Detection of Human Herpesvirus-8 DNA in Kidney Allografts Prior to the Development of Kaposi's Sarcoma

Sarid, Ronit; Pizov, Galina; Rubinger, Deborah; Backenroth, Rebecca; Friedlaender, Michael M.; Schwartz, Fidi; Wolf, Dana

doi:10.1086/320153

Cited by 36 publications

(20 citation statements)

References 11 publications

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“…[5][6][7] Either neoplastic or non-neoplastic HHV8-related posttransplant diseases can also be the result of primary infections in patients showing HHV8-seroconversion after receiving allografts from HHV8-seropositive donors. 8 Notably, HHV8 ϩ cells may be harbored in the transplanted organ and transmit the virus to the recipient, 9,10 or, rather, KS tumors themselves may directly originate from donorderived HHV8 ϩ cells, seeded with the graft and then proliferating in the immunosuppressed recipient. 11…”

Section: Biologic Aspectsmentioning

confidence: 99%

How I treat HHV8/KSHV-related diseases in posttransplant patients

Riva¹,

Luppi²,

Barozzi³

et al. 2012

Blood

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Posttransplantation human herpesvirus-8 (HHV8)/Kaposi sarcoma herpesvirus (KSHV) primary infection and/or reactivations are associated with uncommon and sometimes fatal, neoplastic, and nonneoplastic diseases. HHV8-related clinical manifestations notably range from Kaposi sarcoma (KS) to either primary effusion lymphoma or multicentric Castleman disease B-cell malignancies, and from polyclonal HHV8-positive plasmacytic lymphoproliferative disorders to bone marrow failure and peripheral cytopenias, associated or not with hemophagocytic syndromes, and to acute hepatitis syndromes. We reviewed the patient series reported in the literature and summarized clinical management aspects, in terms of diagnosis, follow-up, and treatment. We described typical clinical presentations and histopathologic diagnostic features of these diseases, and we discussed the role of HHV8-specific serologic, molecular, and immunologic assays, particularly focusing on recent data from HHV8-specific T-cell monitoring in posttransplantation KS patients. We finally discussed actual therapeutic options, namely, the reduction or discontinuation of immunosuppressive therapy or the switch from calcineurin inhibitors to mTOR inhibitors, as alternatives to antineoplastic chemotherapy, along with the use of antiherpesvirus agents as prophylactic or therapeutic measures, and treatment with rituximab in posttransplantation multicentric Castleman disease patients and non-neoplastic HHV8-associated syndromes. IntroductionHerpesvirus-associated hematologic diseases often represent primary clinical challenges during the multidisciplinary follow-up of posttransplant patients, either with hematopoietic stem cell transplant (HSCT) or with solid organ transplant (SOT). In immunosuppressed organ recipients, latent human ␥-herpesvirus, namely, EBV and human herpesvirus-8 (HHV8)/Kaposi sarcoma herpesvirus (KSHV) are typically responsible for several virus-driven neoplastic proliferations, as well as they may sometimes cause uncommon, but equally life-threatening, non-neoplastic infectious complications. During the past decade, large amounts of experimental evidence have come out on these topics, and some of them have yet begun to influence the clinical behavior, in terms of diagnosis and treatment. Chiefly, EBV-related complications have been extensively studied and discussed, so that now physicians can rely on accurate and updated clinical recommendations, in particular dealing with early diagnosis, monitoring and treatment of EBV ϩ posttransplantation lymphoproliferative diseases (PTLDs). 1 With regards to HHV8, practical management of the virus-associated neoplastic lymphoproliferations has deeply been revised in HIVpositive subjects, 2,3 whereas in SOT and HSCT settings, the diagnostic and therapeutic issues about the various HHV8-driven manifestations (either neoplastic or non-neoplastic) are only occasionally reported in the literature, but most of these diseases revealed to be rapidly lethal if not timely recognized and adequately treated. Indeed, posttra...

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Section: Biologic Aspectsmentioning

confidence: 99%

How I treat HHV8/KSHV-related diseases in posttransplant patients

Riva¹,

Luppi²,

Barozzi³

et al. 2012

Blood

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“…In fact, end-stage renal disease and kidney dialysis were found to be risk factors for KSHV seropositivity (11). In a case report, Sarid et al proposed that the kidney may be a site of latent KSHV, describing two KSHV-seronegative patients who received infected kidney tissue, seroconverted, and subsequently developed KS; a third patient was weakly seropositive prior to transplantation and seemed to reactivate a latent KSHV infection within 1 year (445).…”

Section: Iatrogenic Ksmentioning

confidence: 99%

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Dourmishev

Palmeri

et al. 2003

Microbiol Mol Biol Rev

309

367

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Kaposi's sarcoma had been recognized as unique human cancer for a century before it manifested as an AIDS-defining illness with a suspected infectious etiology. The discovery of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, in 1994 by using representational difference analysis, a subtractive method previously employed for cloning differences in human genomic DNA, was a fitting harbinger for the powerful bioinformatic approaches since employed to understand its pathogenesis in KS. Indeed, the discovery of KSHV was rapidly followed by publication of its complete sequence, which revealed that the virus had coopted a wide armamentarium of human genes; in the short time since then, the functions of many of these viral gene variants in cell growth control, signaling apoptosis, angiogenesis, and immunomodulation have been characterized. This critical literature review explores the pathogenic potential of these genes within the framework of current knowledge of the basic herpesvirology of KSHV, including the relationships between viral genotypic variation and the four clinicoepidemiologic forms of Kaposi's sarcoma, current viral detection methods and their utility, primary infection by KSHV, tissue culture and animal models of latent- and lytic-cycle gene expression and pathogenesis, and viral reactivation from latency. Recent advances in models of de novo endothelial infection, microarray analyses of the host response to infection, receptor identification, and cloning of full-length, infectious KSHV genomic DNA promise to reveal key molecular mechanisms of the candidate pathogeneic genes when expressed in the context of viral infection

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“…This study suggested that direct genotypic and serologic analyses in kidney allografts in primary infection or increased viral antibody can predict the development of KS. Therefore, monitoring the transplant recipient for HHV-8 infection could be used to provide effective antiviral therapy (259).…”

Section: Transplantation Risksmentioning

confidence: 99%

Spectrum of Kaposi's Sarcoma-Associated Herpesvirus, or Human Herpesvirus 8, Diseases

Ablashi¹,

Chatlynne²,

Whitman³

et al. 2002

Clin Microbiol Rev

278

182

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Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), discovered in 1994, is a human rhadinovirus (gamma-2 herpesvirus). Unlike other human herpesviruses (herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, cytomegalovirus, HHV-6, and HHV-7), it is not widespread in the general population and has many unique proteins. HHV-8 is strongly associated with all subtypes of Kaposi's sarcoma (KS), multicentric Castleman's disease, and a rare form of B-cell lymphoma, primary effusion lymphoma. In addition, HHV-8 DNA sequences have been found in association with other diseases, but the role of the virus in these diseases is largely unconfirmed and remains controversial. The seroprevalence of HHV-8, based on detection of latent and lytic proteins, is 2 to 5% in healthy donors except in certain geographic areas where the virus is endemic, 80 to 95% in classic KS patients, and 40 to 50% in HIV-1 patients without KS. This virus can be transmitted both sexually and through body fluids (e.g., saliva and blood). HHV-8 is a transforming virus, as evidenced by its presence in human malignancies, by the in vitro transforming properties of several of its viral genes, and by its ability to transform some primary cells in culture. It is not, however, sufficient for transformation, and other cofactors such as immunosuppressive cytokines are involved in the development of HHV-8-associated malignancies. In this article, we review the biology, molecular virology, epidemiology, transmission, detection methods, pathogenesis, and antiviral therapy of this newly discovered human herpesvirus

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Detection of Human Herpesvirus-8 DNA in Kidney Allografts Prior to the Development of Kaposi's Sarcoma

Cited by 36 publications

References 11 publications

How I treat HHV8/KSHV-related diseases in posttransplant patients

How I treat HHV8/KSHV-related diseases in posttransplant patients

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Spectrum of Kaposi's Sarcoma-Associated Herpesvirus, or Human Herpesvirus 8, Diseases

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