Researchers Develop a Model for Kaposi’s Sarcoma Research

Newswise — In the month that marks the 25th anniversary of the first reported cases of AIDS in the United States, University of Virginia Health System researchers have published pioneering work describing a model system for long-term infection with a virus known as the Kaposi's sarcoma-associated herpesvirus (KSHV), which causes Kaposi's sarcoma (KS)—the most common AIDS-related cancer worldwide and the original harbinger of the AIDS epidemic in this country.

This work, led by Dr. Dean Kedes, associate professor of Internal Medicine and Microbiology, successfully recapitulated viral replication events within a mouse model system mimicking those observed in human patients, including infection of white blood cells with the expression of non-structural proteins promoting viral persistence, followed by increasing expression of structural proteins required for assembly of whole virus particles and spread of the infection. Addition of human immune cells to the model resulted in the production of KSHV-specific antibodies found in the serum of mice indistinguishable from those found in the serum of human patients infected with the virus and suffering from KS, according to the study published in the Journal of Clinical Investigation (http://www.jci.org).

The researchers also found that the antiviral agent ganciclovir successfully prevented the production of structural proteins by the virus, although it did not prevent initial infection of white blood cells. After the drug was stopped, viral replication resumed, supporting the contention that novel therapies are needed to treat and prevent this infection.

"I am very excited about these results and the new possibilities that this model opens to develop novel ways of preventing and treating the diseases caused by this human virus," said Dr. Kedes, a member of the University's Myles H. Thaler Center for AIDS and Retrovirus Research. The work was a collaborative effort between Dr. Kedes's laboratory, where Dr. Christopher Parsons spearheaded the work, and the laboratory of Dr. David Camerini, a former member of UVa's Department of Microbiology and now at the University of California, Irvine. The researchers will now use this model to study mechanisms by which KSHV enters host cells and manipulates the cellular machinery to cause tumors. Perhaps equally important, the model will allow for more effective preclinical testing of drugs designed to treat KSHV infection and KS.

To read the study, visit: https://www.the-jci.org/article.php?id=27249