Format

Send to

Choose Destination
PLoS Pathog. 2018 Jul 12;14(7):e1007130. doi: 10.1371/journal.ppat.1007130. eCollection 2018 Jul.

Gammaherpesvirus infection and malignant disease in rhesus macaques experimentally infected with SIV or SHIV.

Author information

1
AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, Maryland, United States of America.
2
Pathology/Histotechnology Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, Maryland, United States of America.
3
Laboratory of Pathology, Center for Cancer Research, NCI, Bethesda, Maryland, United States of America.
4
Vaccine and Gene Therapy Institute, Oregon Health & Sciences University, Beaverton, Oregon, United States of America.
5
Laboratory Animal Science Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, Maryland, United States of America.

Abstract

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.

PMID:
30001436
PMCID:
PMC6042791
DOI:
10.1371/journal.ppat.1007130
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center