Detection of Infectious Simian Immunodeficiency Virus in B- and T-Cell Lymphomas of Experimentally Infected Macaques

Abstract

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.

Macaque Homologs of EBV and KSHV Show Uniquely Different Associations with Simian AIDS-related Lymphomas

“…We analyzed a panel of macaque lymphomas collected at the WaNPRC over the past 30 years with the goal of elucidating the role of macaque gammaherpesviruses in simian AIDS-related lymphomagenesis. In previous published studies, macaque LCV homologs of EBV were detected in the vast majority of lymphomas by non-quantitative PCR techniques, with detection rates ranging from 75–100% [24] , [25] , [28] , [31] , [32] , [40] . In our study, we used QPCR to quantitate viral loads in order to distinguish tumor-associated from incidental virus present in the lymphoma tissue section.…”

MHC haplotype frequencies in a UK breeding colony of Mauritian cynomolgus macaques mirror those found in a distinct population from the same geographic origin

“…Cynomolgus macaques are a valid and more readily available alternative to Indian rhesus macaques for use in non-human primate models of HIV infection. They have been used for many years (predominantly in Europe) in studies of pathogenesis [5,6,8,17,20,29], evaluation of antiretroviral therapy [3,9,15,32] and vaccine development [7,18,19,23,28,31]. Until recently, however, thorough characterization of cellular immune responses induced by infection or immunization with candidate vaccines has been limited due to a lack of information about MHC class I gene sequences in cynomolgus macaques.…”

HHV‐8/KSHV is Not Associated with AIDS‐Related Primary Central Nervous System Lymphoma

“…Second, the incidence of AIDS-KS and AIDS-PCNSL has decreased most profoundly compared to other AIDS-related cancers after the introduction of highly active antiretroviral therapy (HAART) (21). Finally, animal models infected with HIV homologs, but devoid of HHV8/KSHV infection fail to develop KS and PCNSL, although they frequently develop other types of AIDS-related cancers (14,31).…”