of Kaposi's sarcoma were collected in the Department of Dermatology, People's Hospital of Xinjiang Uygur Autonomous Region, from 1996 to 2007. DNA was extracted from these specimens, nested-PCR was used to amplify HHV-8 DNA. PCR products were subjected to bi-directional sequencing after extraction from agarose gels. Phylogenetic analysis was carded out by using the software DNAStar, program Clustal W and PHYLIP package for the determination of ORF26 subtype. Fisher's exact test was performed to evaluate the relationship of ORF26 subtypes to clinical types and invasiveness of Kaposi's sarcoma. Results Of the 32 specimens, 30 were positive for HHV-8 DNA with a positivity rate of 93.75%, and 6 specimens of AIDS related Kaposi's sarcoma were all positive. ORF26 A subtype was detected in the HHV-8 DNA of 17 posi-tive specimens, and C subtype in that of other 13 specimens. Neither the incidence of mucosal lesions nor the distribution of clinical subtypes was of significant difference between patients with ORF26 A subtype and those with ORF26 C subtype (both P > 0.05). Conclusions A and C may be the predominate subtypes of ORF 26 in HHV-8 of patients with Kaposi's sarcoma, and the ORF26 subtype is unrelated to the presence of mucosal lesions in or the clinical types of patients with Kaposi's sarcoma.

Multi-transmembrane protein K15 of Kaposi's sarcoma-associated herpesvirus targets Lyn kinase in the membrane raft and induces NFAT/AP1 activities

Viral proteins of gamma-2 herpesviruses, such as LMP2A of Epstein Barr virus (EBV) and Tip of herpesvirus saimiri (HVS) dysregulate lymphocyte signaling by interacting with Src family kinases. K15 open reading frame of Kaposi's sarcoma associated herpesvirus (KSHV), located at the right end of the viral genome, encodes several splicing variants differing in numbers of transmembrane domains. Previously, we demonstrated that the cytoplasmic tail of the K15 protein interfered with B cell receptor signal transduction to cellular tyrosine phosphorylation and calcium mobilization. However, the detailed mechanism underlying this phenomenon was not understood. In the C-terminal cytoplasmic region of K15, putative binding domains for Src-SH2 and -SH3 were identified. In this study, we attempted to characterize these modular elements and cellular binding protein(s) by GST pull down and co-immunoprecipitation assays. These studies revealed that K15 interacted with the major B cell tyrosine kinase Lyn. In vitro kinase and transient co-expression assays showed that the expression of K15 protein resulted in activation of Lyn kinase activity. In addition, GST pull down assay suggested that the SH2 domain of Lyn alone was necessary for interaction with the C-terminal SH2B (YEEV) of K15, but the addition of Lyn SH3 to the SH2 domain increases the binding affinity to K15 protein. The data from luciferase assays indicate that K15 expression in BJAB cells induced NFAT and AP1 activities. The tyrosine residue in the C-terminal end of K15 required for the Lyn interaction appeared to be essential for NFAT/AP1 activation, highlighting the significance of the C-terminal SH2B of K15 as a modular element in interfering with B lymphocyte signaling through interaction with Lyn kinase.

Progress on the Study of Human Herpesvirus-8 / 中国生物工程杂志

Human herpesvirus-8 (HHV-8) also referred to as Kaposi’s sarcoma-associated herpes-virus (KSHV),is a novel tumor causing virus,which is thought to be the etiologic agent of KS,and also is associated with primary effusion lymphoma(PEL) and multicentric castleman’s disease(MCD) HHV-8 encodes a number of viral proteins, including the proteins associated with HHV-8 latent infection and lytic infection,and the proteins unique to HHV-8,which are critical players in the development of KS and HHV-8-associated diseases. The proteins encoded by HHV-8 and association between HHV-8 and KS were reviewed.

A Case of Kaposi's Sarcoma Associated with Castleman's Disease / 대한피부과학회지

Castleman's disease, also known as angiofollicular lymphoid hyperplasia or giant lymph-node hyperplasia, is an unusual form of a lymphoproliferative disorder, and is divided clinically into a solitary and a multicentric form. The multicentric form of Castleman's disease is almost always of the plasma cell type. This can coexist with Kaposi's sarcoma in some cases. Kaposi's sarcoma is a multicentric, proliferative, vascular tumor involving cutaneous and visceral tissue. Iatrogenically-developed, immunosuppression-associated Kaposi's sarcoma is usually the result of immunosuppressive therapy. A 61-year-old man diagnosed as the plasma cell type of Castleman's disease, who had been treated with prednisolone for 2 years, was referred to the department of dermatology with numerous skin lesions consisting of confluent, violaceous-colored papules and plaques on his palm and soles. Histologic examination of the cutaneous lesions showed consistency with Kaposi's sarcoma. We report a rare case of Kaposi's sarcoma associated with multicentric Castleman's disease.

Questionable Role of Human Herpesvirus-8 in the Pathogenesis of Multiple Myeloma

BACKGROUND: Human herpesvirus 8 (HHV-8) has been strongly implicated in the etiopathogenesis of multiple myeloma. Cytokines, especially interleukin-6, that are produced by HHV-8 infected bone marrow stromal cells may play a role in the proliferation of neoplastic plasma cells. Viral DNA sequences have been detected in the bone marrow and peripheral blood cells of myeloma patients. Yet some investigators have not found the same results. METHODS: We exmined the presence of HHV-8 DNA in the paraffin-embedded cell block specimens of bone marrow aspirations from 26 patients with multiple myeloma by polymerase chain reaction (PCR) with KS330(233) primers. Thirteen cases of bone marrow aspirations from patients with other diseases were used as a negative control. The DNA extracted from the BC-1 cell line was used as a positive control. Immunohistochemistry using commercially available HHV-8 antibody was done in the cases that were proven HHV-8 DNA-positive by PCR. RESULTS: One case (3.9%) among the 26 patients with myleoma was positive for HHV-8 DNA by PCR, but no positive cells were detected in this case by immunohistochemistry. CONCLUSIONS: We could not find a clear relation between myeloma and HHV-8 in Korean patients examined in the present study.

Three Cases of Primary Effusion Lymphoma / 대한혈액학회지

Primary effusion lymphoma (PEL) is a recently described rare type of non-Hodgkin's lymphoma which develops in serous body cavity without clinically identifiable tumor masses. Human herpesvirus (HHV)-8 was recognized to play a pathogenic role in the development of PEL in immunocompromised patients such as human immunodeficiency virus (HIV) positive patients or elderly. However, several cases of HHV-8 negative PEL have been reported. Here we describe a case of HHV-8 positive PEL with both of hepatocellular carcinoma and liver cirrhosis and two cases of HHV-8 negative PEL with liver cirrhosis and fatty liver each. Considering the reported and current HHV-8 negative PEL cases, we need to expand the concept of PEL.