Primary characterization of a herpesvirus agent associated with Kaposi's sarcomae

Abstract

Detection of novel DNA sequences in Kaposi's sarcoma (KS) and AIDS-related body cavity-based, non-Hodgkin's lymphomas suggests that these neoplasms are caused by a previously unidentified human herpesvirus. We have characterized this agent using a continuously infected B-lymphocyte cell line derived from an AIDS-related lymphoma and a genomic library made from a KS lesion. In this cell line, the agent has a large episomal genome with an electrophoretic mobility similar to that of 270-kb linear DNA markers during clamped homogeneous electric field gel electrophoresis. A 20.7-kb region of the genome has been completely sequenced, and within this region, 17 partial and complete open reading frames are present; all except one have sequence and positional homology to known gammaherpesvirus genes, including the major capsid protein and thymidine kinase genes. Phylogenetic analyses using both single genes and combined gene sets demonstrated that the agent is a gamma-2 herpesvirus (genus Rhadinovirus) and is the first member of this genus known to infect humans. Evidence for transient viral transmission from infected to uninfected cells is presented, but replication-competent virions have not been identified in infected cell lines. Sera from patients with KS have specific antibodies directed against antigens of infected cell lines, and these antibodies are generally absent in sera from patients with AIDS without KS. These studies define the agent as a new human herpesvirus provisionally assigned the descriptive name KS-associated herpesvirus; its formal designation is likely to be human herpesvirus 8.

Identification of gammaherpesvirus infection in free-ranging black bears (Ursus americanus)

“…associated herpesvirus (KSHV), and Murine gammaherpesvirus-68 (MHV-68) are most studied rhadinoviruses. HHV8 or KHSV is mainly linked to the development of Kaposi's sarcoma and a rare B cell lymphoma, primary effusion lymphoma in human (Moore et al, 1996;Wong and Damania, 2005). However, both HHV-4 and HHV8 are…”

Complex Alternative Cytoplasmic Protein Isoforms of the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Generated through Noncanonical Translation Initiation

“…In addition to its role in latent viral genome replication and segregation, it targets multiple cellular tumor suppressor genes, such as p53 and retinoblastoma (Rb) (4)(5)(6), and ribosomal subunit, chromatin remodeling, and transcriptional factor proteins (7)(8)(9). LANA1 was first discovered as a nuclear protein through adsorption studies using KSHV-negative cells and Kaposi's sarcoma patient sera (10). Patient antibodies to LANA1 were found to be specific for KSHV infection, and this was confirmed and extended in studies performed by Gao et al (11) and Kedes et al (12) to define the natural history of KSHV infection and KS.…”

Kaposi's sarcoma‐associated herpesvirus DNA sequences in AIDS‐related and AIDS‐unrelated lymphomatous effusions

“…agent has been subsequently characterized using a continuously infected B-lymphocyte cell line derived from an AIDSrelated BCBL (Moore et al, 1996). Although the virus has been given the descriptive name 'Kaposi's sarcoma-associated herpesvirus (KSHV)' (Chang et al, 1994), the term 'human herpesvirus-8 (HHV-8)' has been proposed as its formal designation (Moore et al, 1996).…”