Nestled safely away within your cells, among your DNA, lies something…foreign. An invader. Something you weren’t born with, hidden, evading your immune system and waiting to make its next strike: a ‘latent’ virus.
In all probability, there are armies of different viruses performing this same trick throughout your body. Remaining silent; some of their own mysterious accord, others kept in check by your immune system or by random mutations, rendering them useless.
Now researchers at The Ohio State University and the University of Oxford have worked out how some of these viruses can reactivate in healthy people, and once again go about their nefarious mindless deeds: hijacking our cells machinery, producing more of their own kind, and causing disease.
An inefficient virus kills its host. A clever virus stays with it. — James Lovelock
In healthy people latent viruses aren’t generally a problem, occasionally annoying, but rarely life threatening. However, if your immune system has been compromised—by leukaemia or immunosuppressant drugs for example—the story is different. The viruses may emerge again and, unchecked by the immune system, go out of control. This is why we need to understand how viruses leave—or can be kept in—their latent states, where they are no trouble, so we can predict and control it.
Following your first exposure to a virus like HSV-1—the cold sore virus—for example, you suffer the initial infection which, thankfully, starts to heal, but the virus hasn’t gone.
Your immune system hasn’t eradicated it—though ‘memory T-cells’ now ‘know’ it—the virus has merely retreated along a nerve, the trigeminal ganglion, in your face where it hides. Everything needed to make a new virus is right there, filed away in the nerve cells nucleus, alongside your own DNA.
From some signal, some opportunity, HSV-1 kicks back into action, producing viral particles and sending them down the nerves length to the lips, where they start to form the blisters characteristic of a cold sore, in an attempt to go on and infect others. This basic story is much the same for other viruses that also lay dormant within with your cells.
The Ohio and Oxford University teams noted that infection with the CMV virus (a member of the Herpes family) produces large numbers of an immune cell called a ‘memory T-cell’ specific for CMV. The team also note that a sub-type of these called ‘killer T-cells’seem to be needed to control acute infections by CMV.
Latent CMV infection, unchecked, may eventually go on to cause cancer or other diseases. This is much the same as many other latent viruses, such as herpes zoster, normally dormant in nerves near your spinal chord, but occasionally goes on to cause shingles. Understanding what affects virus specific memory T-Cells, and therefore the activity of latent viruses, could be hugely important for preventing cancer and other viral diseases, as well as their transmission to uninfected people. This is especially important for both those caring for and those with compromised immune systems, such as bone marrow, or other, transplant patients.
The investigate the team infected mice with a form of CMV (mCMV) and waited for the virus to become latent. They then measured the number of memory T-cells specific for mCMV, in the mouse’s lungs, where mCMV primarily infects the mice.
Once they were confident the infection was now latent, part of a bacterial cell wall, called LPS was injected. The LPS tricks the mouse’s immune system into thinking that it was under bacterial attack, prompting a strong immune response against it. The team had previously shown that this caused reactivation of latent mCMV, but they couldn’t be certain why.
The number of mCMV memory T-cells in the lungs dropped, but there was no drop in other types of T-cells. The level of mCMV RNA, a measure of the amount of ‘latent’ virus, was also measured and started to go up, indicating that the mCMV was becoming more active. By the time that the mCMV memory T-Cells were returning to normal, the mCMV RNA had begun to drop again.
This seems to indicate that the body directs resources away from latent infections somehow—while maintaining a kind of equilibrium of T-cell numbers—to deal with the more immediate immune or infection dangers. This, in turn, gives the latent viruses just the opportunity they’ve been waiting for; becoming an active infection again.
Though the T-Cells can’t eradicate the infection, they do seem to be able to keep it in check somehow, applying the brakes and preventing it spreading, while allowing the host cell to keep working, more or less, as normal.
As is often the case, this is early stage work, and may not apply to humans. That being said, there is also a good chance it does, so it merits further investigation, and adds to what we already know about regulation of latent viruses.
The Ohio and Oxford teams work seems to compliment other hypotheses about how latent viruses are kept in check. For example, chemical modifiers are though to be added directly to the viral DNA (“epigenetic changes”), which act as an ‘off switch’ preventing the DNA ever being used. But, again, how this happens and is regulated is poorly understood.
Anything which helps us understand how viruses behave in our bodies, and how our bodies respond to them, could be hugely useful not just for treating but also preventing disease, and this study is one more small step in that direction.
Reference: Campbell, J. et al., 2012. Transient CD8-memory contraction: a potential contributor to latent cytomegalovirus reactivation. Journal of leukocyte biology, 92(November), pp.933–937. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22730545 [Accessed November 2, 2012]. ($$)
A big thanks to Cyan Jenkins for letting me use her excellent illustration as the cover image for this post. She’s got a great, fun and unique style. Hire her here: www.Cjenkinsart.blogspot.com