The complex kaposin locus of Kaposi's sarcoma-associated herpesvirus: defining a new role in the lytic viral replication cycle

Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of the endothelial cell (EC) cancer, Kaposi’s sarcoma, and two B-cell malignancies. In infected cells, the virus exists in two states; the latent program alters cell morphology and inflammatory gene expression, while the lytic cycle produces new virus and promotes tumorigenesis in a paracrine manner. The kaposin locus, located in the latent gene cluster, generates multiple transcripts and gene products in both viral states; however, its function remains unclear. I developed a library of novel recombinant viruses to mutagenize kaposin coding capacity and investigate protein-specific effects during each viral life cycle. I found that while entry and latent gene expression were unaffected by kaposin mutagenesis, the ability to reprogram ECs may be impaired. Furthermore, I identified defects in lytic viral gene expression and virion production in some kaposin-mutant viruses, leading me to suggest new roles for the kaposins in lytic cycle progression.