Experimental rhesus lymphocryptovirus infection in immunosuppressed macaques: an animal model for Epstein-Barr virus pathogenesis in the immunosuppressed host.
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.
Rivailler
Pierre
P
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Carville
Angela
A
Kaur
Amitinder
A
Rao
Pasupuleti
P
Quink
Carol
C
Kutok
Jeffery L
JL
Westmoreland
Susan
S
Klumpp
Sherry
S
Simon
Meredith
M
Aster
Jon C
JC
Wang
Fred
F
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
D000914:Antibodies, Viral