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      Higher Levels of Neutralizing Antibodies against KSHV in KS Patients Compared to Asymptomatic Individuals from Zambia

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          Abstract

          Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi Sarcoma (KS), the most common cancer diagnosed in HIV- infected patients. The role of neutralizing antibodies in KS pathogenesis and in KSHV infected individuals is not clearly understood. The goal of this study was to investigate and compare the prevalence and titers of neutralizing antibodies in plasma samples from KS patients and KSHV infected asymptomatic individuals from Zambia, a KS endemic region in sub-Saharan Africa. Plasma samples (N = 267) consisting of KS patients (group 1) and asymptomatic individuals (group 2) were collected from Lusaka, Zambia. A flow cytometry based quantitative neutralization assay utilizing recombinant KSHV expressing GFP was used to detect KSHV neutralizing antibodies. Our results show that the overall prevalence of neutralizing antibodies in KS patients (group 1) was 66.7% which was significantly higher than the prevalence of 6.5% present in KSHV infected asymptomatic individuals (group 2). Total antibody titers as well as neutralizing antibodies titers were found to be significantly higher among KS patients. It is likely that higher neutralizing antibodies prevalence and titers in KS patients result from higher levels of antigenic stimulation over time. This study is first to compare prevalence and titers of neutralizing antibodies in participants with and without disease from a KSHV endemic region.

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          Most cited references19

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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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            Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma.

            Kaposi sarcoma-associated herpesvirus (KSHV) is consistently found in biopsy samples from patients with AIDS-related and "classical" Kaposi's sarcoma (KS). Although highly suggestive of a causal role of KSHV in the pathogenesis of KS, this observation does not exclude the possibility that KSHV, like other herpesviruses, is widely distributed and is a mere "passenger" in these lesions. Here we report that KSHV was detectable in peripheral blood mononuclear cells of 24/46 (52%) of KS patients, but in none of 134 blood donors or 26 HIV-uninfected hospital controls. KSHV detection increased with immunosuppression, as shown by a correlation with a reduced number of CD4-positive T-cells. Moreover, KSHV detection in peripheral blood cells of HIV-infected individuals without KS predicted the subsequent appearance of KS lesions. 143 patients who did not have KS at the time of their first (or only) blood sample were followed up for a median of 30 months. Of the 11 who had been KSHV positive 6 developed KS compared with only 12 out of 132 who were KSHV negative. These findings are compatible with a causative role of KSHV in KS. KSHV was rarely detected in sputum and throat swabs of HIV-infected patients, providing a potential explanation for the apparently limited spread of this virus.
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              Kaposi's sarcoma: a result of the interplay among inflammatory cytokines, angiogenic factors and viral agents.

              B. Ensoli (1998)
              Kaposi's sarcoma (KS) is an angioproliferative disease occurring in 4 clinic-epidemiologic forms. Although the AIDS-associated KS (AIDS-KS) is the most aggressive, all forms of KS share the same immunological and histopathological features suggesting common etiological and pathogenic factors. Recent data indicate that at least in early stage KS is not a real sarcoma but an angiohyperplastic-inflammatory lesion mediated by inflammatory cytokines and angiogenic factors, that is triggered or amplified by infection with human herpesvirus-8. In addition, the human immunodeficiency virus type-1 Tat protein appears to be responsible for the higher grade of aggressiveness of AIDS-KS as compared to the other forms of KS. However, given time, reactive KS may progress to a sarcoma as suggested by evidence of monoclonality in late-nodular lesions.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                14 August 2013
                : 8
                : 8
                : e71254
                Affiliations
                [1 ]Nebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America
                [2 ]Department of Pathology and Microbiology, University of Zambia School of Medicine, Lusaka, Zambia
                [3 ]Department of Paediatrics, University of Zambia School of Medicine, Lusaka, Zambia
                Hannover Medical School, Germany
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: PK NK CW. Performed the experiments: PK NK VM DS. Analyzed the data: PK VM DS. Contributed reagents/materials/analysis tools: CM CK CW. Wrote the paper: PK NK VM CW. Obtained permission for use of cell line: NK CW.

                Article
                PONE-D-13-09427
                10.1371/journal.pone.0071254
                3743886
                23967174
                b64431ca-3c4e-459f-ab7b-490dda0566a9
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 March 2013
                : 27 June 2013
                Page count
                Pages: 7
                Funding
                This work was supported by The National Institutes of Health (PHS grant number RO1 CA75903); Fogarty International Training Grant (D43 TW01492 and T32 AI060547) and The Centers of Biomedical Research Excellence grant (P30GM103509) to CW. CM has been a Fogarty Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Microbiology
                Virology
                Viral Immune Evasion
                Viruses and Cancer
                Medicine
                Clinical Immunology
                Immunoglobulins
                Epidemiology
                Infectious Disease Epidemiology
                Infectious Diseases
                Viral Diseases
                HIV
                HIV opportunistic infections
                Oncology
                Cancers and Neoplasms
                Bone and Soft Tissue Sarcomas
                Kaposi Sarcoma

                Uncategorized
                Uncategorized

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