Kaposi's sarcoma herpesvirus is associated with osteosarcoma in Xinjiang populations.

Osteosarcoma is the most common malignant tumor of bone predominately affecting adolescents and young adults. Based on animal studies, a viral etiology of osteosarcoma was proposed more than a half-century ago, but no viral association with human osteosarcoma has been found. The Uyghur ethnic population in Xinjiang, China, has an unusually high prevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) infection and elevated incidence of osteosarcoma. In the current study, we explored the possible association of KSHV infection and osteosarcoma occurrence. Our seroepidemiological study revealed that KSHV prevalence was significantly elevated in Uyghur osteosarcoma patients versus the general Uyghur population (OR, 10.23; 95%CI, 4.25, 18.89). The KSHV DNA genome and viral latent nuclear antigen LANA were detected in most osteosarcoma tumor cells. Gene expression profiling analysis showed that KSHV-positive osteosarcoma represents a distinct subtype of osteosarcomas with viral gene-activated signaling pathways important for osteosarcoma development. We conclude that KSHV infection is a risk factor for osteosarcoma, and KSHV is associated with some osteosarcomas, representing a newly identified viral-associated endemic cancer.

Social behavioral correlates of Kaposi sarcoma-associated herpesvirus infection among Han and Uygur populations in Xinjiang, China.

BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) is endemic in Xinjiang, China and its prevalence varies considerably across ethnic groups. The current study explored the prevalence and correlates of KSHV infection among Han and Uygur populations in Xinjiang. METHODS: A cross-sectional study, including 282 Han ethnicity and 312 Uygur, was conducted in Xinjiang, China. All participants underwent face to face questionnaire interview. Plasma samples were collected and screened for KSHV infection using immunofluorescence assay. Univariate and multivariate analyses were conducted to examine the correlates of KSHV seropositivity. RESULTS: The KSHV seroprevalence was 41.6% (95% confidence interval [CI], 37.6-45.6) overall and was higher in the Uygur group (59.9%; 95% CI, 54.3-65.4) than the Han group (21.3%; 95% CI, 16.6-26.5). A significant difference in the geometric mean titer (GMT) of the KSHV antibodies was detected between the Uygur and Han groups (158.2; interquartile range [IQR], 80-320 vs 89.1; IQR, 40-160; P < 0.001). After adjusting for potential confounders, Uygur ethnicity (odds ratios [OR], 5.96; 95% CI, 4.05-8.90), age greater than or equal to 50 years (OR, 1.84; 95% CI, 1.24-2.77), and preference for meat diet (OR, 2.15; 95% CI, 1.05-4.46) were significantly associated with increased odds of KSHV seropositivity. CONCLUSION: The study demonstrated high prevalence and correlates of KSHV infection in both Han and Uygur populations in Xinjiang, China. There is an urgent need for programmatic adaptation to address primary prevention interventions of KSHV infection in this endemic region.

High prevalence of early childhood infection by Kaposi's sarcoma-associated herpesvirus in a minority population in China.

In China, KSHV seroprevalence varies considerably among different regions and ethnicities. But in Xinjiang province, located in the northwestern China, there is a very high seroprevalence of KSHV in adults of Kazak and Ughur ethnicities. However, KSHV prevalence in children and the risk factors associated with the acquisition of infection are currently not known. The aim of this study was to investigate the prevalence of KSHV infection and identify associated socioeconomic or behavioural risk factors and the humoral immune response among children in this population. This is a cross-sectional study (N = 178) to screen children and their caregivers from Xinjiang for total KSHV antibodies, KSHV neutralizing antibodies and HIV infection. Structured questionnaires were utilized to investigate risk factors associated with KSHV prevalence. KSHV seroprevalence in children and caregivers in Xinjiang was 48.3% and 64.7%, respectively. Neutralizing antibody was detected in most seropositive caregivers (93.8%) but was detected in only 5.8% of the infected children. A significant association was observed between child KSHV seroprevalence and sharing of food among family members. These results suggest that similar to other endemic areas in Africa, KSHV infection in the minority populations of Xinjiang is likely to be occurring during early childhood, probably via horizontal transmission through saliva, and results in high seroprevalence in the adult population.

Variations in human herpesvirus type 8 seroprevalence in Native Americans, South America.

To determine the epidemiology of human herpesvirus type 8 (HHV-8) among non-Amazonian native populations, we conducted a cross-sectional study in Brazil, Bolivia, and Paraguay. Our data show striking ethnic and geographic variations in the distribution of HHV-8 seroprevalences in Amazonian (77%) and non-Amazonian native populations (range 0%-83%).

The impact of preexisting or acquired Kaposi sarcoma herpesvirus infection in kidney transplant recipients on morbidity and survival.

The impact of preexisting or acquired Kaposi sarcoma herpesvirus (KSHV) infection in kidney transplant recipients was evaluated in a prospective study. Serum collected from kidney donors and recipients before transplantation were tested for antibodies against KSHV latent nuclear antigen. Three groups of recipients were defined: group A (KSHV+), group B (KSHV-, KSHV+ donor) and group C (donor and recipient KSHV-). Blood was collected from recipients, every 3 months for 3 years, for KSHV viremia (groups A and B), quantitative (group A) and qualitative serology (group B). Data of group C recipients were extracted from a French database. The prevalence of KSHV antibodies was 1.1% in donors and 3.2% in recipients. There were respectively 161, 64 and 4744 recipients in groups A, B and C. In group A, 13% developed Kaposi's sarcoma (KS). Age >53.5 years (p = 0.025) and black skin (p = 0.0054) were associated with KS development. In group B, three recipients developed clinical manifestations related to KSHV infection. There was no difference in terms of survival and graft loss between the three groups. In conclusion, although kidney recipients should be aware of the additional risk of KSHV morbidity, KSHV+ recipients should not be systematically excluded from kidney transplantation.

Ketosis-prone type 2 diabetes mellitus and human herpesvirus 8 infection in sub-saharan africans.

CONTEXT: An atypical form of type 2 diabetes mellitus (DM-2) is revealed by ketosis (ketosis-prone type 2 diabetes mellitus), frequently occurring in individuals who are black and of African origin, and characterized by an acute onset requiring transient insulin therapy. Its sudden onset suggests precipitating factors. OBJECTIVE: To investigate the putative role of human herpesvirus 8 (HHV-8) in the pathogenesis of ketosis-prone DM-2. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study in which antibodies were searched against latent and lytic HHV-8 antigens using immunofluorescence. The presence of HHV-8 in genomic DNA was investigated in 22 of the participants at clinical onset of diabetes. We also tested whether HHV-8 was able to infect human pancreatic beta cells in culture in vitro. The study was conducted at Saint-Louis University Hospital, Paris, France, from January 2004 to July 2005. All participants were black and of African origin: 187 were consecutive diabetic patients of whom 81 had ketosis-prone DM-2 and 106 had nonketotic DM-2, and 90 individuals were nondiabetic control participants who were matched for age and sex. MAIN OUTCOME MEASURES: Seroprevalence of HHV-8 and percentage of patients with HHV-8 viremia at onset in ketosis-prone DM-2. RESULTS: HHV-8 antibodies were found in 71 patients (87.7%) with ketosis-prone DM-2 vs 16 patients (15.1%) with nonketotic DM-2 (odds ratio, 39.9; 95% confidence interval, 17.1-93.4; P < .001) and 36 of the control participants (40.0%) (odds ratio, 10.7; 95% confidence interval, 4.9-23.4; P < .001). HHV-8 in genomic DNA was present in 6 of 13 patients with ketosis-prone DM-2 tested at acute onset and in 0 of 9 patients with nonketotic DM-2. HHV-8 proteins were present in human islet cells that were cultured for 4 days in the presence of HHV-8. CONCLUSIONS: In this preliminary cross-sectional study, the presence of HHV-8 antibodies was associated with ketosis-prone DM-2 in patients of sub-Saharan African origin. Longitudinal studies are required to understand the clinical significance of these findings.

Idiopathic pulmonary arterial hypertension in Dutch Caucasian patients is not associated with human herpes virus-8 infection.

Samples of lung tissue, taken at time of lung transplant, from 13 Dutch Caucasian patients with idiopathic pulmonary arterial hypertension (iPAH) and 14 patients with non-idiopathic PAH were studied for the presence of human herpes virus-8 (HHV-8). By immunohistochemical staining, in none of patients expression of HHV-8 latency-associated nuclear antigen 1 (LANA-1) was demonstrated. Using two nested polymerase chain reactions (PCR) to amplify part of the open reading frame (ORF) 65 and ORF 73, we failed to detect HHV-8 DNA in all samples studied. These results argue strongly against a role for HHV-8 in the pathogenesis of iPAH.

Serological and molecular evidence that human herpesvirus 8 is endemic among Amerindians in French Guiana.

We evaluated the presence of human herpesvirus 8 (HHV-8) infection among groups of Amerindians in French Guiana. The overall prevalence of antibodies against lytic HHV-8 antigens was 23.0% (180/781), increasing from 18.4% in children <6 years old to approximately 30% in older persons (>45 years). Seroprevalence was higher in Amerindians living in remote localities than it was in those living in the coastal region. Analysis of a 725-base pair fragment of the K1 gene amplified from DNA from a Wayampi Amerindian showed that the virus belonged to molecular subtype E, which has hitherto been found in only a few Amerindians in Brazil and Ecuador.

Increasing seroprevalence of human herpesvirus 8 (HHV-8) with age confirms HHV-8 endemicity in Amazon Amerindians from Brazil.

Human herpesvirus 8 (HHV-8) seroprevalences were determined in two isolated Amazon Amerindian tribes, according to age, gender and familial aggregation. Plasma and serum samples obtained from 982 Amazon Amerindians (664 Tiriyó and 318 Waiampi) were tested for antibodies against lytic and latent HHV-8 antigens by using 'in-house' immunofluorescence assays. Overall, HHV-8 seroprevalence was 56.8 % (57.4 % in the Tiriyó tribe and 55.7 % in the Waiampi tribe). Seroprevalence was independent of gender and increased linearly with age: it was 35.0 % among children aged 2-9 years, 51.4 % in adolescents (10-19 years), 72.9 % in adults and 82.3 % in adults aged >50 years. Interestingly, 44.4 % of children under 2 years of age were HHV-8-seropositive. No significant differences in seroprevalence between tribes and age groups were detected. It is concluded that HHV-8 is hyperendemic in Brazilian Amazon Amerindians, with vertical and horizontal transmission during childhood, familial transmission and sexual contact in adulthood contributing to this high prevalence in these isolated populations.

Human herpesvirus 8 is not associated with sarcoidosis in Japanese patients.

STUDY OBJECTIVES: The etiology of sarcoidosis remains unknown, but recently it was reported that human herpesvirus 8 (HHV-8) may be detected in sarcoid tissue in a high proportion of patients. This study was performed to determine whether HHV-8 is implicated in sarcoidosis in Japan. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from 100 patients with sarcoidosis and 100 healthy donors living in central Japan. Additionally, 19 samples of sarcoid tissue, 10 of tuberculous tissue, and 10 of lung cancers were examined. DNA was extracted from PBMC or tissue samples, and a hemi-nested polymerase chain reaction assay was performed for HHV-8 detection. RESULTS: In the PBMC study, the detection rates for HHV-8 in patients with sarcoidosis and in normal donors were 2% and 1%, respectively, the difference not being significant (p>0.99). In the tissue study, HHV-8 was detected in 10.5% of sarcoid and in 15% of nonsarcoid tissues, again not a significant difference (p>0.99). CONCLUSIONS: From these results, we conclude that HHV-8 is not implicated in sarcoidosis in Japanese patients.

Seroprevalence of human herpesvirus 6 in Andino Puneños (Argentina).

We carried out a seroepidemiological survey to define the prevalence of human herpesvirus 6 (HHV6) infection in an aboriginal population (Andino Puneños) from a remote region in north-west Argentina. Antibodies against HHV6 (total IgG and the 4 subclasses of IgG) were studied in 84 serum samples (collected in 1995 and stored at -70 degrees C), using core blood mononuclear cells infected with HHV6 in an immunofluorescence assay. Of the 84 samples, 70 (83%; 95% confidence interval, 75-91%) exhibited IgG antibodies against HHV6. No significant differences in the frequency of humoral immunity were found among the 4 age-groups studied (mean ages 13, 31, 47 and 70 years) namely, 75%, 89.7%, 79.2% and 100%, respectively. HHV6-specific IgG1 was found in all the positive serum samples tested but none of them contained specific IgG2, IgG3 and IgG4. These results confirmed a high rate of infection with HHV6 within this aboriginal group in Argentina and an IgG1 anti-HHV6 activity compatible with a maintenance of immunity.

Human papillomavirus may be common within nasopharyngeal carcinoma of Caucasian Americans: investigation of Epstein-Barr virus and human papillomavirus in eastern and western nasopharyngeal carcinoma using ligation-dependent polymerase chain reaction.

BACKGROUND: Nasopharyngeal carcinoma (NPC), particularly those tumors endemic to the Far East, commonly harbor Epstein-Barr virus (EBV), thought to serve as an important oncogenic promoter. Human papillomavirus (HPV) is associated with a proportion of upper aerodigestive tract carcinomas. We hypothesized that HPV might also contribute to the pathogenesis of NPC, and we queried whether geographic and racial distinctions may be identified between NPC of the Far East versus those diagnosed in Caucasian American patients with regard to the interrelationship of histologic subtype and viral infection. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissue (FFPET) from 30 patients (6 Caucasian Americans, 1 Chinese American, 14 and 9 patients from Korea and China, respectively) were studied using the ligation-dependent polymerase chain reaction (LD-PCR). These cases were histologically classified according to the World Health Organization (WHO) schema for NPC. Consensus target probes complementary to the L1 region of over 30 HPV types, as well as target probes complementary to EBER-1 (EBV-related nontranslated latency-associated RNA), were used to amplify target sequences. RESULTS: Seven of 30 NPC (23%) contained HPV sequences. There were 6 Caucasian American patients with NPC; 3 cases (50%) were HPV positive (HPV+). Two of these Caucasian Americans had WHO type I tumors: one was HPV+ and EBV negative (EBV-) and the other was HPV-/EBV+. The remaining Caucasian American NPCs were WHO-II/III tumors which tested as follows: two were coinfected with HPV and EBV, the other two contained EBER but not HPV sequences. The single Oriental American patient had a WHO-III NPC which was HPV-/EBV+. Of the Eastern NPC patients, 4 (1 WHO-I, 3 WHO-II/III) of 23 (17%) NPCs contained HPV sequences as well as EBV. Conclusion. Human papillomavirus appears to be uncommonly (17%) associated with NPC in patients from the Far East and was detected more often (50%) in NPC from American Caucasian patients. Some of these tumors conformed to our perceptions and expectations of NPC (eg, WHO-I tumors being EBV-/HPV+ and WHO-III tumors being EBV+/HPV-), but other tumors did not conform to these expectations (eg, WHO-III NPC occasionally harboring both HPV and EBV). There appears to be a broad profile in the relationship between HPV, EBV, and NPC histologic subtype. Unfortunately, the number of American Caucasian cases studied are too small to allow for strong conclusions.

Extranodal head and neck lymphomas in Guatemala: high frequency of Epstein-Barr virus-associated sinonasal lymphomas.

Sinonasal lymphomas of T cell or natural killer cell (T/NK cell) phenotype represent a subset of extranodal head and neck lymphomas. T/NK cell sinonasal lymphomas have been described in diverse geographic settings, including China, Japan, Peru, Northern Europe, and North America. The frequency of these lymphomas is highly dependent on the geographic location in which they occur, their incidence being low in Europe and North America and relatively high in Asian countries and in Peru. Regardless of their geographic location, they are typically associated with the Epstein-Barr virus (EBV). Few studies have addressed the relative frequency of sinonasal lymphoma within the group of extranodal head and neck lymphomas. We investigated the anatomic distribution, immunophenotypical profile, and EBV status of 33 cases of extranodal head and neck lymphoma from patients in Guatemala. The anatomic distribution of these lymphomas is similar to that seen in Asian countries: 17 (52%) in the sinonasal area, five (15%) in the palate, and 11 (33%) in other locations. Fifteen (88%) of the 17 sinonasal lymphomas showed a T or null cell phenotype with a strong association with EBV by in situ hybridization. Most Guatemalan patients with these lymphomas were of Mayan descent. In Guatemala, the relative frequency of sinonasal lymphomas within the group of head and neck lymphomas is significantly higher than that reported for Western countries. In addition, the relative frequency of T/NK versus B cell sinonasal lymphomas is higher than that described in North America and similar to that observed in Asian countries and Peru.

Epstein-Barr virus (EBV) and Hodgkin's disease in a multi-ethnic population in Malaysia.

The Epstein-Barr virus (EBV) has been implicated as a contributing factor in the development of Hodgkin's disease. Western cases of Hodgkin's disease have shown the presence of EBV in Hodgkin and Reed-Sternberg cells in approximately 50%. We studied a total of 100 consecutive cases of Hodgkin's disease from Malaysia, with the aim to elucidate its association with EBV in a multi-ethnic Asian population. Of 34 patients (34%) less than 15 years of age (childhood), 25 had classical Hodgkin's disease (eight nodular sclerosis, 16 mixed cellularity, one lymphocyte depleted) and nine had lymphocyte predominance Hodgkin's disease. Of the 66 from patients aged 15 years and above, 33 had nodular sclerosis, 24 mixed cellularity, two lymphocyte depleted, one unclassifiable and six lymphocyte predominance Hodgkin's disease. The ethnic distribution of classical Hodgkin's disease was: Malay 23, Chinese 32 and Indian 30 (Malay:Chinese:Indian = 1:1.4:1.3), and the ethnic distribution in the 15 cases of lymphocyte predominance Hodgkin's disease was: Malay four, Chinese 10 and Indian one. Taking into account the ethnic distribution of the general population and of hospital admissions, there appears to be a significant predilection of classical Hodgkin's disease cases in ethnic Indian compared to non-Indian patients (chi-squared test, 0.025 > P > 0.01). Eighty-one cases were tested for the presence of EBV by in situ hybridization for EBV encoded RNA, and 57 cases by immunostaining for EBV latent membrane protein 1. In the younger age group, all except one of the 15 cases (nine mixed cellularity, six nodular sclerosis) showed the presence of EBV (93%). In the older age group, EBV was detected (52%) in the following proportion: 6/27 nodular sclerosis, 19/22 mixed cellularity, 1/2 lymphocyte depleted, 1/1 unclassifiable. None of the 14 cases of lymphocyte predominance Hodgkin's disease showed the presence of EBV in the Hodgkin and Reed-Sternberg cells. The findings suggest a strong association of EBV with Hodgkin's disease in Malaysians (41/67, 61%), in particular childhood cases (93%). In adults, the association with EBV is significantly higher in the mixed cellularity subtype (86%) compared with the nodular sclerosis subtype (22%).

[Kikuchi-Fujimoto disease associated with acute infection by herpesvirus 6]. / Enfermedad de Kikuchi-Fujimoto asociada a infección aguda por virus herpes 6.

The histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease is a very rare entity in Spain. We present a 34-year-old arabic male admitted to hospital because one-month story of asthenia, anorexia, weight loss, fever and lymphadenopathies in all palpable sites. Analytic studies were all within normal limits except LDH levels and globular sedimentation rate, both raised. After cervical lymph node biopsy performance high grade Non-Hodgkin lymphoma was initially diagnosed. During admission he complained from pain in both shoulders and an erythematous desquamative eruption in trunk appeared. Some days later, a second lymph node biopsy was performed and Kikuchi-Fujimoto disease was diagnosed. Serologic tests for human herpes virus 6 were positive demonstrating active associated infection. He begun treatment with indomethicin, fever and general symptoms disappeared one week later discontinuing treatment. Two months after discharge, all lymphadenopathies had disappeared. A review on epidemiological, clinical, pathological and differential diagnosis issues is made.

Epstein-Barr virus infection is an early event in gastric carcinogenesis and is independent of bcl-2 expression and p53 accumulation.

Ninety-five cases of adenocarcinoma of the stomach were evaluated for the presence of Epstein-Barr virus (EBV) using a sensitive in situ hybridization assay targeting Epstein-Barr virus-encoded RNA 1 (EBER1) transcripts. EBER1 was detected in 11 of 95 (12%) of cases. When present, the virus was localized to malignant epithelial cells and to dysplastic gastric epithelium, but was not seen in normal-appearing gastric epithelium or intestinal metaplasia. The EBV DNA was monoclonal in all three cases tested by Southern blot analysis of the EBV terminal repeat fragment. These findings suggest that the virus was present before malignant transformation. The presence of EBV was strongly associated with increased numbers of tumor-infiltrating T lymphocytes; however, EBV was not associated with prolonged survival. Neither p53 nor bcl-2 were consistently detected in the EBV-associated tumors. Specifically, 6 of 11 EBV-positive carcinomas had accumulation of p53 protein by immunohistochemical analysis, which was similar to the prevalence of p53 accumulation in EBV-negative specimens and suggests that EBV infection does not substitute for p53 mutations during tumorigenesis. The bcl-2 oncoprotein was expressed in a third of the carcinoma specimens tested, but bcl-2 expression did not correlate with the presence of EBV or with expression of EBV latent membrane protein 1. In conclusion, EBV infection appears to precede malignant transformation in a significant fraction of gastric carcinomas, but neither bcl-2 expression nor p53 accumulation appear to be consistently associated with the presence of the virus.

Undifferentiated carcinoma of the parotid gland in a white patient: detection of Epstein-Barr virus by in situ hybridization.

Paraffin sections of an undifferentiated salivary gland carcinoma of lymphoepithelioma type, arising in a white (Greek) patient and confirmed by immunohistochemistry, were examined for the presence of Epstein-Barr virus (EBV), using in situ hybridization to detect EBV-specific EBER1 message. Epstein-Barr virus was detected in malignant epithelial cells, but was not found in lymphoid stroma or in residual benign salivary epithelium. These results confirm the existence of an association between EBV and tumor cells of undifferentiated carcinoma of parotid gland. This is the first demonstration of EBV in a salivary gland lymphoepithelioma arising in a non-Eskimo, white patient. This finding suggests that the association of EBV with undifferentiated salivary gland carcinoma may exist in geographic regions remote from Greenland.

[Initial studies of the prevalence of human Herpesvirus 7 (HHV-7) in Mexican blood donors]. / Erste Untersuchungen zur Durchseuchung mexikanischer Blutspender mit dem humanen Herpesvirus 7 (HHV-7).

Human herpesvirus 7 (HHV-7) has been recently isolated from CD4-positive peripheral blood lymphocytes of a healthy person. The present study was performed to find the antibody prevalence of this virus in the healthy Mexican population. Two hundred blood samples from candidates for blood donation at the General Hospital of Mexico were studied with the indirect immunofluorescence test (IFA) in HHV-7 infected SupT1 cells. 83.5% were male persons and 16.5% female, the mean age for the male group was 28.8 years and for the female group 31.5. The donors came from 12 different states in Mexico, predominantly from the city (60.8%), and had different occupations. Almost all samples (98.5%) were positive to HHV-7. Other studies done revealed 1% positive to brucella, 1% positive to Hepatitis B, 2% positive to syphilis, hepatitis C and HIV test were negative in the whole group studied. There was a high incidence of HHV-7 in the group studied: more than 50% of the subject had high titers. This results should be further studied determine titers indicative of an active infection and to search for any association with illnesses.