Kaposi?s sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi?s sarcoma (KS): especially, oral KS is one of the most common HIV-associated neoplasms. A number of studies have indicated that lymphangiogenic pathways are directly involved in KSHV malignancy. Thus, the proposed study is directed toward investigating how KSHV regulates the lymphangiogenic pathway, which may ultimately be used to design a targeted therapeutic strategy to block KSHV-induced malignancy. Based on our findings, we hypothesize that the KSHV vIRF3 latent protein directs HDAC5 angiogenic factor to induce the global gene expression change and hyper-sprouting formation for virus-induced lymphangiogenesis, which is a potential target for therapeutic strategy. In this proposal, we will study how the vIRF3 interaction blocks the phosphorylation-induced nuclear export of HDAC5; why vIRF3 functions are apparent only in LECs but not in BECs; and whether loss of the vIRF3 function affects KSHV oncogenesis in cultures. This proposal is targeted to enhance our understanding how KSHV deregulates lymphangiogenic pathway and thus should inform therapeutic strategies to block KSHV-induced malignancy, specifically oral KS.

Public Health Relevance

Kaposi?s sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi?s sarcoma (KS): especially, oral KS is one of the most common HIV-associated neoplasms. A number of studies have indicated that lymphangiogenic pathways are directly involved in KSHV malignancy. Thus, the proposed study is directed toward investigating how KSHV regulates the lymphangiogenic pathway, which may ultimately be used to design a targeted therapeutic strategy to block KSHV-induced malignancy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DE027888-01
Application #
9548515
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lunsford, Dwayne
Project Start
2018-09-05
Project End
2020-08-31
Budget Start
2018-09-05
Budget End
2019-08-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Southern California
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089