Kaposi's sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells

Abstract

The recent discovery of DNA sequences of a new human herpesvirus in Kaposi's sarcoma (KS) has fueled speculation that this virus might cause KS. The mere presence, however, of a virus in a complex multicellular tumor like KS could just as well be construed as evidence of a passenger agent. We sought stronger evidence linking the KS-associated herpesvirus (KSHV) to tumor formation by using in situ hybridization to investigate the specificity, constancy, and timing of KSHV gene expression in KS tumor cells. Here we document expression of a 700-nucleotide viral RNA in every KS tumor examined, from the earliest histologically recognizable stage to advanced tumors in which the vast majority of identifiable spindle tumor cells contain this transcript. Two other KSHV RNAs were also detected in a smaller fraction of the tumor cells in all but the earliest lesion. These viral RNAs were expressed to relatively low levels in this subset; because one of these RNAs encodes a major viral capsid protein, these cells may be producing KSHV. We did not find these KSHV genes expressed in a variety of other tumors and proliferative processes, but we did detect viral gene expression in prostatic tissue, supporting a possible mechanism for sexual transmission of KSHV. The close relationship between KS and KSHV gene expression is consistent with the hypothesis that KSHV is directly involved in the etiology and pathogenesis of KS.

Induction of lytic cycle replication of Kaposi's sarcoma-associated herpesvirus by herpes simplex virus type 1: involvement of IL-10 and IL-4

“…In KS lesions, latent KSHV predominates with a low percentage of cells exhibiting lytic replication; the viral genome persists as an episome and has highly restricted expression of latent genes. The latent phase is essential for the development of KSHV-induced malignancies (Staskus et al, 1997). The lytic phase, during which the virus produces infectious virions for dissemination, modulates cellular signalling pathways through unrestricted expression of viral genes (Dourmishev et al, 2003).…”

Species-independent detection of RNA virus by representational difference analysis using non-ribosomal hexanucleotides for reverse transcription

“…For commercial re-use, please contact journals.permissions@oupjournals.org from a Kaposi's sarcoma (KS) lesion in an AIDS patient. The determination of sequences of these fragments resulted in the discovery of the KS-associated herpes virus (7). Despite the fact that RDA has been developed for detecting agents with a DNA-based genome, it can be used to detect the presence or absence of RNA in a sample by generating a cDNA intermediate (cDNA RDA) to amplify the RNA (8).…”

A Functional Genomics Approach to Kaposi's Sarcoma

“…8 In the KS lesion, KSHV infects the majority of spindle cells as well as lesional endothelial cells and infiltrating leukocytes. [9][10][11][12] KSHV genes with the potential to deregulate cellular growth have been described, many of which are homologous to cellular genes. 13 Despite the recognition that KSHV encodes a variety of proteins that could conceivably induce and/or maintain KS lesions, the mechanisms of virus-induced oncogenesis remain unclear.…”