Portuguese researchers are reporting that they have created a chimera virus that allows the study of molecules to treat cancers caused by human herpes virus infection in mice models of disease. They report in the journal Plos Pathogens that chimera viruses may be able to disable lymphomas, paving the way for new treatments.
There are several types of herpes viruses that infect humans, such as herpes simplex, chickenpox, cytomegalovirus, Epstein-Barr, and Kaposi sarcoma herpesvirus (KSHV). One of the main characteristics of herpes viruses is their ability to infect their hosts for life. In a small percentage of these individuals, these infections can lead to cancer.
However, cancers associated with Kaposi virus infection have an Achilles heel—the tumor cells' viability is directly dependent on the survival of the Kaposi virus. Now, it may be possible to cripple it by manipulating a specific protein.
Researchers at Harvard Medical School collaborated with scientists at the Instituto de Medicina Molecular Lisboa and examined a protein called LANA. This protein is part of the Kaposi virus and it is vital for maintaining infection. Without LANA, the virus loses its ability to cause cancer, according to the researchers.
The team found that when LANA is cloned into a virus similar to Kaposi, which infects mice instead of humans, it preserves its functionality. This finding came as a surprise since it was assumed that as a consequence of the evolutionary divergence between human and other animal viruses, the genes that code for LANA could not be switched.
The researchers discovered that even though there are more than 60 million years of divergence between the human KSHV and its rodent homologue, LANA's functional mechanisms are preserved.
“We were very surprised when the experiment worked since there are more than 60 million years of evolutive divergence between the two viruses. The human cancer virus, KSHV, has a protein, LANA, that it depends on for its survival and we found that we can now study this protein in a mouse model of virus infection by substituting the KSHV LANA into the mouse virus,” said Kenneth Kaye, MD, an associate professor of medicine at Harvard Medical School, Brigham and Women's Hospital in Boston, Massachusetts.
The researchers hope they have created a chimera virus that may change the future of how lymphomas are treated. It is a mouse virus with a human viral gene that can be used to test molecules that inhibit human LANA protein in an animal model of disease. Ultimately, this could lead to new ways of treating human herpes virus infection and its associated cancers.
“Since we can now study this KSHV cancer virus LANA protein in mice, it will be possible to test future therapies directed against this virus protein, which is essential for tumor cells to grow,” Dr. Kaye told OncoTherapy Network.