Attacking Cytomegalovirus With RNAi

Cytomegalovirus (CMV) is one of the herpesvirus group, viruses that are extremely hard or impossible for the body to clear. They lurk and return time after time. CMV doesn't cause immediate issues in healthy people, but over time it becomes one of the principle causes of the characteristic failure of the immune system with aging:

Your immune system is capped in its use of resources; it can only have a set number of T cells in operation at one time. ... chronic infections by the likes of cytomegalovirus (CMV) cause too many of your immune cells to be - uselessly - specialized. ... because you cannot clear it from your system, its presence chews up more and more of your limited immune resources with time.

Immune cells dedicated to remembering and attacking the many biochemical signatures of CMV are not available to fight new threats - and that starts to be a real issue in later life. Your immune system simply cannot mount an effective response when so much of it is tied up in uselessly awaiting the next emergence of CMV.

Many research groups are investigating ways to effectively destroy herpesviruses like CMV, and thus clear them from the body. As a strategy this might be compared to using metabolic manipulation to slow aging, insofar as (a) to have the best effect the methodology must be applied early in life, and (b) it's of little use to those already old. The damage is already done by the time you are old, and clearing out CMV doesn't do anything to free up the errantly specialized immune system resources.

A better strategy for reversing this immune system issue might be to use targeted cell destruction methods under development in the cancer research community to kill CMV-specialized immune cells and so free up space. There it doesn't matter that CMV is in your system, because the cull of specialized cells restores this aspect of your immune system to a more functional state. This type of treatment could then be repeated whenever necessary.

Like the mainstream of aging research, however, the bulk of work on CMV is focused on clearance (i.e. slowing the rate of damage) rather than immune system repair (i.e. restoration by removing damage). This is unfortunate, and yet another aspect of the most important debate over strategy in longevity science - do researchers continue to largely focus on slowing aging, or do they instead try to reverse and repair aging?

With that in mind, let me point out a recent paper on the use RNA interference to attack CMV by disabling its vital mechanisms - a strategy which you will notice is not all that different in complexity to the targeted cell destruction method mentioned above. Reversing aspects of aging and slowing aspects of aging will often enough require a similar level of resources to put into play, despite the fact that reversal is far more beneficial. This is why the choice of strategy is so important.

In order to develop a gene therapy to human cytomegalovirus (HCMV), RNA interference (RNAi) was employed to inhibit the expression of HCMV UL122 gene in vitro. ... it may be concluded that plasmids encoding siRNAs targeted to UL122 is able to in vitro reduce markedly the expression of [UL122].

Previous studies have shown that CMV without the UL122 gene is effectively disabled and cannot infect a host. This sort of work is very cutting edge, and it represents the beginning of the end for viruses as a threat to humanity. When medical technology and the research community can rapidly identify and disable lynchpin genes that are unlikely to rapidly evolve substitutes, then the common virus is pretty much out of luck.

This is all good news for those of us who intend a long and healthy life - the risk of death or serious illness due to pathogens will diminish greatly in the decades ahead. But for our generation, this sort of work is not the key to reversing the immune system damage we already suffer. We'll need a different approach there.

ResearchBlogging.orgDuan QJ, Tao R, Hu MF, & Shang SQ (2009). Efficient inhibition of human cytomegalovirus UL122 gene expression in cell by small interfering RNAs. Journal of basic microbiology PMID: 19810036

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