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Forum URL: http://herpeshomepage.com/cgi-bin/dcforum/dcboard.cgi
Forum Name: Technical
Topic ID: 2533
Message ID: 10
#10, RE: I think you understand it fine.. ...and so do I.
Posted by BH on Oct-23-06 at 04:41 PM
In response to message #5
Hi C and Rajah,

I missed this post for a few days, and so did not add anything yet.

C, I think you are dead on in your interpretation of .....
"Holy S---! You mean the virus is this active?"

Yes, that is exactly what I mean. My research has not touched on this topic in a long time (since 1996), but lots of other people are still investigating this (Robert Hendricks in Pittsburgh, Lawrence Corey in Seattle, Diethilde Theil in Munich, and Georges Verjans in Rotterdam). When so many independent people all find the same thing, you can be certain that it is correct.

Theil's 2003 abstract illustrates the point well, that "latent" herpes infection is not completely latent at the molecular level.
Abstract here:

The basic idea is this.

When you get infected with herpes simplex virus, if the initial infection is enough for you to get recurrences, then chances are that you have about 1000 to 25,000 neurons in your body that harbor the latent virus (i.e., like an extra chromosome). That may sound like a lot of infected cells, but just remember that the number of cells in your body is greater than 10^12 (more than 1,000,000,000,000 cells make up your body).

To keep the math simple, let's say that you have exactly 10,000 latently infected neurons in your body....harbor viral DNA which is mostly silent.

If you look at the cells as a group, they are definitely latent.....nothing happening in 99.9% of those cells...pretty quiet on the whole. However, the picture that has been emerging for the past 10 years is that about once a week, one of those 10,000 cells actually leaves the "latent pool of cells" and starts making infectious HSV again. Most of the time this "single-cell reactivation event" is no big deal because your immune system does its job...no disease results, and precious little shedding of infectious virus occurs.

These low-level, single cell reactivation events occurring once per week are plenty to keep your immune cells busy, and thus when you look in the nerves that harbor "latent HSV" infection, there is a chronic low-level immune response.

Robert Hendricks' lab really found a smoking gun in 2003 when they showed that 70% of the T cells that chronically hang out in the latent nerves have T cell receptors that are specific for one small part of HSV...glycoprotein B. At random, your chances of finding a T cell with that particular receptor are like your chances of winning the $40 million powerball. The bottom line is that the virus has to be somewhat active in order for the T cells to hover so close to the infected neurons (within 1/100th of an inch of infected neurons).

So, the data says that herpes simplex virus and the immune system have "struck a deal" where the T cells can shut down full blown virus replication that would lead to disease, but the T cells can't figure out how to destroy the virus-infected neurons because the virus slips below the T cell's radar screen at the last second before the T cell gets really pissed (fully activated). In contrast, when you recover from the flu, your T cells nuke every influenza virus-infected cell in your body, because influenza has no such mechanism for entering "stealth mode."

Hope that helps a little.

- Bill