Measuring the Impact of Cytomegalovirus in Younger People

Cytomegalovirus (CMV) is one of the less immediately harmful members of the family of herpesviruses. It is very prevalent: most people have it in their system by the time they are old, but probably never even noticed, as the symptoms for a healthy individual are essentially nonexistent. Nonetheless like all herpesviruses CMV is very successful at remaining within the body after initial exposure, establishing a life-long infection despite the best efforts of the immune system to get rid of it. The recurring campaigns waged against CMV by your immune cells appear to have a long-term cost: we have evolved to support a given number of immune cells as adults, and as ever more of those immune cells become specialized to a specific pathogen, such as CMV, there is ever less space left in the inventory for cells that can tackle new threats or keep up with all the other jobs of the immune system, such as destroying precancerous and senescent cells.

If you eye the publications of an open access journal like Immunity and Ageing, you'll see a steady flow of papers looking at the role of CMV in age-related immune system decline, a fair-sized component of the frailty of old age. There are a range of possible approaches to this problem, but the most direct and potentially effective don't actually involve doing anything about CMV itself. Instead there are proposals to either add large numbers of new, fresh, and capable immune cells to the body or eliminate the CMV-specialized cells to free up space. Both of these approaches are quite near-term: only a a couple of years would be needed to develop a viable prototype therapy from where we are now, were a research group fully funded and tasked with the effort. Both the ability to culture immune cells and the ability to destroy specific cells in the body based on their surface markers are progressing rapidly.

Some research groups are working on a vaccine for CMV - but a successful vaccine won't do much good for those high percentage of adults in much of the world who have been infected for a long time. Their immune systems are already badly misconfigured as a result of the extended exposure. So tackling CMV isn't a good enough approach on its own, as it only stops the very slow pace of ongoing harm.

Here is a paper to suggest that the progressive disarray in the immune system caused by CMV starts early, even while young.

Rudimentary signs of immunosenescence in Cytomegalovirus-seropositive healthy young adults

Ageing is associated with a decline in immune competence termed immunosenescence. In the elderly, this process results in an accumulation of differentiated 'effector' phenotype memory T cells, predominantly driven by Cytomegalovirus (CMV) infection.

Here, we asked whether CMV also drives immunity towards a senescent profile in healthy young adults. One hundred and fifty-eight individuals (age 21?±?3 years, body mass index 22.7?±?2.7) were assessed for CMV serostatus, the numbers/proportions of CD4+ and CD8+ late differentiated/effector memory cells, plasma interleukin-6 (IL-6) and antibody responses to an in vivo antigen challenge (half-dose influenza vaccine). Thirty percent (48/158) of participants were CMV+.

A higher lymphocyte and CD8+ count and a lower CD4/CD8 ratio were observed in CMV+ people. Eight percent (4/58) of CMV+ individuals exhibited a CD4/CD8 ratio of less than 1.0, whereas no CMV- donor showed an inverted ratio. The numbers of late differentiated/effector memory cells were?~fourfold higher in CMV+ people. Plasma IL-6 was higher in CMV+ donors and showed a positive association with the numbers of CD8+CD28- cells. Finally, there was a significant negative correlation between [vaccine response and the levels of CMV particles present]. This reduced vaccination response was associated with greater numbers of total late differentiated/effector memory cells.

This study observed marked changes in the immune profile of young adults infected with CMV, suggesting that this virus may underlie rudimentary aspects of immunosenescence even in a chronologically young population.

Source:
https://www.fightaging.org/archives/2013/08/measuring-the-impact-of-cytomegalovirus-in-younger-people.php

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