Presence Of Human Herpesvirus 8 Research Articles

The Emergence of HHV-8 Infection among HIV-positive Individuals Residing in Bali, Indonesia

Background:
 Human herpesvirus 8 (HHV-8) is considered as the etiological agent of Kaposi’s sarcoma (KS). In people living with human immunodeficiency virus (HIV) (PLHIV), KS defines acquired immunodeficiency syndrome (AIDS). Previous study found that HIV-positive individuals were more likely to be HHV-8 seropositive than HIV-negative individuals. Reports regarding the presence of HHV-8 and HIV co-infection in Indonesia is severely limited. 
 Aim:
 This study aimed to identify HHV-8 infection among HIV-positive individuals in Bali, Indonesia.
 Materials and Methods:
 Forty three plasma samples were collected from 16 antiretroviral therapy (ART) naive and 27 ART-experienced individuals residing in Buleleng Regency, Bali, Indonesia. Detection of HHV-8 antigen was performed by using ELISA method. The Fisher's Exact test and the Spearman correlation test would be used to analysed data accordingly.
 Results:
 Seven samples (7/43, 16.3%), one of ART-naive individual (1/16, 6.25%) and six of ART-experienced individuals (6/27, 22.2%), were tested positive for HHV-8 antigen. Human herpesvirus 8 infection was correlated neither to sex (p=1.000) and age (p=0.716), nor to ART status (p=0.178) and length of ART (p=0.465).
 Conclusion:
 This study indicates the emergence of HHV-8 infection among HIV-positive individuals residing in Bali, Indonesia. Sufficient diagnosis of HHV-8 should be considered for all HIV-positive individuals in order to deliver appropriate treatment. Extensive researches is suggested to be conducted in more regions of Indonesia in order to determine the magnitude of HHV-8 infection among HIV-positive individuals.

γ-Interferon Produced by CD8+ T Cells Infiltrating Kaposi's Sarcoma Induces Spindle Cells With Angiogenic Phenotype and Synergy With Human Immunodeficiency Virus-1 Tat Protein: An Immune Response to Human Herpesvirus-8 Infection?

AbstractKaposi's sarcoma (KS) is an angioproliferative disease associated with infection by the human herpesvirus-8 (HHV-8). HHV-8 possesses genes including homologs of interleukin-8 (IL-8) receptor, Bcl-2, and cyclin D, which can potentially transform the host cell. However, the expression of these genes in KS tissues is very low or undetectable and HHV-8 does not seem to transform human cells in vitro. In addition, KS may not be a true cancer at least in the early stage. This indicated that besides its transforming potential, HHV-8 may act in KS pathogenesis also through indirect mechanisms. Evidence suggests that KS may start as an inflammatory-angiogenic lesion mediated by cytokines. However, little is known on the nature of the inflammatory cell infiltration present in KS, on the type of cytokines produced and on their role in KS, and whether this correlates with the presence of HHV-8. Here we show that both acquired immunodeficiency syndrome (AIDS)-KS and classical KS (C-KS) lesions are infiltrated by CD8+ T cells and CD14+/CD68+monocytes-macrophages producing high levels of γ-interferon (γIFN) which, in turn, promotes the formation of KS spindle cells with angiogenic phenotype. γIFN, in fact, induces endothelial cells to acquire the same features of KS cells, including the spindle morphology and the pattern of cell marker expression. In addition, endothelial cells activated by γIFN induce angiogenic lesions in nude mice closely resembling early KS. These KS-like lesions are accompanied by production of basic fibroblast growth factor, an angiogenic factor highly expressed in primary lesions that mediates angiogenesis and spindle cell growth. The formation of KS-like lesions is upregulated by the human immunodeficiency virus Tat protein demonstrating its role as a progression factor in AIDS-KS. Finally, γIFN and HLA-DR expression correlate with the presence of HHV-8 in lesional and uninvolved tissues from the same patients. As HHV-8 infects both mononuclear cells infiltrating KS lesions and KS spindle cells, these results suggest that HHV-8 may elicit or participate in a local immune response characterized by infiltration of CD8+ T cells and intense production of γIFN which, in turn, plays a key role in KS development.

Prevalence of Human Herpes Virus 8 Infection and Pattern of TLR4 rs4986791 Polymorphism in Women with Breast Cancer

Background: Breast cancer is a major cause of female death worldwide. Several factors contribute to cancer development, one of the most important of which is viruses identified by the host immune system and Toll-like receptors (TLRs). Human herpes virus 8 (HHV-8) is one of the viruses with a proven role in Kaposi’s sarcoma development. Objectives: This study aimed to investigate the correlation between HHV-8 infection and breast cancer, as well as the role of rs4986791 polymorphism in women’s health. Methods: Blood samples of 80 healthy subjects and 80 patients suffering from breast cancer were collected (from May-September 2018). The presence of HHV-8 in the samples was examined by PCR. Also, the rs4986791 polymorphism was evaluated by nested PCR-RFLP. Results: The results showed a significant relationship between age and breast cancer. Of 80 cancer patients and 80 healthy subjects, 17 (21.3%) and 15 (18.8%) were carriers of HHV-8, respectively. Also, there was no significant relationship between HHV-8 infection and breast cancer (P = 0.693). We found no significant relationship between the presence of virus and cancer grade (P = 0.618). Conclusions: The results of rs498679 polymorphism analysis indicated that the T allele was associated with increased health phenotype and decreased risk of cancer development. Also, women with TT genotype exhibited significantly lower HHV-8 infection than the other genotypes.

Human 8–Associated Intravascular Lymphomatosis Within an AIDS Patient

Human herpesvirus 8 (HHV-8) causes Kaposi sarcoma (KS) and is associated with B-cell malignancies. Intravascular large B-cell lymphoma is an uncommon B-cell lymphoma characterized by proliferation of neoplastic B cells within the lumina of blood vessels. Although the underlying cause of this lymphoma is unclear, a previous report has identified a single case of HHV-8–associated intravascular lymphomatosis (IVL). We analyzed 5 cases of IVL for the presence of HHV-8, finding the second case of HHV-8–associated IVL. Human herpesvirus 8 protein expression (latency-associated nuclear antigen 1 [LANA-1]), Epstein-Barr virus–encoded RNAs (EBERs), and the cellular markers CD20 and CD45 were determined by immunohistochemistry. Intravascular lymphoma cells from a subject with human immunodeficiency virus (HIV) were positive for HHV-8 LANA-1, EBV EBER, and CD20 and CD45 expression. The 4 non-HIV–infected IVL cases were negative for HHV-8 LANA-1 and EBER expression. Future studies are required to determine whether the association between HHV-8 and HIV with IVL is true.

Successful Treatment of Iatrogenic Multicentric Castleman’s Disease Arising Due to Recrudescence of HHV-8 in a Liver Transplant Patient

We describe the case of a 59-year-old HIV-negative male who developed multicentric Castleman's disease (MCD) 1 year postliver transplantation due to recrudescence of a pretransplant human herpesvirus-8 (HHV-8) infection. He presented with fevers, dry cough, weight loss and drenching night sweats. Routine investigations were all unremarkable. Computerized axial tomography (CT) scans showed splenomegaly and intra-abdominal lymphadenopathy, confirmed by positron emission tomography. Cervical lymph node biopsies were consistent with MCD. The presence of HHV-8 was confirmed on immunohistochemistry. Peripheral blood HHV-8 quantitative polymerase chain reaction (qPCR) monitoring showed a threefold decrease in viremia in the first week of treatment with ganciclovir but had little impact on clinical symptoms. Reducing immunosuppression and switching to rituximab resolved clinical symptoms and produced a negative HHV-8 qPCR result. Retrospective molecular testing of sera collected pre- and immediately posttransplantation confirmed preexisting HHV-8 in the host. This is the first reported case of an HIV-negative postliver transplant patient developing MCD that manifested as posttransplant lymphoproliferative disorder due to recrudescence of HHV-8. We propose (1) the introduction of the term iatrogenic Castleman's disease (CD) for this and similar cases, (2) rituximab should be considered as a treatment option for CD and (3) consideration be given to a change to the World Health Organization classification of CD to incorporate such cases.

Human herpes virus-8 in human immunodefi ciency virus/ acquired immunodefi ciency syndrome - associated oral Kaposi’s sarcoma

Human herpes virus-8 (HHV-8), now called Kaposi’s sarcoma-associated herpes virus (KSHV), as a probable causative agent of Kaposi’s sarcoma (KS) was putforth when it was first detected in KS specimens in 1994. Since then, many investigators have confirmed the association of HHV-8 and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) - associated KS. This study was done to review the original research aimed at assessing the presence of HHV-8 in HIV/AIDSassociated oral KS and other oral lesions.

One hundred and five Kaposi sarcoma patients: a clinical study in Xinjiang, Northwest of China

Kaposi's sarcoma (KS) is an unusual illness that may be associated with human herpes virus 8 (HHV-8) infections, and appears mainly in Jews, Italians and Greeks. There is a lack of patient data in Xinjiang regarding the clinical characteristics of KS. To review the clinical characteristics of a series of patients with KS in Xinjiang, Northwest China, over 16-year period. A retrospective analysis of patients referred to a Xinjiang hospital in Northwest China with classic KS (CKS) and AIDS-associated KS (AIDS-KS) between January 1997 and April 2013 was performed. Reviewed information included demographics, clinical features, histopathological traits, treatment and presence of HHV-8 infection. During the study period, 105 patients with a diagnosis of KS, including 77 CKS and 28 AIDS-KS, were referred to our hospital. Mean age at diagnosis was 55.8±16.8years (range: 25-85years). There were 70 (90.9%) males and 7 (9.1%) females (male-to-female ratio: 10:1) having CKS and 21 (75.0%) males and 7 (25.0%) females (male-to-female ratio: 3:1) with AIDS-KS. Most of the patients were Uyghur, including 67 CKS and 24 AIDS-KS. The rate of multifocal lesions at diagnosis was 98.1% (103/105). The most common area of lesions was between 1% and 5% of CKS and AIDS-KS. The main types of lesions were nodules, patches and plaques. The lower extremity and foot were the most common locations for CKS and AIDS-KS. In addition to skin damage, the penis, mouth, lymph nodes and interstitial lung tissues were involved in some cases. No second primary malignancy was diagnosed. Systemic chemotherapy and radiotherapy were effective treatments for CKS. The HHV-8 positivity rate was 98.98% in 98 KS cases. In Xinjiang, most CKS and AIDS-KS patients were older Uyghur men. AIDS-KS was found predominantly among 30-year-old Uyghur patients, compared with 60years for those having CKS. The latter exhibited certain characteristics such as disseminated skin disease; in some patients, the condition was accompanied by lymphedema, visceral or lymph node involvement, but no secondary malignancies. In addition, the HHV-8 positivity rate associated with KS was very high.

Measurements of human herpesvirus 8 viral load in blood before and after leukoreduction filtration

Human herpesvirus 8 (HHV-8) is likely transmitted through blood transfusion in high-prevalence areas. The efficacy of leukoreduction filtration for reducing HHV-8 in blood has not been reported. Blood was drawn from 45 human immunodeficiency virus-positive men either with Kaposi's sarcoma (KS; n=21) or without KS (n=24) and subject to leukoreduction filtration. HHV-8 viral load was measured in plasma and in blood before and after filtration. Twelve subjects, all with KS, had detectable HHV-8 viremia before filtration with viral loads of 10(2) to 10(5) copies/mL (mean, 3 × 10(4) copies/mL). After filtration, seven of 12 subjects no longer had detectable HHV-8 in their blood, and five of 12 subjects had detectable HHV-8 that was 90% reduced on average from prefiltration levels. The presence of HHV-8 in the blood after filtration was strongly associated with prefiltration viral loads greater than 1000 copies/mL and the presence of cell-free virus in plasma. None of the subjects without KS had detectable levels of HHV-8 virus in blood before or after filtration. Cell-associated HHV-8 appeared to be effectively removed by leukoreduction filtration. Cell-free HHV-8 was present in 42% of subjects as 1% to 20% of the total virus which was not removed by filtration.

Corticosteroid induced, HHV-8 positive Kaposi’s sarcoma in a non-HIV elderly patient

Kaposi’s sarcoma (KS) was first described in 1872 by Moritz Kaposi. In 1994, Chang et al. first identified DNA sequences corresponding to human herpesvirus-8 (HHV-8) in AIDS-associated Kaposi sarcoma biopsies. It is now believed that presence of HHV-8 is necessary but not sufficient to cause KS. Other factors like immunosuppressive therapy also play a role. We describe an HIV-negative elderly patient who developed KS of skin and mucous membrane after prolonged use of corticosteroids for knee pain. The patient was positive for HHV-8.

Human γ-Herpesviruses Epstein-Barr Virus and Human Herpesvirus-8 Are Not Detected in the Lungs of Patients With Severe Pulmonary Arterial Hypertension

In susceptible individuals, multiple events may trigger pulmonary vascular remodeling and pulmonary arterial hypertension (PAH). Human herpesvirus-8 (HHV-8), a γ-herpesvirus homologous with Epstein-Barr virus (EBV), was suggested to act as a "second hit" in the development of PAH in susceptible patients. Although there is indirect evidence from in vitro and animal studies in favor of a link between γ-herpesviruses and the pathophysiology of PAH, results remain controversial. Therefore, we investigated the presence of EBV and HHV-8 in the lungs of patients with PAH. Thirty-four lungs explanted from French patients with end-stage PAH (mean age, 38 ± 14 years; 19 women) were studied. Tissue samples were incorporated into tissue microarrays. Normal lung tissues served as negative controls. Kaposi sarcoma tissue served as a positive control for HHV-8, and EBV-associated lymphoma served as a positive control for EBV. The presence of HHV-8 was investigated with immunohistochemistry and polymerase chain reaction. The presence of EBV was investigated with immunohistochemistry and in situ hybridization. For HHV-8, none of PAH lung samples showed a "stippling" nuclear pattern classically observed in HHV-8-positive Kaposi sarcoma lesions. When studied by polymerase chain reaction, all cases remained negative. For EBV, none of the PAH lung samples showed positive staining, whatever the technique applied. HHV-8 and EBV cannot be detected in the lungs of patients with end-stage PAH. The role of these γ-herpesviruses in the pathophysiology of PAH is, therefore, unlikely.

Frequent detection of Human Herpes Virus-8 in bone marrow of Jordanian patients of multiple myeloma

The association between Human Herpes Virus-8 (HHV-8), also called Kaposi's sarcoma associated herpesvirus (KSHV), and the pathogenesis of multiple myeloma remains controversial. Many past studies conducting on different populations have come to contradicting conclusions. In this study, we attempted to investigate the presence of HHV-8 in Jordanian multiple myeloma patients. We carried out nucleic acid amplification reactions targeting specific viral DNA sequences on 35 fresh bone marrow aspirate samples from 17 patients with multiple myeloma, 9 patients with various hematological malignancies and 9 normal subjects. HHV-8 specific sequences were detected in 7 out of 17 multiple myeloma patients (41%) using primers specific for the open reading frame region 26 (ORF26). All patients with other hematological malignancies as well as the normal subjects did not harbour the virus. These findings support the previous reports of frequent detection of HHV-8 in bone marrow of multiple myeloma patients.

Pemphigus vulgaris and herpesviruses: is there any relationship?

Pemphigus is an autoimmune disorder, which results from interaction of exogenous and endogenous factors. One of these environmental factors is viral infections particularly, herpesviruses. We aimed to detect the presence of HSV 1 and 2 (herpes simplex virus) and HHV8 (human herpesvirus 8) in our patients who were suffering from pemphigus vulgaris. In this cross-sectional study, 38 patients (19 male and 19 female patients) with pemphigus vulgaris were entered, 32 skins and six peripheral blood cells samples were obtained from the study population. Thereafter, the presence of HHV8 and HSV DNA were evaluated by using polymerase chain reaction (PCR). The mean age of patients was 45.05 ± 17.24 years (range: 16-81 years). Twelve patients mentioned history of herpes labial in the past (31.57%). Results of PCR test for detection of HSV and HHV8 DNA in all 32 skin samples and five peripheral blood samples and one case with skin and blood samples were reported negative. Inability to detect HHV8 and HSV DNA in this study suggests that herpesviruses may be only occasional factors for development or exacerbation of pemphigus vulgaris.

Human Herpesvirus 8 DNA Load in the Leukocytes Correlates with the Platelet Counts in HIV Type 1-Infected Individuals

Abstract Human herpes virus 8 (HHV-8) is known to be reactivated in immunocompromised situations and it is associated with Kaposi's sarcoma (KS) and some hematological diseases. The aim of this study was to analyze the effect of HHV-8 on HIV-1 infection, especially on thrombocytopenia complicated with HIV infection. The HHV-8 DNA load was determined by a quantitative real-time PCR, using leukocytes from 125 HIV-1-infected individuals. HHV-8 DNA was detected in 37 individuals. The increased HIV-1 load and reduced percentage of CD4-positive T cells were significantly associated with the presence of HHV-8. The prevalence and load for HHV-8 are higher in patients with KS than in patients without KS, but the difference is not significant. The increased HHV-8 DNA load was significantly correlated with thrombocytopenia, and platelet counts were significantly lower in individuals with HHV-8 than in individuals without HHV-8. We also obtained the negative correlations between changes in platelet counts and changes in HHV-8 DNA loads. The association between thrombocytopenia and HHV-8 has never been reported previously, apart from some case reports of Castleman's disease and KS. Various cytokines or chemokines are produced by HHV-8-infected cells, some of which have been reported to inhibit hematopoiesis. This may be one of the mechanisms by which HHV-8 infection induces thrombocytopenia. These results indicate that HHV-8 DNA in leukocytes may provide useful information for the assessment of the clinical appearance of HIV-1 infection.

Complete regression of HIV-associated multicentric Castleman disease treated with rituximab and thalidomide

Complete regression of HIV-associated multicentric Castleman disease treated with rituximab and thalidomide

Ketosis-Prone Type 2 Diabetes Mellitus and <emph type="ital">Human Herpesvirus 8</emph> Infection in Sub-Saharan Africans

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. To investigate the putative role of human herpesvirus 8 (HHV-8) in the pathogenesis of ketosis-prone DM-2. 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. Seroprevalence of HHV-8 and percentage of patients with HHV-8 viremia at onset in ketosis-prone DM-2. 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. 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.

Sarcoma de Kaposi asociado a corticoterapia sistémica

Kaposi sarcoma (KS) was first described in 1872 by Moritz Kaposi. Its epidemiology is suggestive of an infectious disease and in 1994 Chang and coworkers identified DNA sequences corresponding to a previously unidentified herpes virus—human herpes virus 8 (HHV-8)—in AIDS-associated KS biopsies. It is now believed that the presence of HHV-8 is a necessary condition but not sufficient on its own to cause KS. Other factors such as immunosuppression should also be considered and it is known that immunosuppressive therapy increases the risk of KS. We describe a patient who developed KS after prolonged prednisone therapy for temporal arteritis.

Intestinal Kaposi’s sarcoma may mimic gastrointestinal stromal tumor in HIV infection

Diffuse intestinal Kaposi's sarcoma shares macroscopic and histopathologic features with gastrointestinal stromal tumors. Correct diagnosis may pose a clinical challenge. We describe the case of a young HIV-1-infected African lady without advanced immunodeficiency, who presented with a diffuse spindle cell tumor of the gut. Initial diagnosis was of a gastrointestinal stromal tumor, based on endoscopy and histopathology. Further evaluation revealed evidence for human herpesvirus 8 (HHV8) and the diagnosis had to be changed to diffuse intestinal Kaposi's sarcoma. Antiretroviral triple therapy together with chemotherapy was commenced, and has led to the rapid remission of intestinal lesions. With a background of HIV infection, the presence of HHV8 as the causative agent of Kaposi's sarcoma should be determined, as distinct treatment is indicated.

Kaposi Sarcoma Associated With Systemic Corticosteroid Therapy

Kaposi sarcoma (KS) was first described in 1872 by Moritz Kaposi. Its epidemiology is suggestive of an infectious disease and in 1994 Chang and coworkers identified DNA sequences corresponding to a previously unidentified herpes virus—human herpes virus 8 (HHV-8)—in AIDS-associated KS biopsies. It is now believed that the presence of HHV-8 is a necessary condition but not sufficient on its own to cause KS. Other factors such as immunosuppression should also be considered and it is known that immunosuppressive therapy increases the risk of KS. We describe a patient who developed KS after prolonged prednisone therapy for temporal arteritis.

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.

IS CLASSIC KAPOSI’S SARCOMA ENDEMIC IN PERU?: REPORT OF A CASE IN AN INDIGENOUS PATIENT

Kaposi's sarcoma (KS) has been classified in four clinical variants (classic or Mediterranean; endemic or African; epidemic or AIDS-related; iatrogenic or immunosuppression-related). Human herpesvirus 8 (HHV-8), has been found in all these variants. We herein discuss the unusual presentation of a 53-year-old indigenous patient with purplish-brown nodular lesions on lower extremities, and miliary tuberculosis. ELISA-HIV tests were negative and immunohistochemistry (IHC) of the tumor tissue was positive for HHV-8. This is the first reported case in which the presence of HHV-8 was evidenced by means of IHC techniques in Peru. We also review all available Peruvian literature of classic KS, a disease that has been frequently reported in indigenous population of Peru since 1968, making this country a possible endemic zone of classic KS.