Morphogenesis of HHV8 in primary human dermal microvascular endothelium and primary effusion lymphomas.

This study elucidates the morphology of HHV8 replication in human dermal endothelial cells and primary effusion lymphomas (PEL) and compares it to that seen in Kaposi sarcoma. Primary human dermal microvascular endothelial cells (DMVEC) exposed to the cell-filtered supernatant of the PEL JSC1 and PEL cell lines (KS-1, BCBL-1, BC-1, BC-3) were cultured in the presence or absence of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or butyrate. Cells were fixed in neutral-buffered glutaraldehyde, gelled in cooled agar, and processed for TEM. There was a quantitative, but not a qualitative difference in viral expression associated with no treatment or exposure to TPA or butyrate of H HV8 in DMVEC and PEL. Two types of viral-induced intranuclear inclusions (INI) were visible at the light and ultrastructural levels. The more common INI had lighter staining material filling the nucleus, except for a rim of dense chromatin, and could be seen even before viral nucleocapsids (NC) were visible. The second type of INI resembled a target formed by condensation of electron-dense material surrounded by a lighter halo and marginated heterochromatin and containing NC. Collections of coalescing electron-dense granules resembling starbursts were often present in nuclei containing either type of INI. Next to appear in productively infected cells were mature enveloped particles that formed mostly by the budding of NC into cytoplasmic vacuoles. Mature particles were also seen free on the plasma membrane. Tufts of electron-dense intermediate filaments were associated with maturing particles. Mature virions lacked an electron-dense tegument. Viral production was ultimately associated with cell lysis. It appears that HHV8 propagate in DMVEC, with and without stimulation, and have a similar morphogenesis to that seen in PEL cell lines and Kaposi sarcoma lesions. Several unique features characterize cells productively infected by HHV8.

Lytic growth of human herpesvirus 8: morphological aspects.

The human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, is a gamma herpesvirus associated with AIDS-related body cavity-based lymphomas (BCBL), also called primary effusion lymphomas (PEL). These are a rare form of non-Hodgkin lymphomas in which HHV-8 is present, often associated with Epstein-Barr virus (EBV) infection. HHV-8 is also present in a latent state or in a state of low-level persistence in different primary effusion lymphoma-derived cell lines, such BCBL-1 cells, that lack EBV infection. This cell line was induced to produce mature virions by treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA) and the characteristic ultrastructural features of HHV-8 lytic replication were identified and compared to those of the other members of Herpesviridae family.

True histiocytic lymphoma of the esophagus in an HIV-positive patient: an ultrastructural study.

A 56-year-old white woman, seropositive for human immunodeficiency virus for 18 months without signs of acquired immunodeficiency syndrome, presented with retrosternal pain and progressive dysphagia secondary to an exophytic esophageal mass. Biopsies of the tumor showed a malignant neoplasm composed of pleomorphic, noncohesive cells growing in a diffuse, sheet-like fashion. Immunohistochemically, tumor cells were nonreactive with epithelial, lymphoid, neural, and monocyte/macrophage markers. Despite the noncontributory immunohistochemical findings, ultrastructural study of the tumor cells revealed convincing histiocytic features. Individual cells possessed long, slender filopodial projections, prominent Golgi apparatus, residual bodies, rare lysosomes, and prelysosomes. Immunoglobulin heavy chain and T-cell receptor gamma gene rearrangement studies detected no evidence of a clonal gene rearrangement. The patient responded poorly to chemotherapy and died 5 months after her initial symptom of dysphagia.

Molecular and pathologic characterization of an AIDS-related body cavity-based lymphoma, including ultrastructural demonstration of human herpesvirus-8: a case report.

Body cavity-based lymphoma, also known as primary effusion lymphoma, is a newly recognized acquired immunodeficiency syndrome (AIDS)-related lymphoma that has been linked to the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). To date, direct visualization of the virus in a clinical sample has not been demonstrated. We have performed an extensive clinical, histologic, immunophenotypic, ultrastructural, and molecular genetic correlative study on multiple tissue samples obtained premortem and at autopsy from an patient with AIDS with Kaposi's sarcoma and body cavity-based lymphomas. We demonstrate the presence of human herpesvirus-8 in a primary clinical sample at the ultrastructural and molecular level, as well as document multiple lymphomatous tumor masses at autopsy.