Epstein Barr virus is the cause of infectious mononucleosis and is associated with a number of cancers including Hodgkin's disease and Burkitt's lymphoma. Chronic active Epstein-Barr virus is a rare disease in which persons have persistent organ disease due to the virus that lasts for more than six months. We are studying patients with chronic active Epstein-Barr virus to try to determine the cause of this disease. Patients with the X-linked lymphoproliferative disorder (XLPD) develop fulminant mononucleosis and those who survive have a clinical course that has some features in common with CAEBV. Patients with XLPD have mutations in the SAP protein. Since some patients with CAEBV have been reported to have defects in killing of target cells by their white blood cells, we have focused on proteins, such as interferon alpha and gamma, which are important for white blood cells to kill virus-infected cells. Sequencing of the SAP gene and the interferon gamma receptor gene have not shown any mutations in patients with CAEBV. Current studies are focusing on other proteins that mediate killing of virus-infected cells such as perforin and granzymes. Preliminary experiments have identified novel mutations in both copies of the perforin gene in a patient who died with CAEBV. The patient had a very low level of perforin in his white blood cells compared with healthy blood donors, and he had an abnormal accumulation of a precursor form of perforin.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Niaid Extramural Activities
United States
Zip Code
Cohen, Jeffrey I; Fauci, Anthony S; Varmus, Harold et al. (2011) Epstein-Barr virus: an important vaccine target for cancer prevention. Sci Transl Med 3:107fs7
Sashihara, Junji; Burbelo, Peter D; Savoldo, Barbara et al. (2009) Human antibody titers to Epstein-Barr Virus (EBV) gp350 correlate with neutralization of infectivity better than antibody titers to EBV gp42 using a rapid flow cytometry-based EBV neutralization assay. Virology 391:249-56
Hoover, Susan E; Kawada, Junichi; Wilson, Wyndham et al. (2008) Oropharyngeal shedding of Epstein-Barr virus in the absence of circulating B cells. J Infect Dis 198:318-23
Lunemann, Jan D; Frey, Oliver; Eidner, Thorsten et al. (2008) Increased frequency of EBV-specific effector memory CD8+ T cells correlates with higher viral load in rheumatoid arthritis. J Immunol 181:991-1000
Tosato, Giovanna; Cohen, Jeffrey I (2007) Generation of Epstein-Barr Virus (EBV)-immortalized B cell lines. Curr Protoc Immunol Chapter 7:Unit 7.22
Scheinberg, Phillip; Fischer, Steven H; Li, Li et al. (2007) Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia. Blood 109:3219-24
Zou, Ping; Kawada, Junichi; Pesnicak, Lesley et al. (2007) Bortezomib induces apoptosis of Epstein-Barr virus (EBV)-transformed B cells and prolongs survival of mice inoculated with EBV-transformed B cells. J Virol 81:10029-36
Cohen, J I (2005) HMG CoA reductase inhibitors (statins) to treat Epstein-Barr virus-driven lymphoma. Br J Cancer 92:1593-8
Katano, Harutaka; Cohen, Jeffrey I (2005) Perforin and lymphohistiocytic proliferative disorders. Br J Haematol 128:739-50
Katano, Harutaka; Ali, Mir A; Patera, Andriani C et al. (2004) Chronic active Epstein-Barr virus infection associated with mutations in perforin that impair its maturation. Blood 103:1244-52

Showing the most recent 10 out of 13 publications