title: Experimental rhesus lymphocryptovirus infection in immunosuppressed macaques: an animal model for Epstein-Barr virus pathogenesis in the immunosuppressed host.
abstract: To develop a model for Epstein-Barr virus (EBV) pathogenesis in immunosuppressed hosts, we studied experimental infections of immunocompetent versus SHIV 89.6P-infected, immunosuppressed rhesus macaques with the EBV-related rhesus lymphocryptovirus (LCV). Primary LCV infection after oral inoculation of 4 immunocompetent animals was characterized by an acute viremia and seroconversion followed by asymptomatic LCV persistence. Four immunosuppressed macaques infected orally with LCV failed to develop an LCV-specific humoral response and viremia was more pronounced, but there was no evidence of LCV-induced lymphoproliferative disease. A more aggressive primary challenge was administered by intravenous inoculation of 10(8) autologous, LCV-immortalized B cells in 4 additional immunosuppressed animals. Two animals with modest immunosuppression remained asymptomatic, and 1 of 2 severely immunosuppressed animals developed an aggressive, monoclonal LCV-positive lymphoma. These studies demonstrate the potential for lymphomagenesis in an experimental model system for EBV infection and underscore the strength and depth of immune control in limiting LCV-induced lymphoproliferative disease.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Rivailler
authors.forename: Angela
authors.initials: A
authors.lastname: Carville
authors.forename: Amitinder
authors.initials: A
authors.lastname: Kaur
authors.forename: Pasupuleti
authors.initials: P
authors.lastname: Rao
authors.forename: Carol
authors.initials: C
authors.lastname: Quink
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Kutok
authors.forename: Susan
authors.initials: S
authors.lastname: Westmoreland
authors.forename: Sherry
authors.initials: S
authors.lastname: Klumpp
authors.forename: Meredith
authors.initials: M
authors.lastname: Simon
authors.forename: Jon C
authors.initials: JC
authors.lastname: Aster
authors.forename: Fred
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D018791:CD4 Lymphocyte Count; D002461:Cell Line, Transformed; D004195:Disease Models, Animal; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology*; D006566:Herpesviridae Infections / Q000150:complications / Q000276:immunology*; D007121:Immunocompetence; D016867:Immunocompromised Host; D018143:Lymphocryptovirus; D008223:Lymphoma / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000276:immunology
chemical_list: D000914:Antibodies, Viral