Source: La Jolla Institute for Allergy and Immunology

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Scientists

Make Important Finding On Cytomegalovirus Transmission

La Jolla Institute for Allergy and Immunology

May 11, 2007

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 Croft, Ph.D. led

the study.

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