Researchers at the La Jolla Institute for Allergy & Immunology have shown that cytomegalovirus (CMV) in the salivary glands can be reduced -- and in some cases eliminated -- through the use of antibodies to enhance the disease-fighting power of the immune system. The research team's findings, based on controlled laboratory studies of mice, may also have implications for other chronic virus infections, such as hepatitis and HIV, the virus that causes AIDS.
CMV is a virus that affects the majority of the world's population, but produces little or no symptoms in healthy individuals. However, it can cause multi-organ disease in newborns or persons who are immuno-compromised such as organ transplant recipients or AIDS patients.
Ware said, "The main importance of these experiments is identifying the critical molecular targets controlling virus persistence, and two ways in which we can modulate immunity in vivo with the desired result of blocking virus spread to uninfected individuals.
"The potential excitement in the findings is that we may be able to one day use this kind of treatment in humans to block or significantly reduce the spread of cytomegalovirus and other chronic virus infections." Ware noted that the salivary glands are a primary source of transmission for many viruses due to sneezing, coughing and kissing. Eliminating the virus at this critical juncture may significantly reduce CMV's spread, he said.
In the study, Croft said the research team used an antibody to block the action of the IL-10 protein in the salivary glands of mice by inhibiting binding of IL-10 to its receptor. "IL-10 is a messenger molecule which suppresses the protective T cell response that would normally attack the cytomegalovirus," he said. "By blocking the ability of the IL-10 molecule to bind to its receptor, then you allow these T cells to do their job and reduce or eliminate this virus."
Croft said the scientists also tested a second approach, which used a stimulator antibody in mice to boost the action of the OX40 protein. OX40 helps T cells replicate more quickly, thus building the body's ability to more effectively battle the virus. "We used this approach to tip the balance in favor of the T cells that would reduce the virus," he said.
The scientists got a stronger result by blocking the IL-10 receptor. "It significantly reduced the virus load in all the animals and in 50 percent of them it completely eliminated it," Croft said. The OX40 treatment also greatly reduced the virus load, but did not eliminate it in any of the animals.
The findings of the Ware and Croft team parallel those of LIAI researcher Matthias von Herrath, M.D., who last year announced that he had successfully eliminated a chronic virus infection in mice by blocking the IL-10 receptor. "Dr. von Herrath's findings suggested that the IL-10 molecule plays a pretty important role in small RNA viruses, while our study looked at its impact in large DNA viruses," Ware said. "I think both of these studies lend credibility to the idea that the medical community should be looking at IL-10 as a molecular candidate that might be used to control persistent viral infections."
Ware and Croft's next step will be conducting animal studies with the IL-10 suppression and the OX40 enhancement combined into one treatment. "We tested them separately, but they may well be even more effective when combined," Croft said.
The team's findings were published online in the Journal of Experimental Medicine in a paper entitled, "Cytomegalovirus exploits IL-10-mediated immune regulation in the salivary glands." LIAI scientists Ian Humphreys, Ph.D., Carl Ware, Ph.D., and Michael Croft, Ph.D. led the study.
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