Impact of Lifelong Cytomegalovirus Infection on Aging and the Immune System Focus of UA Research

The study, funded by a $2.3 million five-year NIH grant, is critically important to understanding how to improve older adults’ responses to vaccination against the infectious diseases that remain among the major causes of mortality of those over age 65.

A virus that infects us when we’re young and then hides in our cells throughout our lives without causing symptoms may weaken the ability of our immune system to defend  against influenza, West Nile or other viruses as we age.

How the cytomegalovirus (CMV) – one of the herpes viruses – impacts the aging of our immune system is being studied by researchers at the University of Arizona College of Medicine – Tucson, funded by a $2.3 million five-year grant from the National Institute on Aging/National Institutes of Health.

“It is critically important to understand the causes and consequences of lifelong CMV infection for immunity and aging. CMV is present in 70 to 90 percent of people over 65, which by 2050 will translate into 70 million people in the United States and more than 1 billion people in the world,” said Janko Nikolich-Žugich, MD, PhD, chairman of the UA Department of Immunobiology, co-director of the University of Arizona Center on Aging, Elizabeth Bowman Professor in Medical Research at the UA College of Medicine – Tucson, and a member of the UA BIO5 Institute. CMV has been associated with impaired immunity, increased morbidity due to cardiovascular diseases, and reduced lifespan and health span – the length of life spent in good health.

“Our research group recently showed that infection with only CMV, and no other acute or persistent viruses, causes defects in immune responsiveness to other infections and causes alterations in the naïve T cell receptor repertoire and impaired effector T cell responses,” said Dr. Nikolich-Žugich, principal investigator for the study, “Impact of CMV Upon T-cell Aging and Immune Defense.”

“But the precise mechanism by which CMV affects naïve T cell responses remains incompletely understood. Our study seeks to define the cost, if any, of persistent CMV infection on immune function as we age and to begin to define ways to intervene against the negative effects of CMV in aging.”

The adverse impact of lifelong CMV infection on the aging of T cells – a type of white blood cell essential to the functioning of the immune system – and the development of new immune responses could be due to a number of factors.

“Improved control of CMV and/or reduction of CMV-specific EM accumulation could be beneficial for immune defense, such as immune responsiveness to vaccination. But it is also possible that the virus actually helps the immune system in the younger age, while impairing it in older adults.”

UA researchers will assess the role of CMV in restricting T cell receptor (TCR) behavior and immune defense; the inhibition of protective immunity by CMV and/or by CMV-specific T cells; and whether improved control of CMV determines human immune responsiveness to vaccination.

Some people over age 65 control their CMV well and respond well to vaccines, such as the influenza vaccine, while others do not, noted Dr. Nikolich-Žugich.

“The immune system works hard to keep the dormant CMV in check. We hypothesize that efficient CMV control will correlate with strong and successful responses to vaccination in humans and that individuals who use vast resources to control CMV will be less likely to respond well to vaccination.”

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This research is supported by the National Institute On Aging of the National Institutes of Health under Award Number R01AG048021. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Thursday, October 16, 2014 - 14:40