Human herpesvirus type 8 infection in an area of Northern Italy with high incidence of classical Kaposi's sarcoma

Previous studies have reported a large variation in the incidence of classical Kaposi's sarcoma across different Districts of the province of Mantua (Northern Italy). To assess whether such differences might be explained by different anti-HHV8 antibody prevalence, a serological study was conducted in 343 healthy elderly individuals resident in two adjacent Districts, at the highest and the lowest classical Kaposi's sarcoma incidence rate, respectively. Qualitative and quantitative determinations of IgG antibodies against both latent and lytic HHV-8 antigens were performed by indirect immunofluorescence assay. The assay's sensitivity was studied in 26 patients with classical Kaposi's sarcoma. Overall, anti-HHV8 antibodies were detected in 25 out of 26 patients (96%), confirming the high sensitivity of this assay. The prevalence of anti-HHV-8 antibodies was higher among individuals living in the District had a high incidence of classical Kaposi's sarcoma compared to those living in the District with low incidence (19.4% vs 9.8%, and 15.9% vs 8%; P<0.05, for latent and lytic antibodies, respectively). Anti-lytic antibody GMT was higher in people living in the District at high incidence rate compared to those of the other area (328.9 vs. 180.4; P<0.01). A higher prevalence of HHV-8 infection was found among persons living in municipalities surrounded by watercourses (OR 2.2, 95% CI: 1.10-4.32). In conclusion, variation in HHV-8 prevalence appears to explain differences in the incidence rates of classical Kaposi's sarcoma observed in different areas of the province.     

High prevalence of human herpesvirus 8 (HHV-8) infection in south Texas children

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, is etiologically associated with Kaposi's sarcoma and other rare malignancies. HHV-8 infection is common in certain areas of Africa and Italy, but occurs in only 0-15% of populations in North America and Europe. The epidemiology and prevalence of HHV-8 infection among children in the United States has not been determined, but is assumed to be low based on limited studies. The objective of this study was to determine the seroprevalence and possible risk factors of HHV-8 infection in children living in south Texas. Questionnaire data were collected and HHV-8 serologic tests were performed from a consecutive, non-probability sample of 123 healthy children (ages 4-13 years) attending general pediatric clinics in south Texas. Serum was tested for HHV-8 antibodies by latent immunofluorescence assay and ORF65 enzyme-linked immunosorbent assay confirmed by immunoblot. HHV-8 prevalence and 95 percent confidence intervals were calculated using standard epidemiologic methods. Logistic regression was used to assess independent risk factors associated with HHV-8 seropositivity. The overall prevalence of HHV-8 infection was 26%. No statistically significant associations were exhibited between HHV-8 prevalence and the variables under study. The prevalence of HHV-8 infection among children in south Texas, particularly among those under the age of 12 years, indicates that non-sexual transmission of this virus is likely to occur among this population. Future investigations of larger study samples will be necessary to develop an understanding of specific routes and risk factors of HHV-8 transmission among children in south Texas.     

Comparison of human herpesvirus 8 and Epstein-Barr virus seropositivity among children in areas endemic and non-endemic for Kaposi's sarcoma

Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS). Several studies indicate horizontal HHV-8 transmission among children in areas where KS is endemic, but few studies have assessed acquisition of HHV-8 by children in low seroprevalence areas. Antibody screening was carried out for HHV-8 and Epstein-Barr virus (EBV) on 787 serum specimens from children living in two areas where HHV-8 is not endemic, the United States (US) and Germany, and on 184 specimens from children living in a KS-endemic area (Nigeria). For children in the US and Germany, the results showed low HHV-8 seroprevalence rates (3-4%). However, US children aged 6 months to 5 years had higher HHV-8 antibody titers than did 6-17-year-old children (P < 0.01), a finding consistent with more recent infections being detected in the younger children. Compared with seroprevalence rates and antibody titers in US and German children, those in Nigerian children were significantly higher, and seroprevalence increased with age. There was no evidence of cross-reactivity between assays for HHV-8 and EBV, despite the genetic similarity of these two herpesviruses. The data indicate that HHV-8 transmission among children where HHV-8 is not endemic occurs, but is uncommon. The findings also suggest that HHV-8 antibodies, as measured by current tests, may not persist for long periods in populations at low risk for KS and that vertical transmission is rare, although longitudinal studies are necessary to address directly these issues.     

Seroprevalence of human herpesvirus 8 in human immunodeficiency virus 1-positive and human immunodeficiency virus 1-negative populations in Japan

To determine the seroprevalence of human herpesvirus 8 (HHV8) among human immunodeficiency virus 1 (HIV-1)-positive (HIV-1⁺) and HIV-1-negative (HIV-1⁻) populations in Japan, 276 HIV-1⁺ patients and 1,000 HIV-1⁻ blood donors were enrolled in this study. Antibodies against HHV8 latency-associated nuclear antigen (LANA) were examined through indirect immunofluorescent assay by using a B-cell line that was infected latently with HHV8 (body cavity-based lymphoma 1). An HHV8⁻ and Epstein-Barr virus-negative B-cell line (Ramos) was used as a control. Thirty-two seropositive cases against LANA (anti-LANA⁺) were identified among the 276 HIV-1⁺ patients who were studied. Five cases were foreigners living in Japan. The risk factor of all 27 Japanese cases was unprotected sexual intercourse, and the great majority of these cases (23 in 27; 85%) reported homosexual/bisexual behavior. Anti-LANA⁺ status correlated with the presence of sexually transmitted diseases, such as amoeba and HBV infection, further suggesting male homosexual behavior as the main route of HHV8 transmission in Japan. Only two LANA⁺ cases were identified among 1,000 HIV⁻ blood donors in Japan; thus, seroprevalence of HHV8 identified by LANA was estimated to be 0.2% among HIV-1⁻ populations in this country. J. Med. Virol. 57:159–162, 1999. © 1999 Wiley-Liss, Inc.     

Human herpesvirus 8 shedding in the mouth and blood of hemodialysis patients

In Saudi Arabia, the prevalence of transplantation‐associated Kaposi's sarcoma (KS) is high, and there is disparity in the prevalence rates of human herpesvirus 8 (HHV‐8) infection between patients with renal disease and the general population. It was hypothesized that oral HHV‐8 transmission among patients undergoing hemodialysis treatment contributes to the high prevalence of infection in renal disease patients. The detection rates of anti‐HHV8‐IgG in plasma and HHV‐8‐DNA in CD45(+)‐peripheral blood cells of 72 hemodialysis patients were compared first with those of 178 blood donors and 60 pregnant women. Between the hemodialysis patients and the apparently healthy people sampled, the detection rate of anti‐HHV‐8‐IgG was 16.7% versus 0.4% (P < 0.001) and that of HHV‐8‐DNA was 4.2% versus 0.4%, (P < 0.05). HHV‐8 DNA was determined in oral samples and the HHV‐8 viral load measured in saliva of patients undergoing hemodialysis. The amount of virus shed into saliva ranged between 8,600 and 119,562,500 (mean: 24,009,360) genome‐equivalents/ml among the five patients in whom oral HHV‐8 DNA was detected. Finally, HHV‐8‐subgenomic sequencing was conducted which showed that orally shed HHV‐8 in four patients belonged to genotype C2, and in one patient to genotypes A1 and C2. HHV‐8 shed in the mouth of hemodialysis patients may be extensive and diverse. Oral fluid in addition to blood is thus a likely vehicle for transmission of HHV‐8, possibly contributing to the high risk of HHV‐8 infection in patients undergoing hemodialysis and to KS following immunosuppression after renal transplantation. J. Med. Virol. 84:792–797, 2012. © 2012 Wiley Periodicals, Inc.     

Seroprevalence of Kaposi's sarcoma‐associated herpesvirus and risk factors in Xinjiang,China

Xinjiang, China is an endemic area for Kaposi's sarcoma (KS) but the seroprevalence of Kaposi's sarcoma‐associated herpesvirus (KSHV) and risk factors remain undefined. In this study, antibodies to one KSHV latent protein (ORF73) and two KSHV lytic proteins (ORF65 and ORF‐K8.1) were examined in 2,228 subjects from the general population and 37 subjects infected with HIV‐1 in Xinjiang, and 560 subjects from the general population in Hubei, a low KS incidence region. The serostatus of a serum sample was defined based on positive results in any one of the three serologic assays. The seroprevalence of KSHV in the general population was higher in Xinjiang than in Hubei (19.2% vs. 9.5%; odds ratios [OR], 2.28; 95% confidence interval [CI], 1.68–3.08; P < 0.001). Among the ethnic groups in Xinjiang, 68 (15.8%) Han, 182 (20.7%) Uygur, 140 (19.9%) Hazakh, 9 (33.3%) Xibo, and 29 (16.8%) Hui were KSHV‐seropositive, respectively. Compared to the Han, the latter groups had an increase in the risk of KSHV of 62.2%, 63.8%, 180.1%, and 30.2% (P = 0.003, 0.004, 0.018, and 0.286, respectively). Subjects aged <20, 20–50, and >50 had a seroprevalence of KSHV of 11.8%, 17.9%, and 24.6%, respectively. Compared to subjects aged <20, the latter groups had an increase in the risk of KSHV of 63.3% and 144.5% (P = 0.009 and <0.001, respectively). Subjects infected with HIV‐1 in Xinjiang had a seroprevalence of KSHV of 43.2%, and a 220% increase in the risk of KSHV compared to the general population (P < 0.001). Similar results were obtained when the seroprevalence of KSHV was analyzed with any single or two of the three serologic assays alone. Genotyping identified three unique sequences clustered in the A clade. This study indicates that Xinjiang has a high seroprevalence of KSHV. Geographic location, ethnicity, age and HIV‐1 infection are risk factors. Serologic and genotyping results suggest the introduction of KSHV into Xinjiang by specific ethnic groups. J. Med. Virol. 81:1422–1431, 2009. © 2009 Wiley‐Liss, Inc.     

Prevalence of, and risk factors for Kaposi's sarcoma-associated herpesvirus infection among blood donors in Brazil: a multi-center serosurvey

Kaposi's sarcoma-associated herpesvirus (KSHV) is endemic in the Amazon and rare in southern regions of Brazil. However, geographical distribution and epidemiological correlates of infection in this large country are still poorly defined. To estimate the seroprevalence of, and risk factors for, KSHV infection in Brazil, a multi-center study was conducted among 3,493 first-time voluntary unpaid blood donors from Salvador, Sao Paulo and Manaus. Antibodies against KSHV were detected using a whole-virus ELISA validated prior to the serosurvey. Antibodies against the latency-associated nuclear antigen (LANA) were detected by immuno-fluorescence assay (IFA) among ELISA-positive sera and a random sample of ELISA-negative sera. Overall, seroprevalence of KSHV by whole-virus ELISA was 21.7% (95% confidence interval (CI): 20-23.4%) in men and 31.7% (95% CI: 29-34.3%) in women (P<0.0001). KSHV antibodies were detected by IFA-LANA in 3% (95% CI: 2-4.3%) of 867 ELISA-positive samples and in none of 365 randomly selected ELISA-negative samples. In multivariate analysis, KSHV seroprevalence by whole-virus ELISA was independently associated with female sex (odds ratio [OR]=1.6, 95% CI: 1.4-1.9); residence in the Amazon (OR=1.4, 95% CI: 1.2-1.8; compared to Salvador); Caucasian ethnicity (OR=1.3, 95% CI: 1.1-1.6) and herpes simplex virus type 2 (HSV-2) infection (OR=1.3, 95% CI: 1.1-1.6). KSHV seroprevalence did not significantly increase with age, nor was it associated with self-reported sexual behavior. KSHV seroprevalence is high among Brazilian blood donors, particularly from the Amazon region. This study supports the co-existence of sexual and non-sexual routes of KSHV transmission in this population.     

Human herpesvirus 8 genoprevalence in populations at disparate risks of Kaposi's sarcoma

The prevalence of human herpesvirus 8 (HHV-8) in populations at different risks of developing Kaposi's sarcoma (KS) was assessed using a protocol involving immunomagnetic fractionation of CD45+ blood cells prior to detection of the HHV-8 genome by nested PCR. Preliminary studies using blood of eight gay men infected by human immunodeficiency virus-1 (HIV-1) revealed that, for the detection of HHV-8 DNA derived from open reading frame (ORF) 26 of the HHV-8 genome, this protocol provided substantially higher rates (100%) compared to one involving red blood cell (RBC) lysis (0%) and to another requiring double density gradient centrifugation (DDGC) of leukocytes (13%). When the CD45+ fractionation protocol was applied to samples from 103 other HIV-1-infected patients (the vast majority of whom were gay men) and 100 blood donors, the ORF 26 DNA detection rates obtained were 37% and 8%, respectively. When DNA from the variable region 1 of ORF K1 was additionally amplified from samples of the blood donors, a detection rate of 9% was achieved. This rate was highly concordant with the ORF 26 DNA detection rate. Furthermore, the ORF K1 sequences were predominantly unique, assignable to genotypes A1, A4, and C3. When assays for anti-HHV-8 and anti-herpes simplex viruses (HSV) 1 and 2 were applied, significant concordances between HHV-8 DNA detection rates and those relating to anti-HHV-8 and to anti-HSV 1 and 2 were more frequently observed for HIV-1-infected patients than for blood donors. The higher-than-expected HHV-8 genoprevalence rate in blood donors requires further confirmation in view of its implications for post-transfusion HHV-8 transmission.     

Genotypic and clinicopathological characterization of Kaposi's sarcoma‐associated herpesvirus infection in Japan

Kaposi's sarcoma‐associated herpesvirus (KSHV) is related causally to Kaposi's sarcoma, primary effusion lymphoma, and a subset of cases of multicentric Castleman's disease. As the numbers of acquired immunodeficiency syndrome (AIDS) patients have increased, KSHV‐associated diseases have also increased in Japan. Sporadic cases of classic Kaposi's sarcoma have also been reported in Japan. In the present study, the clinicopathological characteristics of 75 samples, comprising 68 cases of Kaposi's sarcoma, 5 cases of primary effusion lymphoma, and 5 cases of multicentric Castleman's disease were investigated. All of these cases were positive for KSHV by immunohistochemistry or PCR analysis. All fifty‐two of the AIDS‐associated Kaposi's sarcoma cases were males, whereas 7 of the 13 non‐AIDS‐associated Kaposi's sarcoma cases were females. The mean age of patients with AIDS‐associated Kaposi's sarcoma or primary effusion lymphoma was 46 years, whereas the mean age of patients with non‐AIDS‐associated Kaposi's sarcoma or primary effusion lymphoma was 71.8 and 97.5, respectively. KSHV genotypes were determined based on the sequence of variable region 1 in the K1 gene. Genotypes A and C of KSHV were detected in both AIDS‐ and non‐AIDS‐associated Kaposi's sarcoma. Genotype A was detected more frequently in AIDS‐associated cases than non‐AIDS‐associated cases, suggesting that genotype C is broadly distributed in Japan, and genotype A spreads among AIDS patients. Genotype D was detected only in non‐AIDS‐associated Kaposi's sarcoma. These data confirmed the difference between AIDS‐ and non‐AIDS‐associated KSHV diseases with regard to age of onset, gender, and genotypes in Japan. J. Med. Virol. 82:400–406, 2010. © 2010 Wiley‐Liss, Inc.     

Salivary human herpesvirus 8 shedding in renal allograft recipients with Kaposi's sarcoma

Renal allograft recipients in the Middle East are at high risk of developing Kaposi's sarcoma. This report describes the extent of oral human herpesvirus 8 shedding and the genomic diversity of the virus in five Saudi Arabian kidney transplantation patients in whom Kaposi's sarcoma had developed. PCR protocols were applied to amplify three fragments of the viral genome from whole-mouth saliva, parotid saliva, buccal and palatal exfoliates, plasma, peripheral blood leukocytes and biopsy of the Kaposi's sarcoma lesion, and to quantify the viral load in whole-mouth saliva. Viral DNA was detected in all plasma and biopsy samples, 80% of whole-mouth saliva, 20% of each of the other oral samples, and none of the leukocyte samples. The viral load in the cell-free fraction of whole-mouth saliva ranged between approximately 1.2 x 10(3) and 2.2 x 10(6) genome-copies/ml. Genotypically distinct viral strains were evident: intra-lesionally in 1 patient; intra-orally in one patient; between an oral sample and biopsy in two patients; and in four patients, between an oral sample and plasma, and between plasma and biopsy. Thus, in the patients studied, salivary shedding of human herpesvirus 8 was frequent and could be extensive, and they were prone to multiple infections. Measures to curtail salivary viral transmission to pre- and post-transplantation patients might reduce the incidence of post-transplantation Kaposi's sarcoma.     

Diverse genotypes of Kaposi's sarcoma associated herpesvirus (KSHV) identified in infant blood infections in African childhood-KS and HIV/AIDS endemic region

Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) has been associated with several neoplasias, including childhood endemic Kaposi's sarcoma (KS). It is possible that strain genotypes could contribute to the differences in regional presentation (mainly sub-Saharan Africa), childhood infection, lack of male sex bias, distinct disseminated forms and rapid fatality observed for childhood endemic KS. Early studies, at the advent of the HIV/AIDS epidemic, identified only the K1-A5 genotype in childhood KS biopsies as well as blood of a few HIV positive and negative febrile infants in Zambia, a highly endemic region. This current enlarged study analyses blood infections of 200 hospitalized infants (6-34 months age) with symptoms of fever as well as upper respiratory tract infection, diarrhoea, rash or rhinitis. KSHV and HIV viraemia and were prevalent in this group, 22% and 39%, respectively. Multiple markers at both variable ends of the genome (K1, K12, and K14.1/K15) were examined, showing diverse previously adult-linked genotypes (K1 A2, A5, B, C3, D, with K12 B1 and B2 plus K14.1/K15 P or M) detected in both HIV positive and negative infants, demonstrating little restriction on KSHV genotypes for infant/childhood transmission in a childhood endemic KS endemic region. This supports the interpretation that the acquisition of childhood KSHV infections and subsequent development of KS are due to additional co-factors.     

Quantification of human herpesvirus 8 by real-time PCR in blood fractions of AIDS patients with Kaposi's sarcoma and multicentric Castleman's disease

Few studies have assessed human herpesvirus 8 (HHV8) viremia levels in different HHV8-related pathologies, using sensitive and reproducible molecular assays. Our objective was to compare the HHV8 DNA load in serial blood samples (collected every 3 months for 1 year) from acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS) and multicentric Castleman's disease (MCD). The HHV8 viral load was determined in both peripheral blood mononuclear cells (PBMC) and plasma fractions, using a competitive real-time polymerase chain reaction (PCR) assay developed in a LightCycler instrument (Roche Diagnostics). In six subjects with limited or extensive KS while on highly active antiretroviral therapy, the HHV8 DNA load was either undetectable (<50 copies/10(5) cells) or low (1,000 copies in at least one of the samples from the two subjects with both KS and MCD. HHV8 DNA was detected in plasma only when the cellular viral load was >10,000 copies/10(5) cells. After chemotherapy, the HHV8 DNA load became undetectable in the MCD patients despite no changes in CD4 T-cell counts or highly active antiretroviral therapy (HAART) regimens. These results suggest that the pathogenesis of the two HHV8-associated diseases (i.e., KS and MCD) might be different, as only the latter was associated with important viremia in our patients.     

Direct correlation between human herpesvirus-8 seroprevalence and classic Kaposi's sarcoma incidence in Northern Sardinia

The human herpesvirus-8 (HHV-8) has been associated with the development of Kaposi's sarcoma. A high incidence of classic Kaposi's sarcoma has been described in Sardinia, an island West of Italy's mainland. Different seroepidemiological analyses have reported that prevalence of HHV-8 infection varies worldwide: a high HHV-8 seroprevalence has been shown in Italy. The present survey was carried out to evaluate the correlation between HHV-8 infection and classic Kaposi's sarcoma incidence in northern Sardinia. Blood samples were collected from 226 healthy donors born and resident in five different areas of North Sardinia. Seroprevalence to HHV-8 was determined searching antibodies to viral lytic proteins by immunofluorescence in sera diluted at 1:10. Classic Kaposi's sarcoma incidence data spanning a period of 23 years were examined in the areas studied. The present screening revealed that seroprevalence was 35%, within a range of 15.3-46.3% in the five areas, although it should be considered that the seroprevalence to HHV-8 can be established more accurately by the combined use of different assays. Age emerged as an important risk factor. Indeed, subjects aged > 50 years showed a higher seroprevalence to HHV-8 as compared with younger individuals. A strong direct correlation between HHV-8 prevalence and classic Kaposi's sarcoma incidence has been also observed. The wide diffusion of HHV-8 in Sardinia appears to represent an important factor in the high incidence of classic Kaposi's sarcoma reported in the island. However, additional co-factors, such as age, sex, genetic traits, or viral strain pathogenicity, are likely to play a role in the development of the disease.     

Classic type of Kaposi's sarcoma and human herpesvirus 8 infection in Xinjiang, China

We report 17 cases of the classic type of Kaposi's sarcoma in Xinjiang, which is located in the north-western area of China surrounded by Mongolia in the east, Russia in the north and Kazakhstan in the west. Fifteen of the patients were of the Uygur people. All patients were male and did not have acquired immunodeficiency syndrome. Most of the lesions were found in the lower and/or upper extremities, with 16 patients showing multiple lesions. Immunohistochemical examination of the lesions revealed that human herpesvirus 8 (HHV-8)-encoded latency-associated nuclear antigen was expressed in the nuclei of spindle-shaped tumor cells. HHV-8 DNA was detected by polymerase chain reaction in all seven cases examined. Phylogenetic tree analysis revealed that DNA sequences of the HHV-8-encoded K1 gene in the seven Kaposi's sarcoma cases were classified as subtype C that was common in the Mediterranean, the Middle East and East Asian countries. In addition, using immunofluorescence we investigated the seroprevalence of HHV-8 in 73 Uygur patients with diseases other than Kaposi's sarcoma. Surprisingly, the serological study revealed that 34 of the patients (46.6%) were positive for antibodies against HHV-8, suggesting that HHV-8 infection is widespread in Xinjiang area. The occurrence of the classic type of Kaposi's sarcoma with a high seropositivity rate implies that Xinjiang is the most endemic area for HHV-8 infection in the world known to date. Considering that Xinjiang is located at the middle point of the Silk Road that used to extend from Rome to China, these data imply that the virus may have been in circulation in this area due to the migration of the people via the Silk Road.     

Kaposi's sarcoma-associated herpesvirus infection in Chinese patients with chronic hepatitis B

The seroprevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) in Chinese patients with chronic hepatitis B, the relationship between KSHV and hepatitis B virus (HBV) infection, and the influence of glycyrrhizic acid on KSHV replication in vivo are undefined. Plasma was collected from 211 patients with chronic hepatitis B. Antibody to KSHV ORF65 was evaluated by ELISA, and real-time PCR was used to quantify KSHV DNA and HBV DNA. The KSHV ORF65 positivity rate in patients with chronic hepatitis B was found to be 28% (59/211): 27.3% (44/161) in males and 30% (15/50) in females (P > 0.05). The seroprevalence of KSHV increased with age until reaching the highest rate (37.1%) in the 31-40 years age group. HBV DNA loads in patients with chronic hepatitis B infected with KSHV were higher than those without KSHV infection (9.2 log (10) IU/ml vs. 7.8 log (10) IU/ml, P < 0.05). The average KSHV DNA loads in patients with HBV genotype B, C, and mixed (B/C) were 409.1, 484.5, and 352 copies/ml, respectively (P > 0.05). Patients treated with glycyrrhizic acid had lower KSHV DNA levels than those without therapy (204.7 copies/ml vs. 533.9 copies/ml, P < 0.05). The KSHV ORF65 positivity rates tended to increase with age, but were not related to gender or HBV genotypes. The data indicated the interaction between KSHV and HBV, and the inhibiting effect of glycyrrhizic acid on KSHV replication in patients with chronic hepatitis B.     

Ultrastructural characterization of human herpesvirus 8 (Kaposi's sarcoma- associated herpesvirus) in Kaposi's sarcoma lesions: electron microscopy permits distinction from cytomegalovirus (CMV)

Kaposi's sarcoma (KS) has been shown by molecular techniques to be associated with infection with human herpesvirus 8 (HHV8/KSHV), but specific ultrastructural characterization of the virus has been impaired by the frequent presence in these lesions of other herpesviruses, particularly cytomegalovirus (CMV). Since the ultrastructural appearance of HHV8/KSHV has been studied in the cell line KS-1 uninfected with other viruses including CMV, it was possible to undertake a comparative study of CMV and HHV8/KSHV in KS lesions. HHV8/KSHV was sparsely present and lytic infection was restricted to endothelial cells. The following specific ultrastructural features allowed distinction between HHV8/KSHV and CMV: the viral particles were more delicate and less numerous in cases of HHV8/KSHV infection; the viral tegument was more electron-dense in CMV than in HHV8/KSHV; dense bodies characteristic of CMV were absent in HHV/KSHV; complete CMV viral particles were more variable in size and generally larger (150–200 nm) than HHV8/KSHV (120–150 nm); and finally, the viral envelope was more pleomorphic in CMV than in KSHV/HHV8. Similarities between CMV and HHV8/KSHV included the basic structure of the nucleocapsids and the presence of capsids lacking central DNA cores (so-called non-infectious enveloped particles). These observations show that electron microscopy can be used to identify HHV8/KSHV and confirm the relationship between HHV8/KSHV and KS. © 1997 John Wiley & Sons, Ltd.     

HHV8 a subtype is associated with rapidly evolving classic Kaposi's sarcoma

The link between human herpesvirus 8 (KSHV) and Kaposi's sarcoma (KS) has been proven, but many important aspects including risk factors, genetic predisposition to tumor development, transmission of KSHV, and the pathogenic potential of different genotypes remain to be elucidated. Possible associations between clinical parameters and antibody levels, viral load fluctuations, and viral genotype were analyzed by quantitative real‐time PCR, an in‐house developed IFA assay, and sequence analysis of ORF K1‐VR1 in blood, serum and saliva of 38 subjects with classic KS (cKS). KSHV lytic antibodies were significantly increased in stage IV compared to stage I and II patients (p = 0.006 and p = 0.041, respectively). KSHV blood, serum, and saliva viral load was comparable in all stages. The highest viral loads were detected in saliva, and they decreased in stages III–IV compared to stages I–II patients. Higher concentrations of lytic antibodies and higher viral loads were observed in fast progressing cKS patients, in whom KSHV detection from blood was also more frequent. Type A KSHV strain was almost exclusively present in rapid progressors (12/17 cases), while C type was mainly present in slow progressing patients (6/7 cases). Finally, detection of type A KSHV strain associated with higher blood viral loads. KSHV lytic antibody levels and viral load can be used to monitor clinical evolution of cKS. Infection supported by KSHV A subtype is associated with more rapid progressive disease. Careful monitoring and aggressive therapeutic protocols should be considered in patients with KSHV A‐supported infection. J. Med. Virol. 80:2153–2160, 2008. © 2008 Wiley‐Liss, Inc.