HHV8 and Kaposi's sarcoma: a time cohort study.

Kennedy, M.; Lucas, Sebastian; Jones, RR; Howells, D; Picton, Steve; Hanks, E.; McGee, J O; O’Leary, John

doi:10.1136/mp.50.2.96

Cited by 27 publications

(16 citation statements)

References 44 publications

(4 reference statements)

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“…Cidofovir had the greatest inhibitory activity against HHV-8 (50% inhibitory concentration [IC 50 ], 0.43 M) followed by ganciclovir (2.61 M), adefovir (18.00 M), acyclovir (31.00 M), and foscarnet (34.15 M). The potential therapeutic efficacy for HHV-8 (i.e., peak serum drug level/IC 50 ) is highest for cidofovir (167) and foscarnet (22).The human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, is a new member of the ␥-herpesvirinae subfamily that has been associated with human immunodeficiency virus (HIV)-and non-HIV-related Kaposi's sarcoma (KS) as well as with multicentric Castleman's disease and primary effusion lymphoma (5,6,17,25). Despite the decrease in HIV-related KS with the advent of highly active antiretroviral therapy, there is still an interest in evaluating strategies to inhibit the early stages of HHV-8 replication.…”

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confidence: 99%

“…The human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, is a new member of the ␥-herpesvirinae subfamily that has been associated with human immunodeficiency virus (HIV)-and non-HIV-related Kaposi's sarcoma (KS) as well as with multicentric Castleman's disease and primary effusion lymphoma (5,6,17,25). Despite the decrease in HIV-related KS with the advent of highly active antiretroviral therapy, there is still an interest in evaluating strategies to inhibit the early stages of HHV-8 replication.…”

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confidence: 99%

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Evaluation of Susceptibility of Human Herpesvirus 8 to Antiviral Drugs by Quantitative Real-Time PCR

Sergerie

Boivin

2003

J Clin Microbiol

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A new in vitro system based on real-time PCR was developed for evaluation of human herpesvirus 8 susceptibility to antiviral agents. Cidofovir had the greatest inhibitory activity against HHV-8 (50% inhibitory concentration [IC 50 ], 0.43 M) followed by ganciclovir (2.61 M), adefovir (18.00 M), acyclovir (31.00 M), and foscarnet (34.15 M). The potential therapeutic efficacy for HHV-8 (i.e., peak serum drug level/IC 50 ) is highest for cidofovir (167) and foscarnet (22).The human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, is a new member of the ␥-herpesvirinae subfamily that has been associated with human immunodeficiency virus (HIV)-and non-HIV-related Kaposi's sarcoma (KS) as well as with multicentric Castleman's disease and primary effusion lymphoma (5,6,17,25). Despite the decrease in HIV-related KS with the advent of highly active antiretroviral therapy, there is still an interest in evaluating strategies to inhibit the early stages of HHV-8 replication.Several in vitro systems have been reported for determination of HHV-8 susceptibility to antiviral drugs (10,16,20,22). Because most B cells are latently infected by the virus, inducing agents such as 12-O-tetradecanoylphorbol-13-acetate (TPA) or sodium butyrate have been used to promote lytic viral replication (23). Also, due to the absence of viral plaques in infected lymphoma cell lines, most susceptibility systems were designed to measure viral DNA synthesis. However, the existing assays are very cumbersome, as they require gel electrophoresis and isotopic hybridization. In this report, we describe the development of a rapid and objective in vitro susceptibility system for HHV-8 based on real-time quantitative PCR.The BCBL-1 cell line, which is a B-cell line latently infected by HHV-8 (23), was kindly provided by Benoît Barbeau (Centre de Recherche en Infectiologie, Ste-Foy, Québec, Canada). The cells were maintained as described previously (16). On day 1, 10 ml of BCBL-1 cells at 2 ϫ 10 5 cells/ml (in RPMI 1640 medium [Life Technologies, Burlington, Ontario, Canada] supplemented with 10% heat-inactivated fetal bovine serum) were pelleted at 250 ϫ g for 10 min and then washed with 2 ml of phosphate-buffered saline. The cell pellet was then resuspended in an equal volume of medium with TPA (without TPA for the negative control) at a final concentration of 20 ng/ml in 25-cm 2 flasks (BD Biosciences, Oakville, Ontario, Canada). Serial concentrations of antivirals, i.e., acyclovir (zovirax; GlaxoSmithKline), foscarnet (Sigma, Oakville, Ontario, Canada), ganciclovir (cytovene; Hoffman La Roche), cidofovir (vistide; Gilead Sciences, Foster City, Calif.), and adefovir (kindly provided by Tomas Cihlar; Gilead Sciences) were made in triplicate and added to culture medium. On day 2, 20 h after TPA stimulation, the cells were repelleted as described above, washed with phosphate-buffered saline, and resuspended in 10 ml of fresh medium containing the same antiviral drugs but without TPA. On day 4 (3 days after the addition of TPA...

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Evaluation of Susceptibility of Human Herpesvirus 8 to Antiviral Drugs by Quantitative Real-Time PCR

Sergerie

Boivin

2003

J Clin Microbiol

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“…The sensitivity and specificity of the assay were tested with a series of clinical specimens obtained from patients affected by various HHV-8-related diseases, as well as from a wide number of controls. In conclusion, our calibrated real-time PCR assay provides a reliable high-throughput method for quantitation of HHV-8 DNA in clinical and laboratory specimens.Human herpesvirus 8 (HHV-8) is a recently characterized gamma herpesvirus associated with the development of Kaposi's sarcoma (KS), body-cavity-based-lymphoma (BCL), and some forms of multicentric Castleman's disease (MCD) (6,14,40). This virus is distributed worldwide with five distinct subtypes (A to E); yet, unlike other human herpesviruses, HHV-8 is not ubiquitous.…”

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confidence: 99%

“…Human herpesvirus 8 (HHV-8) is a recently characterized gamma herpesvirus associated with the development of Kaposi's sarcoma (KS), body-cavity-based-lymphoma (BCL), and some forms of multicentric Castleman's disease (MCD) (6,14,40). This virus is distributed worldwide with five distinct subtypes (A to E); yet, unlike other human herpesviruses, HHV-8 is not ubiquitous.…”

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Calibrated Real-Time PCR Assay for Quantitation of Human Herpesvirus 8 DNA in Biological Fluids

Broccolo¹,

Locatelli²,

Sarmati³

et al. 2002

J Clin Microbiol

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Accurate laboratory tests for the diagnosis of active human herpesvirus 8 (HHV-8) infection are becoming essential to study the pathogenesis of HHV-8-associated tumors and for the clinical management of HHV-8-infected individuals. We have developed a highly sensitive, calibrated quantitative real-time PCR assay for the measurement of cell-free HHV-8 DNA in body fluids, based on the addition of a synthetic DNA calibrator prior to DNA extraction. The calibrator controls each sample for the presence of PCR inhibitors, determines a cutoff value of sensitivity for negative samples, and normalizes positive samples for the efficiency of DNA recovery. The assay shows a wide dynamic range of detection (between 1 and 10 6 viral genome equivalents/reaction) and a high degree of accuracy even in the presence of high amounts (up to 1 g) of human genomic DNA. Moreover, the assay has a very high sensitivity (lower detection limit, 10 genome equivalents/ml) and a high degree of reproducibility and repeatability with a coefficient of variation (CV) of <15 and 23%, respectively. Furthermore, the use of the calibrator improves the accuracy of quantitation and decreases the intersample variability (CV, 9 and 6%, respectively). The sensitivity and specificity of the assay were tested with a series of clinical specimens obtained from patients affected by various HHV-8-related diseases, as well as from a wide number of controls. In conclusion, our calibrated real-time PCR assay provides a reliable high-throughput method for quantitation of HHV-8 DNA in clinical and laboratory specimens.Human herpesvirus 8 (HHV-8) is a recently characterized gamma herpesvirus associated with the development of Kaposi's sarcoma (KS), body-cavity-based-lymphoma (BCL), and some forms of multicentric Castleman's disease (MCD) (6,14,40). This virus is distributed worldwide with five distinct subtypes (A to E); yet, unlike other human herpesviruses, HHV-8 is not ubiquitous. Sero-epidemiological studies demonstrated a low prevalence of anti-HHV-8 antibodies in the general population in the United States and Asia (1 to 2%), an intermediate seroprevalence in Italy and other Mediterranean countries (5 to 35%), and the highest seroprevalence in Southern and Central Africa (30 to 60%) and among Brazilian Amerindians (41 to 65%) (1,4,8,19,31,35,38,39,46). HHV-8 seroconversion is associated, in some instances, with KS development (9). In addition, HHV-8 seropositivity can predict progression to KS in human immunodeficiency virus (HIV)-seropositive homosexual men (13,26,33).A variety of serological assays for diagnosis of HHV-8 infection have been described, but most of them fall short in sensitivity, specificity, and interassay concordance. Indeed, a combination of several assays should be utilized in order to obtain the optimal sensitivity and specificity (7,35,41). Moreover, the assessment of titers of antibody in serum may not always provide useful clinical information, especially for the therapeutic management of patients, since it does not allow distinguishing ...

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“…We analyzed a sample of DNA (1 mg) extracted from PBMC and plasma fractions by means of the QIAamp Blood Kit (Quiagen) and used PCR b-globin amplification of DNA samples as controls. We used the Taqman-based technique (Biosystem) of Kennedy et al [3] to detect EBV DNA, as described by Kimura et al [4], and to detect HHV-8 DNA, as described elsewhere [5]. Virus load was estimated from standard curves established from dilutions of DNA from the Namalwa (Burkitt) cell line (for EBV) and diluted plasmid controls (for HHV-8).…”

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Epstein‐Barr Virus and Human Herpesvirus 8 Coinfection and Concomitant Extranodal Nasal‐Type NK/T Cell Lymphoma and Castleman Disease: Case Report

Larroche

Agbalika²,

Poirel

et al. 2003

CLIN INFECT DIS

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We describe a 36-year-old man uninfected with human immunodeficiency virus who had confirmed concurrent infection with Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) and their respective lymphoproliferative manifestations, nasal-type NK/T cell lymphoma and Castleman disease. Antibodies to HHV-8 and EBV DNA were found in plasma and peripheral blood mononuclear cells. An EBV-positive nasal-type NK/T cell lymphoma infiltrated the splenic red pulp, whereas the white pulp contained HHV-8-positive plasmablasts, as found in Castleman disease.

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HHV8 and Kaposi's sarcoma: a time cohort study.

Cited by 27 publications

References 44 publications

Evaluation of Susceptibility of Human Herpesvirus 8 to Antiviral Drugs by Quantitative Real-Time PCR

Evaluation of Susceptibility of Human Herpesvirus 8 to Antiviral Drugs by Quantitative Real-Time PCR

Calibrated Real-Time PCR Assay for Quantitation of Human Herpesvirus 8 DNA in Biological Fluids

Epstein‐Barr Virus and Human Herpesvirus 8 Coinfection and Concomitant Extranodal Nasal‐Type NK/T Cell Lymphoma and Castleman Disease: Case Report

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