Persistent Infection Harms Long Term Health and Life Expectancy

The decline of the immune system is an important component of aging, and one of the causes of that decline is persistent infection by common herpesviruses such as cytomegalovirus (CMV). This is near harmless in the short term, but over time more and more of the limited repertoire of immune cells are devoted to the futile attempt to clear out CMV - and ever less are left free to tackle other threats.

One possible solution is to destroy the CMV-specialized immune cells to free up space. This is a very plausible goal, given advances in targeted cell killing technologies emerging from the cancer research community. But here, scientists measure the cost of CMV infection in laboratory animals - more motivation for research groups that might be trying to build a therapy:

Persistent CMV infection has been associated with immune senescence. To address the causal impact of lifelong persistent viral infection on immune homeostasis and defense, we infected young mice systemically with HSV-1, murine CMV, or both viruses and studied their T cell homeostasis and function.

Herpesvirus(+) mice exhibited increased all-cause mortality compared with controls. Upon Listeria-OVA infection, 23-mo-old animals that had experienced lifelong herpesvirus infections showed impaired bacterial control and CD8 T cell function, along with distinct alterations in the T cell repertoire both before and after Listeria challenge, compared with age-matched, herpesvirus-free controls.

Herpesvirus infection was associated with reduced naive CD8 T cell precursors above the loss attributable to aging. ... To our knowledge, this study for the first time causally links lifelong herpesvirus infection to all-cause mortality in mice and to disturbances in the T cell repertoire, which themselves correspond to impaired immunity to a new infection in aging.


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