Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Host Microbe. 2013 Apr 17;13(4):429-40. doi: 10.1016/j.chom.2013.03.009.

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

Author information

1
Novartis Institutes for BioMedical Research, Emeryville, CA 94608, USA.

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 deregulation of both latent and lytic genes. ORF45, a lytic gene selectively expressed in infected LECs, is required for mTOR activation and critical for rapamycin sensitivity. These studies reveal the existence of a unique herpesviral gene expression program corresponding to neither canonical latency nor lytic replication, with important pathogenetic and therapeutic consequences.

Comment in

PMID:
23601105
PMCID:
PMC3774835
DOI:
10.1016/j.chom.2013.03.009
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center