Gammaherpesviruses linked to tumors in macaques with simian immunodeficiency virus

July 12, 2018, Public Library of Science
Rhesus lymphocryptovirus (RLCV) detection, using net generation in situ hybridization RNAscope (in red), in jejunum mass classified as Diffuse Large B-cell Lymphoma (DLBCL) in SIV infected Rhesus macaque. Scale bar 100μm. Credit: Whitby et al (2018)

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 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 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 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 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, Ph.D. "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".

Explore further: Gene-edited stem cells show promise against HIV in non-human primates

More information: PLOS Pathogens, DOI: 10.1371/journal.ppat.1007130

Related Stories

Gene-edited stem cells show promise against HIV in non-human primates

April 19, 2018
Gene editing of bone marrow stem cells in pigtail macaques infected with simian/human immunodeficiency virus (SHIV) significantly reduces the size of dormant "viral reservoirs" that pose a risk of reactivation. Christopher ...

Molecular culprit behind virus-mediated chronic inflammation and cancers identified

April 26, 2018
Within cells infected by Kaposi sarcoma herpesvirus (KSHV), the human protein CADM1 interacts with viral proteins to promote chronic inflammation, which plays a major role in the development of cancers caused by KSHV. Richard ...

Prior dengue or yellow fever exposure does not worsen Zika infection in monkeys

August 4, 2017
Rhesus macaques previously infected with dengue or yellow fever viruses appear to be neither more nor less susceptible to severe infection with Zika virus, according to new research published in PLOS Pathogens.

Rhesus macaque model offers route to study Zika brain pathology

June 21, 2018
Rhesus macaque monkeys infected in utero with Zika virus develop similar brain pathology to human infants, according to a report by researchers at the California National Primate Research Center and School of Veterinary Medicine ...

Zika monkey study suggests worse fetal effects for vaginal versus mosquito transmission

August 24, 2017
Rhesus macaques that were vaginally infected with Zika virus showed higher prevalence of Zika in the reproductive tract than previously seen in macaques that received skin injections of the virus. The findings, published ...

Study shows that certain herpes viruses can infect human neurons

December 4, 2015
For years, researchers have noted a tantalizing link between some neurologic conditions and certain species of the herpes virus. In patients with Alzheimer's disease, multiple sclerosis, and cerebellar ataxia, among other ...

Recommended for you

Researchers seek vaccine for 'traveler's diarrhea'

September 25, 2018
Every year, millions of people have vacations and business trips ruined when they succumb to "traveler's diarrhea" during their journeys. A major cause of traveler's diarrhea is bacteria called Enterotoxigenic E. coli, or ...

Experimental vaccine shows promise in preventing TB

September 25, 2018
(HealthDay)—Tuberculosis remains the most lethal of infectious diseases worldwide, killing more than 1.6 million people a year. But researchers say a new vaccine might prevent half of full-blown illnesses in infected people ...

Many doctors in India miss TB signs: study

September 25, 2018
Many private sector doctors in India miss the signs of tuberculosis and therefore provide patients inadequate treatment, according to a new study published Tuesday involving people hired to act out the symptoms.

New way of determining treatment for staph infections cuts antibiotic use

September 25, 2018
Using a clinical checklist to identify eligible patients, doctors were able to shorten the antibiotic duration for patients with uncomplicated staphylococcal bloodstream infections by nearly two days, Duke Health researchers ...

Breakthrough in designing a better Salmonella vaccine

September 24, 2018
UC Davis researchers announce in the Proceedings of the National Academy of Sciences this week a breakthrough in understanding which cells afford optimal protection against Salmonella infection—a critical step in developing ...

Antifungal agent found to be possible treatment for porphyria

September 24, 2018
A large team of researchers from Spain, France and the U.S. has found that a common antifungal agent might be useful as a treatment for a rare type of porphyria. In their paper published in the journal Science Translational ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.