A model of lymphocryptovirus-associated post-transplant lymphoproliferative disorder in immunosuppressed Mauritian cynomolgus macaques

Immunocompromised individuals are at risk for developing lymphocryptovirus-associated lymphoproliferative diseases, such as Epstein Barr virus (EBV)-associated B cell lymphomas and post-transplant lymphoproliferative disorder (PTLD). We previously reported development of cynomolgus lymphocryptovirus (CyLCV)-associated PTLD in Mauritian cynomolgus macaques (MCMs) undergoing hematopoietic stem cell transplantation (HSCT), which mirrored EBV-PTLD in transplant patients. Here, we sought to develop a MCM model of lymphocryptovirus-associated lymphoproliferative disease in immunosuppressed MCMs without HSCT. Five simian immunodeficiency virus (SIV)-infected, CD8α+ cell-depleted MCMs received an infusion of autologous B-lymphoblastoid cells transformed with CyLCV, followed by varying degrees of immunosuppression. Four of five infused macaques developed masses coincident with increasing CyLCV plasma viremia, and necropsies confirmed the presence of multicentric lymphomas, which most commonly manifested in lymph nodes, gastrointestinal tract, adrenal glands, and pancreas. Affected tissues harbored neoplastic lymphocytes double-positive for CD20 and CyLCV EBNA2 antigen, large frequencies of proliferating B cells, and high levels of cell-associated CyLCV DNA. In addition, longitudinal 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) of one MCM successfully detected lymphoproliferative disease in the adrenal glands prior to clinical signs of disease. These data demonstrate successful induction of lymphocryptovirus-associated PTLD-like disease in 4 of 5 MCMs, and thus support the use of MCMs as a preclinical NHP model of EBV-associated lymphoproliferative disease that could be employed to test novel diagnostic and therapeutic modalities.

Authors

Institutions

Publication Details

Journal
PLoS Pathogens
Published
2024-11-11
DOI
https://doi.org/10.1371/journal.ppat.1012644
Citations
2
Primary Topic
Viral-associated cancers and disorders
Type
article
Field-Weighted Citation Impact
0.57

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

A model of lymphocryptovirus-associated post-transplant lymphoproliferative disorder in immunosuppressed Mauritian cynomolgus macaques

Jason S. Reed, Anne D. Lewis, Erik Mittra, Carla Boyle et al.
2 citations
PLoS Pathogens
Viral-associated cancers and disorders
0.57
article

A model of lymphocryptovirus-associated post-transplant lymphoproliferative disorder in immunosuppressed Mauritian cynomolgus macaques

Jason S. Reed, Anne D. Lewis, Erik Mittra, Carla Boyle, Jonah B. Sacha, Kimberly Armantrout, Michael K. Axthelm, Miranda Fischer, Sreya Biswas, Lois M. A. Colgin, Whitney C. Weber, Angela Panoskaltsis‐Mortari, Gabrielle Meyers, Mina Northrup, Courtney Waytashek, Amanda L. Johnson, Benjamin J. Burwitz, Rebecca L. Skalsky, Helen L. Wu, Christine Shriver‐Munsch, Richard T. Maziarz, Melissa R. Berg, Jeremy Smedley, Yan Chen, Jeffrey J. Stanton, Katherine B. Bateman, Helen Fisher, Tonya Swanson, John Templon
article en
2 citations

Abstract

Immunocompromised individuals are at risk for developing lymphocryptovirus-associated lymphoproliferative diseases, such as Epstein Barr virus (EBV)-associated B cell lymphomas and post-transplant lymphoproliferative disorder (PTLD). We previously reported development of cynomolgus lymphocryptovirus (CyLCV)-associated PTLD in Mauritian cynomolgus macaques (MCMs) undergoing hematopoietic stem cell transplantation (HSCT), which mirrored EBV-PTLD in transplant patients. Here, we sought to develop a MCM model of lymphocryptovirus-associated lymphoproliferative disease in immunosuppressed MCMs without HSCT. Five simian immunodeficiency virus (SIV)-infected, CD8α+ cell-depleted MCMs received an infusion of autologous B-lymphoblastoid cells transformed with CyLCV, followed by varying degrees of immunosuppression. Four of five infused macaques developed masses coincident with increasing CyLCV plasma viremia, and necropsies confirmed the presence of multicentric lymphomas, which most commonly manifested in lymph nodes, gastrointestinal tract, adrenal glands, and pancreas. Affected tissues harbored neoplastic lymphocytes double-positive for CD20 and CyLCV EBNA2 antigen, large frequencies of proliferating B cells, and high levels of cell-associated CyLCV DNA. In addition, longitudinal 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) of one MCM successfully detected lymphoproliferative disease in the adrenal glands prior to clinical signs of disease. These data demonstrate successful induction of lymphocryptovirus-associated PTLD-like disease in 4 of 5 MCMs, and thus support the use of MCMs as a preclinical NHP model of EBV-associated lymphoproliferative disease that could be employed to test novel diagnostic and therapeutic modalities.

PLoS PathogensVol. 20(11)
Oregon National Primate Research Center (US), Minneapolis Institute of Arts (US), Oregon Health & Science University (US), Society of Nuclear Medicine and Molecular Imaging (US), University of Minnesota System (US), Cancer Institute (WIA) (IN), University of Minnesota Medical Center (US), OHSU Knight Cancer Institute
amfAR, The Foundation for AIDS Research, Amgen, Bristol-Myers Squibb, Gilead Sciences, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, ViiV Healthcare, National Institutes of Health, Oregon National Primate Research Center, NIH Office of the Director, Office of Research Infrastructure Programs, National Institutes of Health
Good health and well-being
Openalex Percentile: Top 27%
Viral-associated cancers and disorders
0.57
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.