Gammaherpesvirus infection and malignant disease in rhesus macaques experimentally infected with SIV or SHIV
| العنوان: | Gammaherpesvirus infection and malignant disease in rhesus macaques experimentally infected with SIV or SHIV |
|---|---|
| المؤلفون: | Scott W. Wong, Gregory Q. Del Prete, Claes Ohlen, Andrew C. Warner, Rebecca Kiser, Michael Piatak, Marshall Thompson, Vickie Marshall, Jeffrey D. Lifson, Yelena Golubeva, Jeremy Smedley, Denise Whitby, Rhonda MacAllister, Benjamin Holdridge, Jacob D. Estes, Xing Pei Hao, Vicky Coalter, Claire Deleage, Wendell J. Miley, Elaine S. Jaffe, Miriam R. Anver, Nazzarena Labo, Catherine Brands |
| المصدر: | PLoS Pathogens, Vol 14, Iss 7, p e1007130 (2018) PLoS Pathogens |
| بيانات النشر: | Public Library of Science (PLoS), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, RNA viruses, Fibrosarcoma, viruses, Simian Acquired Immunodeficiency Syndrome, Monkeys, medicine.disease_cause, Pathology and Laboratory Medicine, Macaque, Hematologic Cancers and Related Disorders, Immunodeficiency Viruses, Neoplasms, Medicine and Health Sciences, Gammaherpesvirinae, Rhadinovirus, lcsh:QH301-705.5, Immunodeficiency, Mammals, biology, Coinfection, Sarcomas, Eukaryota, virus diseases, Hematology, Animal Models, Herpesviridae Infections, Rhesus lymphocryptovirus, Viral Load, 3. Good health, Oncology, SIV, Experimental Organism Systems, Medical Microbiology, Viral Pathogens, Viruses, Vertebrates, Infectious diseases, Lymphomas, Simian Immunodeficiency Virus, Pathogens, Viral load, Research Article, HIV infections, Primates, lcsh:Immunologic diseases. Allergy, Herpesviruses, Immunology, Viral diseases, Research and Analysis Methods, Microbiology, Virus, 03 medical and health sciences, biology.animal, Virology, Old World monkeys, Retroviruses, Genetics, medicine, Animals, Molecular Biology, Microbial Pathogens, Biology and life sciences, Rhesus Monkeys, Lentivirus, Organisms, Cancers and Neoplasms, Simian immunodeficiency virus, biology.organism_classification, medicine.disease, Macaca mulatta, Tumor Virus Infections, 030104 developmental biology, lcsh:Biology (General), Amniotes, Parasitology, DNA viruses, lcsh:RC581-607, Viral Transmission and Infection |
| الوصف: | Human gammaherpesviruses are associated with malignancies in HIV infected individuals; in macaques used in non-human primate models of HIV infection, gammaherpesvirus infections also occur. Limited data on prevalence and tumorigenicity of macaque gammaherpesviruses, mostly cross-sectional analyses of small series, are available. We comprehensively examine all three-rhesus macaque gammaherpesviruses -Rhesus rhadinovirus (RRV), Rhesus Lymphocryptovirus (RLCV) and Retroperitoneal Fibromatosis Herpesvirus (RFHV) in macaques experimentally infected with Simian Immunodeficiency Virus or Simian Human Immunodeficiency Virus (SIV/SHIV) in studies spanning 15 years at the AIDS and Cancer Virus Program of the Frederick National Laboratory for Cancer Research. We evaluated 18 animals with malignancies (16 lymphomas, one fibrosarcoma and one carcinoma) and 32 controls. We developed real time quantitative PCR assays for each gammaherpesvirus DNA viral load (VL) in malignant and non-tumor tissues; we also characterized the tumors using immunohistochemistry and in situ hybridization. Furthermore, we retrospectively quantified gammaherpesvirus DNA VL and SIV/SHIV RNA VL in longitudinally-collected PBMCs and plasma, respectively. One or more gammaherpesviruses were detected in 17 tumors; generally, one was predominant, and the relevant DNA VL in the tumor was very high compared to surrounding tissues. RLCV was predominant in tumors resembling diffuse large B cell lymphomas; in a Burkitt-like lymphoma, RRV was predominant; and in the fibrosarcoma, RFHV was predominant. Median RRV and RLCV PBMC DNA VL were significantly higher in cases than controls; SIV/SHIV VL and RLCV VL were independently associated with cancer. Local regressions showed that longitudinal VL patterns in cases and controls, from SIV infection to necropsy, differed for each gammaherpesvirus: while RFHV VL increased only slightly in all animals, RLCV and RRV VL increased significantly and continued to increase steeply in cases; in controls, VL flattened. In conclusion, the data suggest that gammaherpesviruses may play a significant role in tumorogenesis in macaques infected with immunodeficiency viruses. Author summary Human gammaherpesviruses cause malignancies in HIV infected persons; in SIV infected macaques, gammaherpesvirus infections also occur. To understand the potential role of the rhesus gammaherpesviruses, RRV, RFHV and RLCV in cancers occurring in monkeys during SIV and SHIV studies spanning the last 15 years, we developed assays to measure the DNA viral load (VL) of each virus in these tumors and unaffected macaque tissues. We further characterized the tumors using immunohistochemistry and in situ hybridization, and quantified gammaherpesvirus DNA VL in PBMCs collected longitudinally during the original studies. We examined 18 animals with tumors and 32 controls. In all tumors, we detected one or more gammaherpesviruses; generally, one virus was predominant and very abundant compared to surrounding non-tumor tissues. SIV RNA VL in plasma and RLCV VL in PBMCs were independently associated with cancer risk. The longitudinal patterns of gammaherpesviruses VL, from SIV infection to death differed in cases and controls: while RFHV VL increased only slightly in all animals, RLCV VL and RRV VL increased significantly and continued to increase in cases, but flattened in controls. These data suggest that gammaherpesviruses may play a significant role in tumorogenesis in macaques infected with immunodeficiency viruses. |
| اللغة: | English |
| تدمد: | 1553-7374 1553-7366 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a4499b992fb1d24395f340021d9fcca http://europepmc.org/articles/PMC6042791?pdf=render |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2a4499b992fb1d24395f340021d9fcca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 15537366 |
|---|