Viruses known as gammaherpesviruses may raise
the risk of cancer in macaques infected with Simian Immunodeficiency
Virus or Simian Human Immunodeficiency Virus (SIV/SHIV), according to
new research published by Vickie Marshall of the Frederick National
Laboratory for Cancer Research, Maryland, and colleagues.
In humans infected with HIV, the gammaherpesviruses known as Epstein
Barr Virus (EBV) and Kaposi's Sarcoma-Associated Herpesvirus (KSHV) are
associated with development of lymphomas and other cancer types.
Macaques used in research as animal models of HIV infection can also
experience gammaherpesvirus infection, but the role of these viruses in
cancer development in the animals is poorly understood.
To help clarify this role, Marshall and colleagues developed new
techniques to test for gammaherpesvirus DNA in tumor samples from 18
macaques that were infected with SIV/SHIV from 2001 to 2015 as part of
studies conducted by the national laboratory's AIDS and Cancer Virus
Program. They compared these results with samples of healthy, non-tumor
tissue from the same animals, as well as samples from 32
SIV/SHIV-infected macaques that did not develop tumors.
The researchers found at least one rhesus gammaherpesvirus in all but
one of the tumors they studied. In most of the tumors, one of the three
rhesus gammaherpesviruses -- known as RRV, RFHV, and RLCV -- was
predominant and was present in significantly larger amounts than in
nearby non-tumor tissue.
Analysis of viral DNA in blood samples from all 40 animals showed
that RLCV was associated with cancer risk. Blood samples taken
periodically between SIV infection and death revealed different patterns
of gammaherpesvirus abundance in healthy animals versus those with
tumors. In all of the animals, RFHV levels increased slightly over time,
but in those with tumors, RLCV and RRV levels increased significantly
and continued increasing over time, while levels flattened in the
healthy macaques.
While these results do not confirm whether gammaherpesviruses
directly cause cancer in SIV/SHIV-infected macaques, they strongly
suggest that the viruses contribute to tumor development in the animals.
Since these tumors have characteristics in common with HIV-associated
tumors, further study of gammaherpesviruses in SIV/SHIV-infected
macaques could help improve understanding of HIV-associated tumors and
potential new treatment approaches.
"Cancer caused by oncogenic viruses are a substantial cause of
morbidity and mortality worldwide especially in people living with HIV,"
said lead author Denise Whitby, PhD. "Our study emphasizes the utility
of non-human primates naturally infected by gammaherpesviruses and
experimentally infected by SIV as a tool to study the pathogenesis and
potentially treatment of such cancers."
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