Murine gammaherpesvirus 68 (MHV-68), a member of the gammaherpesvirus family, replicates robustly in permissive cell lines and is able to infect laboratory mice. MHV-68 has emerged as a model for studying the basic aspects of viral replication and host-virus interactions of its human counterparts. Herpesvirus genome replication is mediated through a cis-element in the viral genome called the origin of lytic replication (oriLyt). A family of transcription factors, CCAAT/enhancer binding proteins (C/EBPs), assists in oriLyt-mediated DNA replication during gammaherpesvirus reactivation. In this study, we examined the role of C/EBPs in gammaherpesvirus DNA replication during de novo infection, using MHV-68 as a model. We found that C/EBP α and β bind to the CCAAT boxes in the MHV-68 oriLyt core region both in vitro and in vivo, as demonstrated by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. A dominant negative form of C/EBPs significantly impaired the lytic replication efficiency of MHV-68 on both the plasmid and genome levels in a replication assay, indicating that functional C/EBPs are required for maximal MHV-68 genome DNA replication. Collectively, our data demonstrate that C/EBPs interact with the oriLyt core region and play an important role in MHV-68 lytic DNA replication during de novo infection.
Animals ; Base Sequence ; CCAAT-Enhancer-Binding Proteins ; genetics ; metabolism ; Cell Line ; Chromatin Immunoprecipitation ; Cricetinae ; DNA Replication ; DNA, Viral ; chemistry ; genetics ; metabolism ; Electrophoretic Mobility Shift Assay ; Genome, Viral ; Herpesviridae Infections ; genetics ; metabolism ; virology ; Humans ; Mice ; Molecular Sequence Data ; Plasmids ; Promoter Regions, Genetic ; Protein Isoforms ; genetics ; metabolism ; Replication Origin ; Rhadinovirus ; genetics ; metabolism ; Viral Proteins ; genetics ; metabolism ; Virus Latency ; genetics

No abstract available.
Herpesviridae* ; Herpesvirus 7, Human ; Herpesvirus 8, Human ; Humans*

No abstract available.
Biopsy* ; Herpesvirus 8, Human ; Sarcoma, Kaposi*

Castleman's disease (CD) is a rare lymphoproliferative disorder that comprises at least two distinct clinical subtypes (unicentric and multicentric). Three pathologic variants (hyaline vascular variant, plasma cell variant, and mixed variant) have been recognized. In addition to interleukin-6 and human herpes virus 8, some other cytokines and viruses may also be involved in the pathogenesis of CD. This review summarizes the recent advances in the underlying pathogenesis of CD, with an attempt to provide evidence for new treatment options that may change the current treatment strategies and improve patients' outcomes.
Castleman Disease ; Herpesvirus 8, Human ; Humans ; Interleukin-6

No abstract available.
Herpesvirus 8, Human* ; Humans* ; Kidney Transplantation ; Lymphohistiocytosis, Hemophagocytic* ; Sarcoma, Kaposi* ; Transplant Recipients*

BACKGROUND: The differential diagnosis of Kaposi sarcoma includes many disease that range from benign disease to malignant tumors. However, little information is available about the immunohistochemical characteristics of Kaposi sarcoma. METHODS: The expressions of 13 various proteins (HHV-8 LNA-1, Ki-67, bcl-2, p53, CD31, CD34, factor VIII, D2-40, vimentin, SMA, S-100, EMA, and c-kit) were evaluated immunohistochemically in 49 vascular tumors including 16 Kaposi sarcomas, 8 angiosarcomas, 2 hemangioendotheliomas, and 23 benign vascular tumors with using the tissue array method. RESULTS: All 16 cases of Kaposi sarcoma showed nuclear staining for HHV-8 LNA-1, whereas all the cases of angiosarcoma and benign vascular lesions were negative for HHV-8 LNA-1 (p<0.001). All Kaposi sarcoma were positive for D2-40, which is a marker of lymphatic differentiation, but 25% of the benign vascular lesions and 30.4% of the angiosarcoma were positive for D2-40 (p<0.001). The mean proliferation index as assessed by Ki-67 immunostaining revealed no difference between the benign and malignant vascular lesions (p>0.05). No Kaposi sarcoma showed a bcl-2 expression, but 62.5% of the angiosarcomas and 21.7% of the benign vascular tumors had bcl-2 expressions (p=0.005). CONCLUSIONS: Immunohistochemical detection of HHV-8 LNA-1 and D2-40 are useful tools to differentiate Kaposi sarcoma from other vascular tumors.
Diagnosis, Differential ; Factor VIII ; Hemangioendothelioma ; Hemangiosarcoma ; Herpesvirus 8, Human ; Immunohistochemistry ; Sarcoma, Kaposi* ; Vimentin

Castleman's disease is a rare atypical lymphoproliferative disorder. Although HHV-8 has been reported to be a cause of Castleman's disease, the etiology and pathogenesis of the disease remains mostly unknown. We experienced a 51-year-old female patient who was concurrently diagnosed with Castleman's disease and systemic lupus erythematosus. Castleman's disease has been rarely reported in patients with systemic lupus erythematosus. Thus, we report the case and briefly discuss relevant articles.
Female ; Giant Lymph Node Hyperplasia ; Herpesvirus 8, Human ; Humans ; Lupus Erythematosus, Systemic ; Lymphoproliferative Disorders

Kaposi's sarcoma(KS) occurs in four distinct subsets: classic, African-endemic, iatrogenic immunosuppressive drug-associated, and AIDS-associated KS. Only two cases of AIDS-associated KS have been reported in Korea. The pathogenesis remains unclear but, suggested the relevance to the association of virus infection with KS, especially human herpesvirus-8. We report a case of an AIDS-related KS that human herpesvirus-8 DNA is present in the KS tissue. The patient was diagnosed with AIDS in 1993 and had complained of disseminated erythematous to purplish colored papulonodules on the face, neck, chest and back for 5months. He was treated with systemic cytotoxic chemotherapy, but died due to septic condition.
DNA ; Drug Therapy ; Herpesvirus 8, Human ; Humans ; Korea ; Neck ; Sarcoma, Kaposi* ; Thorax

Castleman's disease (CD) is a rare lymphoproliferative disorder. The etiology of CD may involve viral infection, abnormal modulation of cytokines, and angiogenesis. Human herpes virus (HHV) -8 infection and interleukin-6 (IL-6) overexpression may play key roles in the development of CD. Treatment options include surgical excision, radiation therapy, chemotherapy, antiviral therapy, and targeted therapy. No standardized treatment has been established for multicentric CD and the treatment efficacy usually is poor. Among newly available agents, the effectiveness of antiviral therapy against HHV-8 is unclear; anti-CD20 and anti-IL-6 receptor monoclonal antibodies have shown promising efficacy; thalidomide and bortezomib have shown their initial efficacy.
Castleman Disease ; etiology ; metabolism ; therapy ; Herpesvirus 8, Human ; Humans ; Interleukin-6 ; metabolism

Self-regression of Kaposi's sarcoma is rare with the exception of the iatrogenic immunosuppressive type. No cases of classic type Kaposi's sarcoma showing spontaneous regression have been reported in the Korean dermatologic literature. We report a case of classic type of Kaposi's sarcoma in a 69-year-old man which followed a clinical course of spontaneous regression. He presented with multiple asymptomatic beefy red papules and nodules scattered on both cheeks and upper extremities during a state of increase in the number of skin lesions at the initial visit. He had no history of immunosuppressive treatment and the laboratory findings were unremarkable. An anti-HIV antibody test was negative. A histopathologic examination revealed typical findings of Kaposi's sarcoma and positive staining with CD31 and D2-40. HHV-8 DNA was detected in a biopsy specimen. Without any specific treatment, the skin lesions healed without leaving any complications after 15 months, and did not show any evidence of recurrence during the ensuing 5 years.
Aged ; Biopsy ; Cheek ; DNA ; Herpesvirus 8, Human ; Humans ; Recurrence ; Sarcoma, Kaposi ; Skin ; Upper Extremity