Examining the effect of producer cell-type on the target cell tropism of KSHV

Authors

• TD Maldonado
• EA Brenner
• SJ Dollery
• EA Berger

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is a member of the gammaherpesvirus-8 family. KSHV is the causative agent of Kaposi's sarcoma, a cancer of endothelial origin, and two B-cell lymphoproliferative disorders: primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). During infection, the default mode of replication is the latent cycle and B-cells are believed to be the reservoir cell type. While in vivo, KSHV has a broad tropism spectrum, in vitro studies are hampered by the absence of a B cell model of infection and low levels of virus production. We question whether producer cell type might influence tropism of KSHV progeny, as is known for Epstein-Barr virus and other gammaherpesviruses. In order to answer this, enhanced producer cells were engineered. Several types were generated that contain the recombinant (r)KSHV.219 virus and the replication and transcription activator (RTA) under the control of a doxycycline-inducible Tet-On trans-activator system. Inducible cells (i) iMC116 (human B cell), iTIME (epithelial), iSLK (human epithelial) and iVero (primate epithelial), were exposed to a range of concentrations of Sodium Butyrate and Doxycycline, levels of virus production were examined. KSHV was harvested from cell types and exposed to a range of target cell types. KSHV produced by iVero and iSLK cells preferentially infected Vero and SLK while virus produced from iMC116 had a greatly diminished relative ability to infect Vero cells but not MC116. These results suggest that KSHV relative tropism can alter upon producer cell type. This has implications for both pathogenesis and transmission of the virus.

Scientific Focus Area: Virology

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