A monkey model for Epstein Barr virus-associated lymphomagenesis in human acquired immunodeficiency syndrome.
High-grade malignant nonHodgkin's lymphomas--five lymphoblastic, three pleomorphic, and two immunoblastic--developed in 10/25 cynomolgus monkeys (Macaca fascicularis) followed for up to 746 d after infection with simian immunodeficiency virus, strain SIVsm. These lymphomas were shown to be associated with an Epstein-Barr (EB)-like cynomolgus B-lymphotropic herpesvirus (CBLV) by electron microscopy, by Southern blot hybridization with probes against human EBV, and by the expression of antigens corresponding to EBV-associated nuclear antigens (EBNAs) involved in human B cells transformation. Southern blot demonstration of immunoglobulin gene rearrangements and homogeneous EBV episomes indicated that all the lymphomas were CBLV-associated monoclonal B cell proliferations. Our findings suggest that these tumors correspond to the EBV-associated malignant lymphomas in acquired immunodeficiency syndrome with respect to clinical, morphological, phenotypic, and genotypic characteristics. The particular susceptibility of SIVsm immunodeficient cynomolgus monkeys for CBLV-associated lymphomagenesis appears therefore a useful model for EBV-associated lymphomas in humans.
Feichtinger
H
H
Department of Pathology, University of Innsbruck, Austria.
Li
S L
SL
Kaaya
E
E
Putkonen
P
P
Grünewald
K
K
Weyrer
K
K
Böttiger
D
D
Ernberg
I
I
Linde
A
A
Biberfeld
G
G
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D015139:Blotting, Southern; D004195:Disease Models, Animal; D019309:Epstein-Barr Virus Nuclear Antigens; D005803:Genes, Immunoglobulin; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity*; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology*; D008252:Macaca fascicularis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications*
D000956:Antigens, Viral; D019309:Epstein-Barr Virus Nuclear Antigens