p53

Scheda a cura di Marco Chilosi (GYM)

MICROORGANISMI : HHV8

BIBLIOGRAFIA

Virology. 2000 Apr 10;269(2):335-44.

Expression and localization of human herpesvirus 8-encoded proteins in primary effusion lymphoma, Kaposi's sarcoma, and multicentric Castleman's disease.

Katano H, Sato Y, Kurata T, Mori S, Sata T.

Department of Pathology, National Institute of Infectious Diseases, University of Tokyo, Japan.

To investigate the expression of human herpesvirus 8 (HHV8)-encoded proteins in the cells of primary effusion lymphoma (PEL), Kaposi's sarcoma (KS) and multicentric Castleman's disease (MCD), nine rabbit polyclonal antibodies to K2, ORF26, K8, K8.1, K10, K11, ORF59, ORF65, and ORF73 were developed. Western blot analysis in PEL cell lines (TY-1 and BCBL-1) revealed that the expression of these proteins, except ORF73 (LANA), was induced by tetradecanoylphorbol acetate (TPA) treatment, indicating that these proteins are lytic proteins. Immunofluorescence assay in primary PEL cells derived from pericardial effusion and PEL cell lines with and without TPA treatment revealed that primary PEL cells exhibited the same expression pattern as noninduced PEL cell lines, and the treatment changed localization of K8, ORF59, and ORF65 proteins. Immunohistochemistry revealed that 90% of KS spindle cells expressed the ORF73 protein, whereas a small population of KS cells expressed K8, K10, K11, ORF59, and ORF65 proteins. In MCD, ORF73, ORF59, K8, K2, and K10 proteins were expressed in the cells at mantle zone of the follicle. These data indicate that KS and PEL cells expressed predominantly latent proteins, whereas MCD expressed both latent and lytic proteins, suggesting that HHV8 plays a different role in the pathogenesis of HHV8-associated diseases.

Localization of human herpes-like virus type 8 in vascular endothelial cells and perivascular spindle-shaped cells of Kaposi's sarcoma lesions by in situ hybridization.

Li JJ, Huang YQ, Cockerell CJ, Friedman-Kien AE.

Department of Dermatology, New York University Medical Center, New York, New York 10016, USA.

Kaposi's sarcoma (KS) is a neoplasm that develops as multifocal lesions characterized by a histological picture that includes irregularly shaped vascular spaces surrounded by perivascular and interstitial spindle-shaped cells, extravasated erythrocytes, and an inflammatory mononuclear cell infiltrate. Recently, the DNA sequences of a novel human gamma-herpesvirus-like (HHV-8) agent have been detected by polymerase chain reaction in KS associated with acquired immune deficiency syndrome (AIDS-KS), classical KS, and African endemic KS. The present study was done to identify the specific cells within KS tumors that contain the viral DNA. Fourteen skin biopsy specimens, including three classical KSs, six AIDS-KSs, three normal skin specimens, and two common warts from healthy individuals, were examined by polymerase chain reaction for the presence of the HHV-8 DNA sequences. HHV-8 DNA were present in all nine KS specimens but not detectable in the five non-KS tissue samples. Using in situ hybridization, we found the HHV-8 DNA sequences to be predominantly localized to the nuclei of endothelial cells lining the vascular slits and some perivascular spindle-shaped cells, in two of three KS and four of six AIDS-KS tissue sections examined. The HHV-8-positive cells of KS specimens were concurrently shown to also be positive for factor-VIII-related antigen by immunohistochemical staining. The presence of the DNA of HHV-8 in the nuclei of KS cells further supports the possibility that this agent may play a role in the pathogenesis of this tumor.

Nat Med. 1995 Dec;1(12):1274-8.

Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells.

Boshoff C, Schulz TF, Kennedy MM, Graham AK, Fisher C, Thomas A, McGee JO, Weiss RA, O'Leary JJ.

Virology Laboratory, Royal Marsden Hospital, London, UK.

Kaposi's sarcoma (KS), a vascular tumour that contains characteristic spindle cells forming slit-like spaces, may have an infectious aetiology. Recently, sequences of a new human herpesvirus, KSHV/HHV-8, have been identified in both HIV-associated and classical KS. We sought to identify the target cell of this virus in KS tumour tissue. Using PCR in situ hybridization (PCR-ISH) we show that KSHV/HHV-8 is present in the flat endothelial cells lining vascular spaces of KS lesions as well as in typical KS spindle cells. These findings show that KSHV/HHV-8 is present in the cell types thought to represent neoplastic cells in these lesions.

Am J Clin Pathol. 2002 Feb;117(2):268-75.

Analysis of the human herpesvirus 8 (HHV-8) genome and HHV-8 vIL-6 expression in archival cases of castleman disease at low risk for HIV infection.

Menke DM, Chadbum A, Cesarman E, Green E, Berenson J, Said J, Tiemann M, Parwaresch R, Thome SD.

Department of Pathology, Mayo Clinic, Jacksonville, FL 32224, USA.

Lymph nodes from 44 patients with Castleman disease (CD) without risk factors for HIV infection were analyzed with polymerase chain reaction (PCR), in situ hybridization (ISH), and immunohistochemical analysis for human herpesvirus 8 (HHV-8) and viral interleukin-6 (vIL-6). PCR detected HHV-8 genome in 2 of 4 cases; ISH detected it in 9 of 16 cases. HHV-8 vIL-6 peptides were detected in 2 of 44 cases. vIL-6- and ISH-positive cells were found in large transformed and small lymphocytes of the follicular mantle, respectively. Of 9 cases of plasma cell (PC) CD that demonstrated HHV-8 genome by PCR or ISH, 1 expressed vIL-6. Clonal populations of PCs in CD by immunohistochemical analysis or immunoelectrophoresis of serum and urine were associated with neuropathy. HHV-8 vIL-6 detection was associated with poor survival and lack of HHV-8 IL-6, with low risk for subsequent lymphoma. Although HHV-8 genome was detected in a considerable number of patients with PC CD, vIL-6 expression was infrequent. Expression of HHV-8 vIL-6 in CD may indicate poor prognosis in patients at risk for lymphoma who may prospectively require more aggressive treatment. The lack of vIL-6 expression in CD with HHV-8 genome suggests that human IL-6 rather than vIL-6 may be the principal pathogenic cytokine.

Am J Surg Pathol. 1999 Nov;23(11):1393-400.

Posttransplantation plasmacytic proliferations related to Kaposi's sarcoma-associated herpesvirus. Matsushima AY, Strauchen JA, Lee G, Scigliano E, Hale EE, Weisse MT, Burstein D, Kamel O, Moore PS, Chang Y.

Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

Kaposi's sarcoma-associated herpesvirus (KSHV), which was originally detected in Kaposi's sarcoma, also has been found in primary effusion lymphomas (PELs) and some cases of multicentric Castleman's disease. We describe two transplant recipients who developed Kaposi's sarcoma and a spectrum of non-neoplastic lymphoproliferative disorders that show pronounced plasmacytic and plasmacytoid features. The first patient had recurrent pleural effusions and Castleman's disease-like changes in lymph nodes. The second patient had systemic lymphadenopathy and hepatosplenomegaly secondary to diffuse infiltration by polyclonal plasma cells and plasmacytoid B lymphocytes that clinically mimicked Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease. In both cases, KSHV DNA was detected by polymerase chain reaction and Southern blotting, and KSHV vIL-6 protein expression was identified in affected tissues by immunohistochemical localization. In contrast, no evidence of KSHV coinfection was detected in any of 31 EBV-related posttransplant lymphoproliferative disorders or 112 non-PEL lymphomas tested. The pathologic findings in these two patients were not representative of malignancy by morphologic, immunophenotypic, or molecular criteria. This study underscores the marked propensity for hematolymphoid proliferations associated with KSHV infections to show plasmacytic features. Additionally, this study describes use of an antibody reactive against KSHV vIL-6 that can readily detect a subpopulation of KSHV-infected hematopoietic cells.

J Infect. 2000 May;40(3):242-7.

Human herpesvirus type 8 in HIV-infected patients with interstitial pneumonitis.

Muller A, Franzen C, Klussmann P, Wagner M, Diehl V, Fatkenheuer G, Salzberger B, Ablashi DV, Krueger GR.

Department of Pediatrics, University of Cologne, Germany.

OBJECTIVES: The new human herpesvirus type 8 (HHV-8) has been detected in all types of Kaposi's sarcomas, as well as in body-cavity lymphomas and Castleman's disease. Recently, HHV-8 has also been associated with encephalitis in HIV-positive and HIV-negative patients. Interstitial pneumonitis, combined with detection of HHV-8 in non HIV-infected patients, indicates a pathogenetic role of HHV-8 in unexplained lung diseases. We have studied two HIV-infected patients, with otherwise unexplained interstitial pneumonitis for the presence of HHV-8. METHODS: Lung biopsies of both patients were investigated for HHV-8 sequences. A nested PCR method was used for amplification of HHV-8 DNA fragments, and the nature of the amplification products was confirmed by Southern blot hybridization. In addition, we used an in situ hybridization technique and immunohistochemical staining for detection of HHV-8 infected cells. RESULTS: Amplification of HHV-8 DNA fragments was seen with template DNA from lung biopsies of both cases and the appropriate positive controls, but not with negative controls. In situ hybridization and immunohistochemical staining demonstrated HHV-8 infected lymphoid cells and alveolar macrophages in both patients as well. CONCLUSIONS: HHV-8 was found in HIV-infected patients with otherwise unexplained interstitial pneumonitis, but the pathogenic role of HHV-8 in patients with interstitial pneumonia remains unclear.

ATTENZIONE!

HHV-8 PUO' ESSERE ESPRESSO ANCHE IN LESIONI VASCOLARI NON KAPOSI

Am J Surg Pathol. 2002 Jun;26(6):685-97.

Reactive angioendotheliomatosis: a study of 15 cases demonstrating a wide clinicopathologic spectrum.

McMenamin ME, Fletcher CD.

Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

Reactive angioendotheliomatosis (RAE) is a rare condition characterized by cutaneous vascular proliferation that usually occurs in patients with diverse types of coexistent systemic disease. Although intravascular proliferation of endothelial cells has been considered to be the key histologic feature in RAE, other patterns of vascular proliferation have also been described. We reviewed the clinicopathologic features in 15 cases of RAE. The study group comprised eight males and seven females with an age range of 47-88 years (median 65 years). Eleven patients had coexistent systemic disease: renal disease (six patients, including three post renal transplantation); valvular cardiac disease (two patients); one patient each had alcoholic cirrhosis, glioblastoma multiforme (on chemotherapy), and rheumatoid arthritis/polymyalgia rheumatica. Six patients were iatrogenically immunosuppressed at the onset of the skin lesions. The clinical appearance included multiple erythematous macules, plaques, tumors, and ulcerated lesions, with a wide distribution but a propensity to involve limbs. Lesions had been present for 1 month to 4 years (median 4 months). Lesions resolved in four cases, improved in two cases, remained static in one case, and progressed in four cases. Two cases were recent and follow-up was not available in two other cases. Three patients died of their coexistent systemic disease with resolution, improvement, and progression of lesions, respectively. All lesions were characterized histologically by a proliferation of capillaries in the dermis, with variably diffuse (seven cases), lobular (six cases), or mixed lobular and diffuse patterns (two cases). There was marked intercase and intracase heterogeneity in histologic features. Common features included fibrin microthrombi (nine cases), reactive (fasciitis-like) dermal alterations (seven cases), and foci of epithelioid endothelium (four cases). Four of 10 cases tested showed positive immunohistochemical staining for HHV-8 latent nuclear antigen in lesional endothelial cell nuclei. This study suggests that RAE has a broader clinicopathologic spectrum than previously described. The pathogenesis of this rare disorder is unknown, but it is likely that immunologic factors play a role.

Luglio 2003

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