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

TLDR

Novel DNA sequences detected in Kaposi's sarcoma and AIDS‑related lymphomas indicate a previously unidentified human herpesvirus as the likely cause. The virus was characterized by culturing a continuously infected B‑lymphocyte line from an AIDS‑related lymphoma and constructing a genomic library from a KS lesion. Sequencing and phylogenetic analysis revealed a large episomal genome with 17 gamma‑herpesvirus‑like ORFs, placing the virus in the Rhadinovirus genus as the first human member, and serological evidence showed KS patients possess specific antibodies, supporting its role as a novel human herpesvirus, provisionally named KS‑associated herpesvirus (human herpesvirus 8).

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.