A unique herpesviral transcriptional program in KSHV-infected lymphatic endothelial cells leads to mTORC1 activation and rapamycin sensitivity.

ABSTRACT: Immunosuppression therapy following organ transplantation is a significant factor in the development and progression of Kaposi's sarcoma-associated herpesvirus (KSHV)-induced posttransplant Kaposi's sarcoma (KS). Switching from cyclosporine to the mTOR inhibitor rapamycin is reported to promote KS regression without allograft rejection. Examining the underlying molecular basis for this clinical observation, we find that KSHV infection selectively upregulates mTOR signaling in primary human lymphatic endothelial cells (LECs), but not blood endothelial cells (BECs), and sensitizes LECs to rapamycin-induced apoptosis. Viral transcriptome analysis revealed that while infected BECs display conventional latency, KSHV-infected LECs support a radically different program involving widespread deregu

SUBMITTER: Chang HH 

PROVIDER: S-EPMC3774835 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature