Kaposi sarcoma associated herpesvirus (KSHV) reprograms cells upon infection. One other outcome of this reprogramming is cellular transformation, such that KSHV-infected cells give rise to human cancer. KSHV causes cancers of two different cell lineages: B cells and endothelial cells. KSHV reprograms endothelial cells to adopt a lymphatic phenotype and induces hyperplasia of these lymphatic endothelial cells. This eventually leads to the emergence of Kaposi sarcoma (KS). KSHV reprograms B cells, though it is unclear exactly which subset and what the direct outcome is. Eventually this, too, leads to complete transformation and the emergence of signature, KSHV-associated, B cell cancers, i.e. a subclass of multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL). We hypothesize that this reprogramming is mediated, at least in part, by viral and cellular micro RNAs. We previously identified KS specific cellular miRNAs and we will investigate their regulation in KS biopsies and culture models. We generated in KSHV miRNA transgenic mice and will investigate their phenotypes with regard to B cell function and oncogene cooperation.

Public Health Relevance

This is application to continue our work on understanding the principal latent genes of Kaposi sarcoma associated herpesvirus (KSHV). KSHV causes cancers in the context of HIV/AIDS and the viral latent genes in particular the viral mirRNAs exhibit oncogenic properties. Understanding their function and regulation will help unravel the biology of cancers causes by KSHV and, we hope, provide novel targets for intervention.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA019014-33
Application #
8380195
Study Section
Special Emphasis Panel (ZCA1-RPRB-0)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
33
Fiscal Year
2012
Total Cost
$291,273
Indirect Cost
$83,994
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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