Abortive Lytic Reactivation of Kapose's Sarcoma Associated Virus (KSHV) in CBF1/CSL Deficient Human B Cells

CBF1/CSL is a cellular DNA binding protein that can recruit transactivators or repressors to regulatory sites in the viral and cellular genome. We have used a novel cell culture model to analyze the impact of CBF1/CSL signalling on the process of viral reactivation of Kaposi's sarcoma associated herpesvirus (KSHV) in human B cells. Two isogenic CBF1/CSL proficient or deficient B cell lines were latently infected with recombinant KSHV. Lytic viral gene expression, viral replication and virus production were compared. Our results suggest that viral lytic gene expression is severely attenuated but not abolished at multiple stages before and after the onset of lytic replication while virus production is below detection levels in CBF1/CSL deficient B cells. Thus, CBF1/CSL acts as a cellular hub which is used by the virus to coordinate the lytic cascade in KSHV infected B cells to produce viral progeny.>

Background:

Kaposi's sarcoma associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS) which is a proliferative disorder of endothelial origin. KSHV is a g-herpesvirus which establishes a life-long persistent infection in the B cell compartment of the infected human host. Lytic cycle activation of KSHV is considered to be an essential step in the pathogenesis of KS which is still a major health problem of HIV infected persons which do not have access to effective anti-HIV treatment and a serious problem in the aging population of geographic areas characterized by elevated KSHV prevalence.

Publication:
Scholz, B.A., Harth-Hertle, M.L., Malterer, G., Haas, J., Ellwart, J., Schulz, T.F., and Kempkes, B. (2013). Abortive lytic reactivation of KSHV in CBF1/CSL deficient human B cell lines. PLoS Pathog 9, e1003336

Person to contact for further enquiries:
Bettina Kempkes, kempkesnoSp@m@helmholtz-muenchen.de, 089-3187-1354>