Human Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are the leading etiological agents that cause morbidity and mortality in immune compromised patients. Currently, we do not have good animal models to study these oncogenic human pathogens. Closely related to human KSHV and EBV, murine gamma herpesvirus 68 infects laboratory mice, undergoes robust lytic replication in the lung and establishes persistent infection in the spleen. This provides an excellent small animal model to study gamma herpesvirus infection in vivo. However, murine gamma herpesvirus 68 infection causes limited pathogenesis in laboratory mouse strains, offering minimal insights into diseases, e.g., cancers associated with KSHV and EBV. The goal of this study is to develop a surrogate system that enables the interrogation of host-virus interactions in virally-induced tumorigenesis, in the context of viral infection. Accordingly, the specific aims of this proposal are to: 1) engineer recombinant murine gamma herpesvirus 68 that carries the prominent KSHV oncogene, kGPCR, and examine viral replication in culture and infection in mice, and 2) to evaluate the tumorigenicity of recombinant gamma herpesvirus 68 in normal and immune- compromised mice, focusing on lymphoproliferative and Kaposi's sarcoma-like diseases. This study will provide a valuable platform to dissect viral oncogenesis that is truly induced during viral infection.

Public Health Relevance

Human Kaposi's sarcoma-associated herpesvirus is the leading etiological agent that causes morbidity and mortality in immune compromised patients and currently, we do not have good animal models to study this oncogenic human pathogen. The goal of this study is to develop a surrogate system that enables the interrogation of host-virus interactions in virally-induced tumorigenesis, in the context of viral infection. This study will provide a valuable platform to dissect viral oncogenesi that is truly induced during viral infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI105340-01A1
Application #
8638543
Study Section
Virology - B Study Section (VIRB)
Program Officer
Beisel, Christopher E
Project Start
2013-12-15
Project End
2015-11-30
Budget Start
2013-12-15
Budget End
2014-11-30
Support Year
1
Fiscal Year
2014
Total Cost
$221,681
Indirect Cost
$86,681
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