Gammaherpesviruses are lymphotropic viruses known to induce tumors, particularly in the setting of immunocompromise such as AIDS. Gammaherpesviruses are species-specific, thus limiting our ability to study them in vivo. Murine Gammaherpesvirus-68 (MHV68) mimics key aspects of both EBV and KSHV infection, including the establishment of latency in B cells and the formation of B cell lymphomas. This model allows us to dissect key molecular events involved in in vivo infection and disease. Lytic replication, which occurs during an acute infection, masks the events that prepare the viral genome for latency. Epigenetic modifications of the viral genome have been shown to be essential for regulating gene expression and driving the virus into latency. To identify the key epigenetic events that facilitate long-term MHV68 latency, I will use two similar replication-defective mutant viruses, one that establishes normal B-cell latency, and one that is attenuated for B-cell latency. Using ChIP-Seq analysis, I will determine the location of epigenetic modifications present on these two viral genomes at multiple stages of in vivo infection, including the earliest moments following viral entry. These data will be used to specifically identify epigenetic marks that facilitate the establishment of life-long gammaherpesvirus latency in B cells.

Public Health Relevance

Human gammaherpesviruses such as EBV and KSHV are associated with the development of multiple types of tumors, particularly during immune suppression such as that which occurs with AIDS. The work proposed here will define the specific epigenetic modifications to the virus genome that are required for the establishment of life-long infection. Understanding these key modifications will facilitate the development of therapeutics to combat the onset of disease.

Agency
National Institute of Health (NIH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI106559-01A1
Application #
8732044
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Beisel, Christopher E
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Florida
Department
Genetics
Type
Schools of Medicine
DUNS #
City
Gainesville
State
FL
Country
United States
Zip Code
32611