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      Human herpesvirus 8 (HHV-8) detected by nested polymerase chain reaction (PCR) in HIV patients with or without Kaposi’s sarcoma. An analytic cross-sectional study : Herpesvírus humano 8 (HHV-8) detectado por reação da polimerase em cadeia do tipo nested PCR em pacientes HIV-positivos com ou sem sarcoma de Kaposi. Um estudo transversal analítico

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          ABSTRACT

          CONTEXT AND OBJECTIVE:

          Kaposi’s sarcoma (KS) is a common neoplastic disease in AIDS patients. The aim of this study was to evaluate the frequency of human herpesvirus 8 (HHV-8) infection in human immunodeficiency virus (HIV)-infected patients, with or without KS manifestations and correlate HHV-8 detection with KS staging.

          DESIGN AND SETTING:

          Analytic cross-sectional study conducted in a public tertiary-level university hospital in Ribeirão Preto, São Paulo, Brazil.

          METHODS:

          Antibodies against HHV-8 lytic-phase antigens were detected by means of the immunofluorescence assay. HHV-8 DNA was detected in the patient samples through a nested polymerase chain reaction (nested PCR) that amplified a region of open reading frame (ORF)-26 of HHV-8.

          RESULTS:

          Anti-HHV-8 antibodies were detected in 30% of non-KS patients and 100% of patients with KS. Furthermore, the HHV-8 DNA detection rates observed in HIV-positive patients with KS were 42.8% in serum, 95.4% in blood samples and 100% in skin biopsies; and in patients without KS, the detection rate was 4% in serum. Out of the 16 serum samples from patients with KS-AIDS who were classified as stage II, two were positive (12.5%); and out of the 33 samples from patients in stage IV, 19 (57.6%) were positive.

          CONCLUSION:

          We observed an association between HHV-8 detection and disease staging, which was higher in the serum of patients in stage IV. This suggests that detection of HHV-8 DNA in serum could be very useful for clinical assessment of patients with KS and for monitoring disease progression.

          RESUMO

          CONTEXTO E OBJETIVO:

          Sarcoma de Kaposi (SK) é uma doença neoplásica comum em pacientes com aids. O objetivo deste estudo foi avaliar a frequência da infecção por herpesvírus humano 8 (HHV-8) em pacientes infectados por HIV, com ou sem SK e associar a detecção do HHV-8 com o estadiamento do SK.

          TIPO DE ESTUDO E LOCAL:

          Estudo transversal analítico realizado em hospital universitário público terciário de Ribeirão Preto, São Paulo, Brasil.

          MÉTODOS:

          Anticorpos contra antígenos de fase lítica do HHV-8 foram detectados por imunofluorescência. O DNA viral de HHV-8 foi detectado em amostras de pacientes pela reação em cadeia da polimerase do tipo nested ( nested PCR), que amplificou uma região do fragmento de leitura aberta (ORF)-26 do HHV-8.

          RESULTADOS:

          Anticorpos anti-HHV-8 foram detectados em 30% dos pacientes sem SK e 100% dos com SK. Além disso, a detecção de HHV-8 DNA observada em pacientes HIV-positivos com SK foi de 42,8% no soro, 95,4% em amostras de sangue e 100% em biópsias de pele, e em pacientes sem SK foi de 4% no soro. Das 16 amostras de soro de pacientes com SK-AIDS classificados como estádio II, duas foram positivas (12,5%) e, das 33 amostras de pacientes no estádio IV, 19 (57,6%) foram positivas.

          CONCLUSÃO:

          Observamos associação entre a detecção do HHV-8 e o estadiamento da doença, que foi maior no soro de pacientes no estágio IV. Isso sugere que a detecção do HHV-8 no soro poderia ser muito útil para a avaliação clínica de pacientes com SK e para o monitoramento da progressão da doença.

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          Most cited references94

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          Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma.

          Representational difference analysis was used to isolate unique sequences present in more than 90 percent of Kaposi's sarcoma (KS) tissues obtained from patients with acquired immunodeficiency syndrome (AIDS). These sequences were not present in tissue DNA from non-AIDS patients, but were present in 15 percent of non-KS tissue DNA samples from AIDS patients. The sequences are homologous to, but distinct from, capsid and tegument protein genes of the Gammaherpesvirinae, herpesvirus saimiri and Epstein-Barr virus. These KS-associated herpesvirus-like (KSHV) sequences appear to define a new human herpesvirus.
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            Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas.

            DNA fragments that appeared to belong to an unidentified human herpesvirus were recently found in more than 90 percent of Kaposi's sarcoma lesions associated with the acquired immunodeficiency syndrome (AIDS). These fragments were also found in 6 of 39 tissue samples without Kaposi's sarcoma, including 3 malignant lymphomas, from patients with AIDS, but not in samples from patients without AIDS. We examined the DNA of 193 lymphomas from 42 patients with AIDS and 151 patients who did not have AIDS. We searched the DNA for sequences of Kaposi's sarcoma-associated herpesvirus (KSHV) by Southern blot hybridization, the polymerase chain reaction (PCR), or both. The PCR products in the positive samples were sequences and compared with the KSHV sequences in Kaposi's sarcoma tissues from patients with AIDS. KSHV sequences were identified in eight lymphomas in patients infected with the human immunodeficiency virus. All eight, and only these eight, were body-cavity-based lymphomas--that is, they were characterized by pleural, pericardial, or peritoneal lymphomatous effusions. All eight lymphomas also contained the Epstein-Barr viral genome. KSHV sequences were not found in the other 185 lymphomas. KSHV sequences were 40 to 80 times more abundant in the body-cavity-based lymphomas than in the Kaposi's sarcoma lesions. A high degree of conservation of KSHV sequences in Kaposi's sarcoma and in the eight lymphomas suggests the presence of the same agent in both lesions. The recently discovered KSHV DNA sequences occur in an unusual subgroup of AIDS-related B-cell lymphomas, but not in any other lymphoid neoplasm studied thus far. Our finding strongly suggests that a novel herpesvirus has a pathogenic role in AIDS-related body-cavity-based lymphomas.
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              Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease.

              Multicentric Castleman's disease (MCD) is an atypical lymphoproliferative disorder defined using clinical and pathologic criteria. A characteristic of the MCD is a close association with Kaposi's sarcoma (KS), which occurs during the clinical course of most human immunodeficiency virus (HIV)-associated MCD cases and also, but less frequently, in HIV-negative patients. Recently, sequences of a putative new Herpesvirus (KSHV) have been isolated and further detected in almost all the acquired immunodeficiency syndrome (AIDS) KS and in most of the non-AIDS KS samples. In this study, we searched for these Herpesvirus-like sequences in MCD samples of 31 patients. KSHV sequences were detected in 14 of 14 cases of HIV-associated MCD, including 5 cases without detectable KS. Moreover, KSHV was detected in 7 of 17 MCD cases in HIV-negative patients, including 1 case associated with a cutaneous KS. In 34 non-MCD reactive lymph nodes (follicular and/or interfollicular hyperplasia) in HIV-negative patients, KSHV was detected in only 1 case. In 1 HIV-negative case of MCD, KSHV was found in both the lymph node and peripheral blood samples. These data suggest that KSHV could play a role in the pathogenesis of MCD, especially in HIV-infected patients.
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                Author and article information

                Journal
                Sao Paulo Med J
                Sao Paulo Med J
                Sao Paulo Med J
                São Paulo Medical Journal
                Associação Paulista de Medicina - APM
                1516-3180
                1806-9460
                14 April 2015
                2016
                : 134
                : 3
                : 187-192
                Affiliations
                [I ] originalPhD. Biomedical Scientist, Virology Research Center, Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
                [II ] originalMSc. Biologist, Virology Research Center, Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
                [III ] originalPhD. Veterinarian, Virology Research Center, Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
                [IV ] originalMD, PhD. Associate Professor, Virology Research Center, Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
                Author notes
                Address for correspondence: Paula Renata Lima Machado. Av. Bandeirantes, 3.900, Ribeirão Preto (SP) - Brasil. CEP 14049-900. Tel. (+55 16) 3602-3251. E-mail: paulamachado@ 123456usp.br

                Conflict of interest: None

                Article
                10.1590/1516-3180.2014.8973010
                10496606
                25885486
                56770580-aaad-40f5-8cf1-3ae7cd1d3b5c

                This is an open access article distributed under the terms of the Creative Commons license.

                History
                : 25 May 2014
                : 26 October 2014
                : 30 October 2014
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 33, Pages: 06
                Categories
                Original Article

                sarcoma, kaposi,herpesvirus 8, human,hiv,polymerase chain reaction,serology

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