The human genome is not a linear sequence, but rather a contorted knot of chromosomes in the three- dimensional space of the nucleus. Chromosomes do not work in isolation. Long-range interactions regulate gene expression. This innovation, however, has not been applied to viral infections. We still talk of host and pathogen genomes as if they are independent. I contend that these genomes are not separate, but rather an intertwined entity best referred to as a "hosthogen" genome. I propose to study long-range interactions between the human genome and latent Epstein-Barr virus (EBV). We will focus on connections mediated by the CCCTC-binding factor, a protein known to assemble interchromosomal loops. We have developed a method, the associated chromatin trap assay followed by deep sequencing (ACT-seq), to detect intergenome loops in a cell culture model of lymphoma. Persistent infection with EBV drives the development of cancer in AIDS survivors. This work may thus identify new drug targets that control viral genes responsible for HIV-associated malignancies.

Public Health Relevance

Persistent infection with Epstein-Barr virus drives the development of cancer in AIDS survivors. We seek to understand how this viral genome is tied up with the human genome in three-dimensional space. Our work may thus identify new drug targets that control viral genes responsible for HIV-associated malignancies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI108597-01A1
Application #
8659940
Study Section
AIDS-associated Opportunistic Infections and Cancer Study Section (AOIC)
Program Officer
Beisel, Christopher E
Project Start
2014-08-01
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$286,500
Indirect Cost
$136,500
Name
J. David Gladstone Institutes
Department
Type
DUNS #
099992430
City
San Francisco
State
CA
Country
United States
Zip Code
94158