Detection of infectious simian immunodeficiency virus in B- and T-cell lymphomas of experimentally infected macaques.
An increasing frequency of malignant lymphomas occurs among patients infected by human immunodeficiency virus. Because of the close similarities to human malignancies, we used a nonhuman primate model to study the pathogenesis of simian immunodeficiency virus (SIV)-associated malignancies. Specifically, we investigated (1) the presence of the SIV genome in tumor cells, (2) the presence of coinfecting viruses, and (3) the presence of a rearrangement of the immunoglobulin and c-myc genes. We observed 5 cases of non-Hodgkin's lymphomas (4 of B- and 1 of T-cell origin) among 14 SIV-infected cynomolgus monkeys. No c-myc translocation was observed in the tumors, whereas B-cell lymphomas were characterized either by a monoclonal (in 2 of 4) or by an oligoclonal (in 2 of 4) VDJ rearrangements of the immunoglobulin heavy chain gene. Molecular, biological, and immunological analyses did show the presence of infectious SIV in the tumor cells of 1 T-cell and 2 oligoclonal B-cell lymphomas. Neither Simian T-lymphotropic nor Epstein-Barr viruses were detectable, whereas Simian herpes virus Macaca fascicularis-1 was detectable at a very low copy number in 3 of 4 B-cell lymphomas; however, only 1 of these also harbored the SIV genome. These results support the possibility that SIV may be directly involved in the process of B or T lymphomagenesis occurring in simian acquired immunodeficiency syndrome.
Maggiorella
M T
MT
Laboratory of Virology, Istituto Superiore Sanità, Rome, Italy.
Monardo
F
F
Koanga-Mogtomo
M L
ML
Cioè
L
L
Sernicola
L
L
Corrias
F
F
Baroni
C D
CD
Verani
P
P
Titti
F
F
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D002999:Clone Cells; D004279:DNA, Viral / Q000235:genetics; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D016259:Genes, myc; D016393:Lymphoma, B-Cell / Q000473:pathology / Q000821:virology*; D016399:Lymphoma, T-Cell / Q000473:pathology / Q000821:virology*; D008252:Macaca fascicularis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000254:growth & development*; D015303:Simian T-lymphotropic virus 1 / Q000235:genetics; D014178:Translocation, Genetic
D000914:Antibodies, Viral; D004279:DNA, Viral